Listing of Public Comments on
Proposed Adoption and Implementation of the Eighth Edition of the
Guide for the Care and Use of Laboratory Animals

Entire Comment Period: 02/24/2011 - 05/24/2011

In a February 24, 2011 Federal Register Notice (PDF - 58 KB), NIH requested public comments on:

  1. NIH’s adoption of the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals and
  2. NIH’s proposed implementation plan which would require that institutions complete at least one semiannual program and facility evaluation using the eighth edition of the Guide as the basis for evaluation by March 31, 2012.

The original comment period was scheduled from February 24, 2011 to March 24, 2011. (See NOT-OD-11-042.) This comment period was extended twice, on March 18, (See NOT-OD-11-056.) and April 21. (See NOT-OD-11-066.) Ultimately the comment period spanned 90 days, closing on May 24, 2011. In addition to the time extension, the NIH removed the original 6,000 character limit on the comment form fields in the April 21 extension to maximize the opportunity for individuals and organizations to provide comments to NIH.

NIH received a total of 806 comments from Assured institutions, professional organizations, animal advocacy organizations, and individuals. Duplications (7) and comments that were not relevant to issues requested in the Federal Register (2) were removed from the database, leaving 797 comments. Some comments were relevant, but did not address the issues of adoption and implementation of the Guide. These included discussion of rulemaking requirements, comments on the Guide committee selection process, conflicts of interest, requests to extend the public comment period, and requests to remove the character limit on submissions. These comments remain in the database.

600 comments were received from those who identified themselves as individuals. 32 comments identified as official correspondence from Assured institutions were received. (On May 24, 2011, there were 1,030 Assured institutions.) 24 comments were submitted by professional organizations and 4 comments were submitted by animal advocacy organizations. A total of 137 institutions and organizations were represented in the database. A total of 276 comments appear to have originated from form letters authored by 4 organizations or individuals.

Names of individuals were redacted from the comments; the symbol “*****” replaces personally identifiable information.

ID Entry Date Affiliation Organization
Name
Organization
City and State
Comments
1 02/24/2011 at 03:50:33 PM Self     Comment 1:
I think this is a well-thought out, extremely well researched document. I think it will serve the laboratory animal community well to adopt it in full. As with any major revision, there will be some grumbling and complaining about making changes. However, I think that the changes benefit the animals and will add to the credibility of animal care and use programs.

Keep in mind OLAW may need to issue some position statements like AAALAC has done regarding some of the more controversial issues contained in the Guide.


Comment 2:
This sounds like a reasonable time frame.

2 02/24/2011 at 04:39:35 PM Self     Comment 1:
This seems like a reasonable plan given the flawed process that led to the new 8th Edition. There are many problems with this Guide and some changes and new or renewed rules are without scientific or even empirical merit. The list of persons and organizations that were prohibited form serving on the Guide's revision committee gives reason for pause. The new edition is going to cause more confusion and cost than it is going to increase animal and human well being. The animal rights movement must be quite pleased.

Finally what alternative does PHS have to accepting the 8th Edition?


3 02/24/2011 at 06:01:50 PM Self     Comment 1:
I am in favor of NIH adopting this edition of the Guide as a basis for evaluation of institutional programs. However, NIH should also consider using the FASS "Guide for the Care and Use of Agricultural Animals in Research and Teaching" as an additional reference document for larger species that have limited covreage in the "Guide for the Care and Use of Laboratory Animals (Guide)"


4 02/25/2011 at 12:33:12 AM Self     Comment 1:
This updated edition of the Guide seems very thoughtfully considered, and I thank the Committee for all their hard work and dedication.

I offer only two recommendations relating to past tragedies at my own institution:

Requirements for automated environmental monitoring must be updated given the increasing availability of low-cost technological solutions. Automated temperature monitoring and alerting must by now become mandatory for most facilities rather than merely recommended. As stated in OLAW's FAQ, "Sole reliance on employees to identify changes in animal room conditions or the use of high-low thermometers to track changes in temperature may not be sufficient to allow timely intervention and prevent catastrophic loss."

In addition, video surveillance should be considered not only for building security, but also to facilitate independent oversight of animal housing conditions and help ensure that experimental procedures follow approved protocols.


Comment 2:
NIH extramural research programs are themselves institutional programs receiving Public Health Service support for activities involving animals, and must comply with the same federal principles expected of individual grantees.

NIH has placed the burden of applying the "Three Rs" squarely upon individual researchers, while neglecting these principles entirely in decisions of funding. Given multiple proposals of comparable merit as scored by expert scientific review groups, NIH currently gives zero weight to differences in the numbers and types of animals used, or the relative levels of pain and distress that would be caused by the proposed experimental methods.

No implementation plan will be adequate that exempts the NIH administration itself from its responsibility to apply the ethical principles described in the Guide to all decisions determining which animal experiments or alternative studies will be supported by taxpayer funds.

5 02/25/2011 at 02:10:54 PM Organization IACUC, University of Virginia Charlottesville, VA Comment 1:
I would like to thank the "Committee to Update the Guide for the Care and Use of Laboratory Animals" for its thoughtful and thorough undertaking in updating and comprehensively making additions to the 2010 "Guide." This was undoubtedly a daunting challenge for which you are all to be commended.

Our Institutional Animal Care and Use Committee has reviewed the pre-publication version of the 2010 "Guide" and would like to express our concerns on only two changes. One change we feel will adversely impact the biomedical research community, and on the other hand proposes something that is at odds with experts in human medicine.

The first issue pertains to the need to provide a female mouse with litter 50 sq. in. of cage floor space (page 62). Currently the most common type of mouse caging at our institution is a small shoebox that has a floor space of 75 sq. in. allowing housing five adult mice similar, I'm certain, to many other institutions. The caging industry has built the small shoebox cage to this floor size standard based upon the 1996 "Guide." The most common mouse breeding scheme at our institution is the polygamous trio harem of one male and two females established to maximize rodent production by taking advantage of the post-partum estrus and the cross-fostering of litters by two resident lactating females. Our IACUC's concern regarding overcrowding in harem breeding cages led to our policy that states "no more than 12 pups when the older of two litters reaches 12 days of age".1 This requires one pregnant prepartum female be removed when large litters are the result of this mating. But given that the vast majority of our mouse colonies are genetically-engineered mice (GEMs) with a propensity to have small litters, similar to many inbred strains of mice, we have anecdotal evidence that the presence of two lactating females increases the probability of offspring maturing to weaning; the reproductive success at weaning being our measure of the well-being of the offspring. To our knowledge there is little evidence in the literature of GEM offspring well-being adversely impacted by trio breeding. If this requirement is implemented it would cause a substantial increase in the number of shoebox cages we currently would have to maintain and impact the mouse space available to support our current research programs.

However, given the current language in Table 3.2 of the new "Guide" all trios would be required to be separated precluding the possibility of cross-fostering of small litters. I ask that you consider removing this space requirement for female mice with litters from the 2010 "Guide" and allow each institution to develop a policy similar to our own (attached).

The other issue our IACUC feels should be re-examined is the requirement for oxygen sensors in animal magnetic resonance imaging areas where cryogenic gases are used (page 157). The literature sited for this requirement appears in the ILAR Journal.2 We respect the opinion of the authors but find them at odds with the American College of Radiologists (ACR) Guidance Document for Safe MR Practices: 2007.3 The ACR guidance document specifies cryogen emergency vent locations and pathways, and specifically states on page 12, "It should be pointed out that room oxygen monitoring was discussed by the MR Blue Ribbon Panel and rejected at this time because the present oxygen monitoring technology was considered by industry experts not to be sufficiently reliable to allow continued operation during situations of power outages, etc." When a significant cryogen quench occurs that would decrease room oxygenation the room rapidly fills with fog, the location of the exhaust vent away from the exit door, signage stating to exit the room when this occurs and appropriate vent piping and placement of the discharge point are the most important safety factors according to the ACR. Our IACUC further feels that specifying the use of non-ferrous compressed gas tanks around MR scanners rather than remote storage would seem prudent.

I hope the committee will consider our IACUCs collective opinion with regard to these two new requirements of the 2010 "Guide." We feel it our responsibility to inform the Committee to Update the Guide for the Care and Use of Laboratory Animals of our sentiments.

Sincerely yours, William Sutherland, PhD Professor of Cell Biology Chair, Institutional Animal Care and Use Committee University of Virginia

1. ReebWhittaker et al. 2001. Laboratory Animals 35:5873 2. Klaunberg BA, Davis JA. 2008. ILAR J 49:4-16. 3. E. Kanal et al. 2007. AJR 188:1–27


Comment 2:
POLICY ON BREEDING AND WEANING OF RATS AND MICE Federal regulations establish the density of animals permitted in rodent cages. Breeder rats and mice and their litters can occupy considerable cage space, produce large amounts of fecal and urinary material, and increase cage temperature, humidity, and ammonia levels, all of which can create unhealthy conditions. When litters of two different ages are present in the same box, the younger litter often receives insufficient milk. Finally, the presence of more than one male in a breeding cage often results in aggression between competing males and fetal resorption (Bruce effect).

The following standards provide allowable densities and age/sex combinations to be applied to mouse breeding cages. Special exemptions to these standards can be made that improve animal well-being, such as to accommodate weanlings of low birth weight, slow growth rates, or insufficient mothering; a typical solution might be to cross-foster to other females in the cage. Requests for ongoing exceptions for particular strains should be submitted to the ACUC by revision of your animal use protocol, in the Main Procedure section under a heading "Request for Exception to the Breeding and Weaning Policy". Exceptions must be justified by providing published citations or PI data demonstrating post-natal failure-to-thrive of the strain in question. Potential reasons for exemption(s) include: 1) Experimental design (e.g. studying psychological imprinting of pups); 2) Need to extend suckling in strains that fail to thrive (requires supporting data); 3) Need to prevent cannibalism diminished by cross-fostering (requires data).

BREEDING SCHEMES AND LITTER NUMBERS ALLOWED: •No more than one adult male is allowed in a breeding cage. •Female rodents must be at least 6 weeks old before they are placed in a breeding cage with a male who is greater than 10 weeks of age. The only exception to this is superovulation of 3-4 week old female mice for collection of zygotes or embryos. •A cage is considered overcrowded if a new litter is born before the older litter from the same female is weaned, or if the older litter remains with the female beyond 23 days of age. Litters with ? 4 pups do not require weaning separation if the male is removed during pregnancy. •Weaning beyond 23 days (25 days of age if CCM does it) is reserved for strains that have litters that routinely fail-to-thrive. In such cases, the male, or even better the pregnant female must be removed from the cage when either female is obviously pregnant (e.g. by 12 days gestational age). Note: Late weaning of this sort requires a special exemption as defined below to avoid ACUC censure.

Animal caretakers are responsible for recording birth dates for litters on cage cards, however they may be recorded by research staff as well. A. One male x one female: Litters should be weaned by post-natal Day 23, or before birth of another litter, whichever is first. Animal care technicians will automatically wean each litter by post-partum Day 25, or whenever a new litter is born, if investigators have not already done so. Investigators will be charged for this service. If there is no prior arrangement with the CCM staff to wean for the PI, it will be considered a non-compliance issue by the ACUC. B. One male x two females: If breeding is conducted in a 1:2 ratio, it is recommended that one of the two females be removed to a separate cage when observed to be pregnant*. Alternatively, it is permissible to keep the male, two females, and the pups together provided that when the oldest litter reaches 12 days of age there are no more than 12 pups in the cage (combined). This is based upon standards used at the Jackson Laboratory (Reeb-Whittaker et al, 2001, Laboratory Animals 35:58-73). Weaning must still be accomplished by Day 23. The animal care technicians will wean litters at Day 25 if not already done by the investigators, and investigators will be charged for this service. If there is no prior arrangement with the CCM staff to wean for the PI, it will be considered a non-compliance issue by the ACUC. C. One male x three or more females: If more than two females are housed with a male for breeding, pregnant females (e. g. 12 days gestational age*) must be separated into boxes containing no more than two pregnant females before any delivery, and the 1:2 policy above ("B.") is then followed. If removal of obviously pregnant females in this breeding scheme is not done by the research staff, the animal care technicians will perform this function and investigators will be charged for this service. If there is no prior arrangement with the CCM staff to wean for the PI, it will be considered a non-compliance issue by the ACUC.

The accepted procedure for post-Day 25 day weaning: Occasionally, litters (or individuals in a litter) do not thrive or there may be other extenuating circumstances to justify delayed weaning. If you feel a litter (as defined in this policy) is not ready to be weaned, consult your vivarium supervisor. Each supervisor has the authority to provide a one-time exemption (one cage, or for concurrent cages of a new strain) delaying weaning up to 9 days in length for any specific litter (normally weaned on Day 23, extension to 32 days maximum). If a new litter is born to another female in the cage during the exemption period, it must be removed with that dam to another cage, if the original exempted litter cannot be weaned. Permission for ongoing weaning age exemptions for a particular breeding line must be obtained from the ACUC by submitting a protocol modification for that strain. Note: during any delayed weaning situation, the male must be removed from the cage when either female is obviously pregnant (e.g. by 12 days of gestation) to avoid post-partum estrus breeding.

6 02/28/2011 at 01:47:21 PM Self     Comment 1:
give extra time to comment. please send me a complete copy of the eigth so i can comment more fully. i have lost respect for the avma, which seems to be all about profit and money rather than any humane treatment of any animal. their decision that its ok to put newly born chicks into a woodchipper to kill them shows just how bad this group is - they are human pond scum as far as i can see if they believe this is ok.

the lab animals never end up alive. they are always killed. i find that unacceptable. the secrecy in how these grants are awarded is beyond belief. the public never never ever finds out whare their tax dollars are going. this is undemocratic. this is secret corruption and needs to be changed. all grants for any research of any kind needs to be totally open to the publc. pictures must be taken to show care and treatment of any animal. the pbulic must be allowed inside the labs to view the animals being abused in labs. jall animals used in any lab experiment needs to be put on the web with the followin ginformation on the lab where it is taking place. each animal individually must be listed. for example dog, white age 5 years test - skin duration - expected result validity NO ANIMAL SHOULD BE USED WITHOUT THIS NIFORMATION BEING QUICKLY AVAILABLE TO THE PUBLIC. THE NAME OF THE PUBLIC MEMBER OF THE IACUS MUST BE CLEARLY PUT ON LINE SO THAT THEY CAN BE QUICKLY FOUND AND COMMUNICATED WITH. ANY ANIMAL USED IN RESEARCH WORK THAT IS KEPT ALIVE NEEDS TO HAVE A RETIREMENT SUM OF MONEY PUT ASIDE TO CARE FOR THAT ANIMAL FOR THE REST OF ITS LIFE. IN FACT, EVERY RESEARCH ANIMAL SHOULD HAVE A TAX PUT ON IT TO ESTABLISH SUCH RETIREMENT FUNDS. I SUGGEST AN INITIAL TAX OF $1,000 ON EACH ANIMAL USED IN RESEARCH TO GO INTO THE FUND TO TAKE CARE OF ANIMALS THAT LIVE AFTER RESEARCH TESTS. ALSO, I PROPOSE THAT ALL LAB ANIMAL TESTS BE DISCONTINUED AND BANNED HENCEFORTH. I DO NOT BELIEVE THE TESTS THAT ARE GOING ON ARE VALID IN ANY WAY TO BE INTERPRETED FOR ANY HUMAN BENEFIT. THIS IS ALL ABOUT GREED AND MONEY. TESTING ON ANIMALS STARTED IN 1500 AND WE HAVE MUCH MORE MODERN, MORE ACCURATE METHODS THAN THIS TO USE TODAY. JEAN PUBLIC ADDRESS IF REQUIRED.


7 02/28/2011 at 03:14:47 PM Self     Comment 1:
The new Guide was based largely upon perception rather than science. Several things in the guide are actually harmful to animals. For example the group housing is the default for all species. This is contraindicated in a number of conditions. Rabbits fight when housed together. Large animals, such as pigs, when group housed post surgically will cannibalize less dominant pigs if the incision is bloody. For behavioral studies rodents have changed behavior when group housed. There is not any scientific evidence that changing the height of rabbit cages from 15 to 16 inches has any positive effect on animal welfare. The new guide is voluminous and will require a great deal of effort on the part of the research community to determine how to be in compliance with the numerous vague sections. This guide should be thoroughly reviewed and rewritten from its present form and content.


Comment 2:
I do not believe that institutions will be able to even determine proper procedures and protocols for reviewing facilities under the new guide within a year. Several organizations such as AAALAC and AALAS have been struggling to make comparisons and develop guidelines for compliance since last summer. There are not any training programs scheduled to train institutions in compliance issues with the new standards.

8 02/28/2011 at 05:43:15 PM Self National Jewish Health Denver, Colorado Comment 1:
The 8th edition of "The Guide" should NOT be adopted for the following reason:

On page 57 of "The Guide", Table 3.2 lists recommended minimum cage floor space per mouse. The only change from the 7th edition is that breeding triads are not allowed in standard shoebox (77sq. inches) cages because a single female with a litter should have at least 51 sq. inches of space. The maximum recommended number of adult (>25 g) mice per shoebox cage remains at 5.

However, I could find no scientific basis for these recommendations. In fact, the references cited on p. 58 with regard to cage space argue, if anything, that for many strains, more mice can be housed per cage than the minimum currently recommended by the 7th edition (Davidson Comp. Med. 57:355, 2007; Smith et al. Comp. Med. 54:656, 2004; Gonder and Laber ILAR J 48:29, 2007; Smith et al. Comp. Med. 55:368, 2005.

One of these shows that C57BL/6 mice, housed at 10 per shoebox cage, are as healthy as those at 5 per cage. Another reference provides evidence of anxiety disorder in mice that are not sufficiently crowed.

Therefore, on the basis of the science cited by the authors of "The Guide", I believe that breeding traids should be allowed and that the minimum amount of space per mouse should be doubled over the current space specified by the 7th edition, with the usual footnote that more space may be required for some strains or in special circumstances.


9 03/01/2011 at 03:46:39 PM Self     Comment 1:
The guide states that pharmaceutical grade chemicals or substances should be used when available for studies conducted in animals to ensure that toxic or unwanted effects are not introduced into studies. I have difficulty with this suggestion. First, the assumption that toxic or unwanted effects occur to any significant extent because of the use of non-pharmaceutical grade chemicals or substances in animal studies appears unwarranted. Currently, pharmaceutical grade chemicals or substances are only rarely used in animal studies, and I am unaware of any problems associated with this practice. Is there any empirical evidence of such a problem? How frequently do such problems occur? Second, there are problems of definition. In particular, what is meant by pharmaceutical grade is unclear. This could be taken to mean that it is more desirable to crush tablet formulations of medications and inject these ip than to prepare a solution using a substance obtained from a chemical company. Clearly, this is not desirable. Finally, that a pharmaceutical grade compound is unavailable can be difficult to demonstrate depending upon the definition of pharmaceutical grade. If this is defined by compound purity or the like, then such compounds can be custom synthesized in almost all cases, but at a significant cost in time, effort and financial resources. This would is a burdensome guideline, if as seems likely to be the case the problem being addressed cannot be reliably demonstrated.


10 03/02/2011 at 01:02:16 PM Organization Mayo Clinic Rochester MN Comment 1:
The mouse housing conditions for breeding that have been recommended (Table 3.2 and associated text) disregard natural mouse reproductive behavior, and will have negative consequences for mouse social living. The guide states that professional experience is the basis for the new requirements, but also states that scientific studies that have been performed were not used to generate the new rules. The fact remains that mice live in harems in the wild. They also live in nests in which many individuals occupy a limited space. But now without scientific basis, this new guide has purposely put forth new rules whose end result will be to make mouse breeding monogamous -- this is because over 90% of mouse housing for research is done in cages of a standard size, which, according to the new rules, will only allow 1 male and 1 female mouse to breed, instead of at least 2 females in a harem as would occur in nature. This hideous recommendation will double the cost of mouse housing, and will slow research, but worst of all, animal welfare will not be served by depriving mice of their natural breeding behavior. Get rid of this new recommendation, which has no basis in facts, and in which no one, especially not the mice, will be better off.


11 03/02/2011 at 01:03:03 PM Organization National Jewisih Health Denver, CO Comment 1:
I feel that the change in housing requirements for mice, specifically requiring the removal of either the male, one of the females, or the dam and her litter after delivery from the cage once a liter is dropped in a cage of triplets. This will serve to increase greatly the costs of breeding. Further, there is no firm scientific evidence that this is beneficial nor is there consensus amongst experts in this area. I strongly recommend that this not be adopted for use in the Guide.


12 03/02/2011 at 01:08:10 PM Self     Comment 1:
On the proposed use of pharmaceutical grade chemicals: this would seem to limit use of compounds that are made and supplied by various NIH institutes (e.g., NIDA, NIMH). This is a valuable Institute service to research that provides unusual, expensive compounds in amounts that adequate to animal studies. In addition, some items that should be considered (e.g., pharmacokinetics) when these compounds are used can only be known after they are given to animals.


Comment 2:
The prescribed once/week weighing frequency for food-restricted animals is not suitable and may be unnecessary, even risky in some situations. For example, non-human primates (and other larger species) often must be anesthetized (with attendant risks) for weighing. Experience shows that frequent weighing is useful to the point that stable feeding/weight conditions are established. After that point, the frequency of weighing can be decreased

13 03/03/2011 at 05:49:44 AM Self     Comment 1:
I encourage the use of the revised Guide by NIH. The profession needs direction as it relates to the use of laboratory animals. NIH has no other comprehensive and current resource to provide it's grantees with such guidelines. Though some might believe the revised Guide is not perfect - any subsequent effort by NIH will have similar detractors and will cost the Institutes time and money to produce.


14 03/03/2011 at 10:50:48 AM Self   Denver, Colorado Comment 1:
There is an important issue with the proposed 8th Edition of the Guide for the Care and Use of Laboratory Animals on which OLAW seeks comment. On page 57 of "The Guide", Table 3.2 lists recommended minimum cage floor space per mouse. The only change from the 7th edition is that breeding triads are not allowed in standard shoebox (77sq. inches) cages because it is recommended that a single female with a litter should have at least 51 sq. inches of space. The maximum recommended number of adult (>25 g) mice per shoebox cage remains at 5. However, there is no scientific basis for these recommendations. In fact, the references cited by authors of "The Guide" on p. 58 argue, if anything, that for many strains, more mice can be housed per cage than the minimum currently recommended by the 7th edition. I enclosed some of these citations for your perusal. One of these shows that C57BL/6 mice, housed at 10 per shoebox cage, are as healthy as those housed at 5 per cage. Another reference provides evidence of anxiety disorder in mice that are not sufficiently crowed. Therefore, on the basis of the science cited by the authors of "The Guide", I believe that breeding triplets (one male and 2 females) should be allowed, and that the minimum floor space per mouse should be halved relative to that currently recommended by the 7th edition, with the usual footnote that more space may be required for some strains or in special circumstances.

The cost of keeping a mouse colony has already reached an appalling level. I have a relatively small lab (6 people in total), and my research is based on genetically engineered mice. I routinely pay $5,000 to $7,000 a month for the mice. This is quite an absurd amount if you compare it to the average salary in the US. Implementing the space restriction recommended by the 8th Edition of the Guide would further increase the cost for mouse husbandry. The current NIH pay line for grant applications, in addition, is already significantly reducing the funds available to investigators with the risk that the scientific community is soon going to lose many genetically engineered mouse strains.

I consider myself a very sensitive person regarding animal welfare issues. However, I really do not see any justification in the space limit recommendations of the 8th or even the 7th edition of the Guide.

Thus, I recommend OLAW and AAALAC, and the scientific community not to implement the 8th Edition of the Guide.


15 03/03/2011 at 01:09:54 PM Self     Comment 1:
While I find the majority of the new Guide an excellent resource I have concerns over the change in cage height requirements for rabbits. The increase in height from 14 to 16 inches seems arbitary. The additional two inches places an undue burden on facilities to replace existing caging systems which are typically less than 16 inches high and does not enahnce animal well being.


16 03/03/2011 at 03:32:04 PM Self     Comment 1:
The current literature (published since the 1996 revision of the Guide) suggests that mice should actually be housed at higher densities in standard "shoebox" cages than recommended in the 1996 revision of the Guide for increased immune function, decreased mortality, and decreased fighting (Fullwood 1998, Gonder 2007, McGlone 2001, Smith 2004). If modern science suggests that higher housing densities are necessary for the health and welfare of mice, why would the Guide recommend lower housing densities?

The space constraints set forth in the new edition of the Guide appear to be specifically intended to disallow trio mating in a standard "shoebox" cage (http://books.nap.edu/openbook.php?record_id=12910&page=57) -- 67 sq in. (floor space of standard cage) - 51 sq in (space requirement for dam plus litter) - 15 sq in (space requirement for sire) = 1 sq in remaining. According to the Jackson Laboratory's Breeding Strategies for Maintaining Colonies of Laboratory Mice in the "Simple Breeding Schemes" section, "Most strains produce more progeny per cage if mated as trios because all adult cage mates generally help care for the young" (http://www.scribd.com/doc/48964381/breeding-strategies-manual). If the intention is to end trio mating, what institution has the expertise in mouse husbandry to outright discount Jackson Laboratory's 82 years of research in the field?

Given these issues of revised housing recommendations without scientific backing, the NIH must not adopt the eight edition of the Guide for the Care and Use of Laboratory Animals as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals.

Fullwood S, Hicks TA, Brown JC, Norman RL, McClone JJ. 1998. Floor space needs for laboratory mice: C57BL/6 males in solid-bottom cages with bedding. ILAR J 39:29-36.

Gonder JC, Laber K. 2007. A renewed look at laboratory rodent housing and management. ILAR J 48:29-36.

Institute of Laboratory Animal Resources. 1996. Guide for the care and use of laboratory animals. National Academy Press, Washington, D.C.

Institute of Laboratory Animal Resources. 2011. Guide for the care and use of laboratory animals. National Academy Press, Washington, D.C.

Jackson Laboratory. 2009. Breeding strategies for maintaining colonies of laboratory mice.

McGlone JJ, Anderson DL, Norman RL. 2001. Floor space needs for laboratory mice: BALB/cJ males or females in solid-bottom cages with bedding. Contemp Top Lab Anim Sci 40:21-25

Smith AL, Mabus SL, Stockwell JD, Muir C. 2004. Effects of housing density and cage floor space on C57BL/6J mice. Comp Med 54:656-663.


Comment 2:
The current literature (published since the 1996 revision of the Guide) suggests that mice should actually be housed at higher densities in standard "shoebox" cages than recommended in the 1996 revision of the Guide for increased immune function, decreased mortality, and decreased fighting (Fullwood 1998, Gonder 2007, McGlone 2001, Smith 2004). If modern science suggests that higher housing densities are necessary for the health and welfare of mice, why would the Guide recommend lower housing densities?

The space constraints set forth in the new edition of the Guide appear to be specifically intended to disallow trio mating in a standard "shoebox" cage (http://books.nap.edu/openbook.php?record_id=12910&page=57) -- 67 sq in. (floor space of standard cage) - 51 sq in (space requirement for dam plus litter) - 15 sq in (space requirement for sire) = 1 sq in remaining. According to the Jackson Laboratory's Breeding Strategies for Maintaining Colonies of Laboratory Mice in the "Simple Breeding Schemes" section, "Most strains produce more progeny per cage if mated as trios because all adult cage mates generally help care for the young" (http://www.scribd.com/doc/48964381/breeding-strategies-manual). If the intention is to end trio mating, what institution has the expertise in mouse husbandry to outright discount Jackson Laboratory's 82 years of research in the field?

Given these issues of revised housing recommendations without scientific backing, the NIH must not adopt the eight edition of the Guide for the Care and Use of Laboratory Animals as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals.

Fullwood S, Hicks TA, Brown JC, Norman RL, McClone JJ. 1998. Floor space needs for laboratory mice: C57BL/6 males in solid-bottom cages with bedding. ILAR J 39:29-36.

Gonder JC, Laber K. 2007. A renewed look at laboratory rodent housing and management. ILAR J 48:29-36.

Institute of Laboratory Animal Resources. 1996. Guide for the care and use of laboratory animals. National Academy Press, Washington, D.C.

Institute of Laboratory Animal Resources. 2011. Guide for the care and use of laboratory animals. National Academy Press, Washington, D.C.

Jackson Laboratory. 2009. Breeding strategies for maintaining colonies of laboratory mice.

McGlone JJ, Anderson DL, Norman RL. 2001. Floor space needs for laboratory mice: BALB/cJ males or females in solid-bottom cages with bedding. Contemp Top Lab Anim Sci 40:21-25

Smith AL, Mabus SL, Stockwell JD, Muir C. 2004. Effects of housing density and cage floor space on C57BL/6J mice. Comp Med 54:656-663.

17 03/04/2011 at 02:36:30 PM Self Indiana University Indianapolis, IN Comment 1:
As an investigator and as an IACUC member, I find the eighth edition of the Guide to be particularly unhelpful. I never thought that the earlier version was very helpful either. The Guide is full of generalizations that do not clarify questions of how an investigator should proceed or how an IACUC should judge the adequacy of a study protocol. For instance, in the section on Protocol Review (pp 25-26), a bullet point states: "appropriate sedation, analgesia, and anesthesia. (Indices of pain or invasiveness might aid in the preparation and review of protocols; see Appendix A, Anesthesia, Pain and Surgery)". However, there are no indices presented and there is no indication which of the many references in Appendix A might lead the investigator/IACUC member to such indices. This is akin to a travel guide saying: "Munich is a great town for eating schnitzel and drinking beer and there are numerous inexpensive zimmer freis where one can stay – to find these bed & breakfast places you should purchase the following 5 travel guide books and search through them thoroughly." Not very helpful – hardly what a guidebook is written to do. Sure, the section on Pain and Distress in Chapter 4 (pp 120-121) mentions some useful indicators of pain but it is not done in a way that is very helpful to an investigator when devising a set of specific criteria in a specific protocol. I think the authors of the Guide should have chosen a useful set of indices drawn from numerous sources and presented them in a usable fashion in a species-specific manner. The Guide is full of examples of vague guidelines that leave much room for interpretation and can only lead to confusion and frustration. In addition, there are examples where statements in the Guide serve to confuse the issue. For example, in the section on Program Oversight (p 25), the Guide states: "Program review and facilities inspections should occur at least annually or more often as required (e.g., Animal Welfare Act and PHS Policy)." Since the AWA clearly states that inspections should occur every 6 months, this statement is confusing and leaves the audience with questions rather than answers.

The paragraph above is just a sample of the tenor my review of the new edition of the Guide would have were I asked to do so for a reporting agency or a journal. I would conclude my review by saying: The new edition of the Guide, like its predecessor, falls flat as a guidebook. It lacks specific recommendations for investigators and IACUC members, relying instead on general statements that can be left to interpretation. In some cases, it makes statements that are inappropriate with regard to the regulations in question. This so-called guide is a recommendation for a blind-folded walk through the maze of regulations imposed by PHS and USDA.

As an IACUC member and as an investigator I have found it much more productive to refer to the Institutional Animal Care and Use Committee Guidebook published by ARENA and OLAW (the Guidebook). This text offers clear descriptions of the federal regulations, compares requirements of PHS and USDA, and gives clear examples of how to proceed on specific questions that often arise. My best recommendation is to scrap the use of the Guide as the basis for designing an animal use program and instead refer to the Guidebook.


Comment 2:
Stop the implementation plan.

Do not use the Guide as the basis for evaluation. The Guide presents cogent arguments for setting ethical standards for the use of animals in research, but it does little to guide the individual in specific steps needed in devising schemes that meet the regulatory standards set by the Federal agencies. The regulations set forth by the AWA, as interpreted by OLAW and ARENA in the Institutional Animal Care and Use Committee Guidebook published by ARENA and OLAW (the Guidebook), require specific actions. The Guide most often offers generalizations that may be left to interpretation that can lead to non-compliance. Instead, refer individuals and animal use program directors to the Guidebook as the basis for program/protocol design.

18 03/08/2011 at 01:25:55 PM Self     Comment 1:
I am familar with the contents of the 8th edition of the Guide for the Care and Use of Laboratory Animals. I enthusiastically support the adoption of this edition of the Guide as the basis for evaluation of institutional programs receiving Public Health Service support for activities involving animals. I believe that it is critical for the National Institutes of Health to have such guidelines on the use and care of live vertebrate animals in research, teaching and testing activities that are supported by federal dollars obtained from taxpayers.


Comment 2:
I support the proposed implementation plan.

19 03/08/2011 at 02:13:27 PM Self     Comment 1:
Written by experts who embrace humane and responsible animal research and the importance of performance standards, OLAW should adopt 8th Edition of the Guide.


20 03/08/2011 at 02:14:57 PM Self     Comment 1:
The new edition of the Guide appears to consider the AWA and Policies for the Humane Use of Animals in Research. The consistency provided in this revision is a significant improvement and should be implemented in reviewing support for PHS funded animal activities.


21 03/08/2011 at 05:22:47 PM Self     Comment 1:
The stipulation that pharmaceutical grade drugs should be used in all animal procedures unless there is no alternative would severely hamper research on drugs of abuse. The majority of the drugs we research that are relevant to drug abuse and addiction are available as pharmaceutical grade, but are prohibitively expensive as such. Studies requiring repeated treatment such as those utilizing self-administration, drug discrimination, or other procedures that allow assessment of tolerance or dependence would not be feasible under typical NIH grant budgets. Presently, NIDA provides many of these drugs at no cost to researchers, however they are not pharmaceutical grade as they are typically obtained from seizures of street drugs by law enforcement. Street drugs are rarely pharmaceutical grade. I am not aware of any data suggesting that the use of non-pharmaceutical grade drugs in addiction research has led to any complications or other problems solely because they were no pharmaceutical grade.

I sincerely hope that this requirement will be reconsidered.


22 03/09/2011 at 03:47:16 PM Self North Dakota State University Fargo, ND Comment 1:
The revised guide is an apprpriate standard for the use and care of laboratory animals in research. I suppport its adoption.


Comment 2:
At least one semiannual program and facility evaluation using the eighth edition of the Guide as the basis for evaluation is appropriate. I support implementation of such an in inspection.

23 03/09/2011 at 04:09:39 PM Organization National Association for Biomedical Research Washington, DC Comment 1:
March 9, 2011

Francis S. Collins, MD, PhD Director, National Institutes of Health Building One, 126 Shannon 1 Center Drive Bethesda, MD 20892

RE: Request for Extension to Comment Period for Proposed Adoption and Implementation of the Guide for the Care and Use of Laboratory Animals: Eighth Edition

Sent via electronic and U.S. Mail

Dear Dr. Collins:

On behalf of its more than 300 member institutions, many of which are affected Public Health Service (PHS)-assured institutions, the National Association for Biomedical Research (NABR) respectfully requests at least a thirty-day extension to the comment period provided by the NIH Notice, Laboratory Animal Welfare: Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals, published on February 24, 2011 (76 Federal Register 10379-80).

In order for institutions to adequately assess the substantive changes and additions to the Guide for the Care and Use of Laboratory Animals (Guide) and provide meaningful feedback regarding its impact on their animal care and use programs as requested, additional time is needed. The current timeframe set forth in the Notice is insufficient to accurately evaluate the consequences of NIH's potential adoption and implementation of the Eighth Edition of the Guide as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals.

Furthermore, Executive Order 13563, issued January 18, 2011 (76 Federal Register 3821-23), states that in order to promote participation each agency "shall afford the public a meaningful opportunity to comment through the Internet on any proposed regulation, with a comment period that should generally be at least 60 days." We believe that limiting the public comment period to thirty days is not in keeping with the spirit of OMB's stated intentions to allow for meaningful public input. Therefore, NABR requests that the comment period for the subject Notice be extended at least until April 24, 2011, which would provide a more commonly accepted 60-day comment period.

I hope that the NIH will agree to our request to extend the deadline for comments. Thank you for your consideration and please contact me if you have any questions.

Sincerely, Frankie L. Trull President National Association for Biomedical Research


24 03/09/2011 at 04:27:03 PM Self     Comment 1:
I support adoption of the eighth edition of the "Guide" as currently written. I believe it lays out reasonable guidelines for the use of animals and protects against unjustifiable use of animals.


Comment 2:
I support the proposed implementation plan as being reasonable and sufficient to ensure proper protection of animals.

25 03/09/2011 at 04:46:09 PM Self     Comment 1:
I strongly support the adoption of the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals.


Comment 2:
I also support the proposed implementation plan which would require that institutions complete at least one semiannual program and facility evaluation using the eighth edition of the Guide as the basis for evaluation by March 31, 2012.

26 03/09/2011 at 04:51:39 PM Self     Comment 1:
Yes. It is an important document for basic biomedical research.


Comment 2:
Yes, this seems appropiate.

27 03/09/2011 at 07:06:38 PM Self     Comment 1:
Adoption of the 8th addition of the guide will continue to ensure that animals used in research get the best possible care and provide the best possible model for studies important in understanding human disease processes and potential cures.


Comment 2:
Indeed the sooner a review is completed with the new guide, the sooner appropriate modifcations to individual programs can be made to remove any detrimental conditions or procedures.

28 03/09/2011 at 09:30:54 PM Self     Comment 1:
I strongly support the guidelines proposed in the eighth edition of the Guide for care and use of laboratory animals.


29 03/10/2011 at 12:37:32 PM Organization Council on Governmental Relations Washington DC Comment 1:
We are requesting an extension of the deadline for submission of comments in response to the National Institutes of Health request concerning the Proposed Adoption and Implementation of the Guide for the Care and Use of Laboratory Animals: Eighth Edition. We request an additional 30 days setting the deadline for comments on April 25, 2011.

The Council on Governmental Relations (COGR) is an association of 184 research universities and affiliated academic medical centers and research institutes. Our members and the research community generally need more than 30 days to assess the impact of the implementation of the Eighth Edition on the operation of facilities and the conduct of research using animals. The Eighth Edition introduces new standards in a number of areas including aquatic species and sets new standards for the environment, housing and physical plant including new minimum cage requirements for rodents and rabbits. The research community needs sufficient time to assess these standards and their related costs to offer thoughtful and thorough comments to NIH. Additional time will not compromise the care and use of animals used in PHS-supported research because we remain responsible for compliance with the earlier 1996 version of the Guide. The Health Research Extension Act of 1985 requires notice and comment on the policy and we appreciate the opportunity. In the spirit of the call for a "meaningful opportunity to comment" on new regulations articulated in EO 13563, we request an extension of the deadline.


Comment 2:
See above

30 03/10/2011 at 01:09:31 PM Self     Comment 1:
I whole heartedly endorse the long-awaited 8th edition of the Guide for the Care and Use of Laboratory Animals.


31 03/10/2011 at 05:46:00 PM Self     Comment 1:
I like the new updates, making it more current and clarifying some ambiguities.


32 03/10/2011 at 06:07:34 PM Self Oregon health and science university   Comment 1:
I support adoption


33 03/11/2011 at 11:45:39 AM Organization Association of American Universities and Association of Public and Land-grant Universities Washington, DC Comment 1:
March 11, 2011

Patricia Brown, VMD, MS NIH Office of Laboratory Animal Welfare Office of Extramural Research RKL1, Suite 360 6705 Rockledge Drive Bethesda, MD 20892-7982

Dear Dr. Brown:

On behalf of the Association for American Universities (AAU) and the Association of Public and Land-grant Universities (APLU), please accept this request for an extension of the deadline for submission of comments in response to the National Institutes of Health notice (FR Doc. 2011–4172) concerning the Proposed Adoption and Implementation of the Guide for the Care and Use of Laboratory Animals: Eighth Edition ("The Guide"). We request an additional 30 days with a suggested new comment deadline of April 25, 2011.

AAU and APLU's combined memberships include most of the major public and private research universities in the United States. We greatly appreciate the opportunity to comment on whether NIH should adopt The Guide, as well as on the proposed implementation plan, and applaud NIH for exploring the potential impact of this policy change. However, in order to provide "insight from institutions on the impact of changes to the Guide on their animal care and use programs" as requested, our members and the research community need more than 30 days. As noted in the Federal Register notice, the Eighth Edition "contains substantive changes and additions from the previous additions." The research community needs sufficient time to assess the consequences of these changes and their related costs in order to offer thoughtful and thorough comments to NIH. Additional time will not compromise the care and use of animals used in PHS-supported research because we remain responsible for compliance with the earlier 1996 version of the Guide.

Therefore, we respectfully request that you extend the comment period to April 25, 2011. Thank you for consideration of this request. Sincerely,

Respectfully,

Robert M. Berdahl President Association of American Universities

Peter McPherson President Association of Public and Land-grant Universities


34 03/11/2011 at 04:10:33 PM Self Oregon Health and Science University Portland, OR Comment 1:
I support the proposed adoption of the Guide for the Care and Use of Laboratory Animals: Eighth Edition (Guide)


Comment 2:
I support the proposed implementation of the Guide for the Care and Use of Laboratory Animals: Eighth Edition (Guide)

35 03/11/2011 at 04:58:18 PM Self     Comment 1:
The guide for the Care and Use of Laboratory Animals Eighth Edition should be adopted as a basis for evaluation of institutional programs across the United States.


36 03/11/2011 at 08:02:08 PM Self     Comment 1:
YES,adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals.


Comment 2:
YES, require that institutions complete at least one semiannual program and facility evaluation using the eighth edition of the Guide as the basis for evaluation by March 31, 2012.

37 03/13/2011 at 12:04:58 PM Self     Comment 1:
I have been involved in the care and use of laboratory animals since 1982 = 28 years. My comments with regard to the above question is: NO, the 8th edition of the Guide for the Care and Use of Laboratory Animals should NOT be adopted by OLAW. It was not properly reviewed according to standard Federal government procedures, so we do not know if all aspects of it are even legally defensible. Apparently no one bothered to even try to calculate the costs to the regulated entities of the mandated changes to animal cages (rabbit cages at least) is disingenuous and deceitful. The fact that the Director of NIH had to be the one to insist that proper procedures be followed (after he became aware of the added costs of adopting the 8th edition to just the intramural program - not to mention all the grant recipients) shows how flawed the whole process has been. In the current economy of universal budget cuts, now is NOT the time to require institutions to spend even MORE money to comply with new regulations. Stay with the 7th edition until the 8th edition can be made acceptable to the regulated entities and then only after following all standard Federal review processes, including a public comment period that is not limited to two questions and nothing else, should the 8th edition ever see the light of day again. Do NOT adopt the 8th edition until it can be done correctly, and do NOT adopt it when it increases financial burden on the regulated entities at a time of severe fiscal crisis. Miserable timing.


Comment 2:
This question assumes that the first question will be answered in the affirmative. This is very poor survey construction. My comment: NO = There should be NO implementation plan until the 8th edition can be re-written to be less burdensome and then properly routed for reviewed according to standard Federal government procedures.

Go back to the drawing board, make the 8th edition LESS burdensome rather than MORE burdensome, and then go through the proper procedures to get it accepted by all before even considering adopting it.

Do it right or don't do it at all!

38 03/13/2011 at 07:43:46 PM Self California Institute of Technology Pasadena, CA 91105 Comment 1:
It is a disappointment that a more thorough revision of the guide was not accomplished, with a eye to reducing paperwork and expense for investigators. Since the research is supported by the public through government agencies and done to benefit the public, reducing the cost of unnecessary compliance would be a win-win situation.


Comment 2:
Already, some of the requirements for cleanliness and safety, as well as the semiannual program and evaluations, especially for rodent facilities, exceed those for similar facilities used to house or operate on humans. Daily census for rodents far exceeds the human census done only every 10 years.

39 03/14/2011 at 08:44:30 AM Self     Comment 1:
Please adopt the new Guide. It is a necessary step forward.


Comment 2:
Please adopt the new Guide. It is a necessary step forward.

40 03/15/2011 at 03:23:27 PM Self University of Maryland Baltimore, Maryland Comment 1:
I request that you DO NOT implement the recently prepared 8th Edition of the "Guide for the Care and Use of Laboratory Animals".

In my opinion as a relatively senior biomedical researcher, there are no important deficiencies in the currently used 7th Edition of the Guide. Its continued use fully supports and prioritizes animal welfare, is based upon "best practices", and thus facilitates humane, high-quality biomedical research. The proposed changes to the Guide in the 8th Edition are not supported by any credible scientific data. They are very unlikely to improve the scientific quality of the research, or improve animal welfare. As such the very expensive and complicated proposed changes would impose a large and wholely unjustifiable fiscal and logistical burden on the national research enterprise, with no expected "return on investment". Well intentioned, but VERY BAD POLICY.


Comment 2:
It is wholely unrealistic to expect the entire research enterprise of the United States to re-tool completely in one year!

41 03/15/2011 at 04:15:05 PM Self     Comment 1:
Current 7th edition is adequate for animal welfare and animal research data quality. Precious dollars should be spent on research during this time of budget crisis, so I don't support adoption of 8th edition


42 03/15/2011 at 04:23:35 PM Self Univ. of Maryland, Baltimore Baltimore, MD Comment 1:
As a University of Maryland, School of Medicine researcher who uses mice and other rodents, I would suggest that implementation of the new 8th Edition of the "Guide for Care and Use of Laboratory Animals" be delayed until our country gets its fiscal act together. My NIH grants have been cut significantly across the board, and implementation of the practices proposed in the 8th Edition will be passed along to the investigators. Implementation of the 8th Edition is something that can be put on the back burner until funding has stabilized and scientists can absorb the additional costs of animal care.

Thank you.


43 03/17/2011 at 10:50:07 AM Self     Comment 1:
I strongly support adoption of the eighth edition of the guide. The Guide has long provided a reasonable set of standards by which ethical research studies using animal models can be performed. Animal models are absolutely crucial to medical and basic research progress.

*****


Comment 2:
Two areas of the proposed implementation plan require further modification, in my opinion. Both are on pp 30-32 of the draft guide.

First, the proposed language would require purchase of "pharmaceutical grade" chemicals for all studies with animals. The intent here is laudable - none of us who work with animals wants to administer poor quality compounds that might contain contaminants that might have undesirable side effects. However, the realities of research has taught us that chemicals that are purified to "pharmaceutical grade" are nearly always much more expensive than simply "analytical grade" or other non-pharmaceutical grade products. The further reality is, for many compounds, there is absolutely no safety risk to the animal. The requirement as currently proposed is backwards. It should be acceptable to use compounds of any reasonable purity unless there is reason to believe, for that specific compound, that to do so might be unsafe for the animals. The result of adopting a "pharmaceutical-grade" requirement will, quite simply, be that for nearly all compounds I will seek exemption to use a lesser quality in my protocols, and will waste a lot of my time and my IACUC's time.

The other issue that should be discussed further is the apparent proposal that use of preferred foods as reinforcers should be preferable to the use of very mild food restriction in behavioral protocols. There is a very extensive published literature in the animal learning area that demonstrates quite clearly that these two sources of motivation are not behaviorally equivalent for animals. Mild food deprivation protocols that have no detrimental physiological consequences for the animals are well-understood. There is a large literature that even much more significant food restriction on a permanent basis has health benefits. So, making a default requirement that preferred foods should be used is unreasonable scientifically and will not protect or improve animal health.

*****

44 03/17/2011 at 04:26:46 PM Self     Comment 1:
The Guide should be adopted, but requires revision. It should not be adopted or used in earnest until the revision issue has been put to rest.


Comment 2:
It is certainly possible to put institutions through a semi-annual under the new "Guide" by March 2012, but there is not sufficient time to ensure compliance particularly in the way of rabbit socialized housing, the essential outlawing of trio mouse mating (and its ramifications for more caging and expanded animal facilities), the intensive training of personnel involved in surgery, and the relocation of rodent surgery procedures from laboratories to dedicated procedure space.

45 03/18/2011 at 12:38:20 PM Organization National Biodefense Analysis and Countermeasures Center Frederick, MD Comment 1:
We fully support the adoption of the 8th edition of the Guide for the Care and Use of Laboratory Animals (Guide) by the National Institutes of Health (NIH) and the proposed implementation plan. While the vast majority of the changes to the 8th edition of the Guide provide much needed improvements and clarifications on the standards for research animal care and use programs and facilities, there are a small number of issues that could be misinterpreted by either oversight agencies or research facilities using the Guide as a standard. While most comments apply directly to NIH funded research, a few comments do not but still could result in significant confusion across biomedical research facilities in the United States. These issues are provided as follows:

Page 25 Topic: Frequency of Program Review and Facilities Inspections The new Guide states "Program review and facilities inspections should occur at least annually or more often as required (e.g., by the Animal Welfare Act and PHS Policy)." While the Animal Welfare Act and PHS Policy both require semiannual program review and facility inspection, not all research entities, even in the United States, are subject to these regulatory requirements. This will lead to a disparity in requirements for those research entities who utilize the Guide as a guidance document but not the other documents cited. The IACUC is a mechanism of self-regulation and conducting annual reviews of the animal care and use program and facilities is not of a sufficient frequency to identify and resolve program and facility issues in a timely manner.

Page 26 Topic: Protocol Review A new requirement for protocol review states that the protocol should include a "method of euthanasia or disposition of animals, including planning for care of long-lived species after study completion." The latter part of this statement is very ambiguous and should be clearly defined as to what constitutes "care" and what are considered "long-lived species." This could easily be interpreted by oversight agencies as the need to establish retirement funds designed to maintain animals in sanctuaries for the remainder of their natural life. While this is currently done for chimpanzees, this would result in a phenomenal increase in the cost for research if the intent of this guidance was to include more commonly used nonhuman primates such as Old World macaques.

Page 26 Topic: Protocol Review While the new Guide advises that the responsibility for scientific merit review normally lies outside the IACUC, it states "in the absence of evidence of a formal scientific merit review, the IACUC may consider conducting or requesting such a review (Mann and Prentice 2004)." This statement has considerable implications for programs not utilizing the NIH grant review system and leaves the question of "formal review" open to interpretation by oversight agencies. Clarification should be provided as to whether a formal scientific merit review can be performed internally or if the expectation is that it be performed by an external, independent group of scientists.

Pages 59 and 61 Topic: Minimum Space Tables 3.3 and 3.5 The title of the tables prescribing minimum space requirements for rabbits, cats, and dogs (Table 3.3) and nonhuman primates (Table 3.5) changed from "minimum space requirements for individual animals" in the old Guide to "individual space requirements for animals housed in pairs or groups" in the new Guide. While there are some differences in floor space and height requirements, the space requirements are similar in both versions of the Guide. The change with the greatest impact involves the addition of the statement to both tables that states "singly housed animals may require more space per animal than recommended for pair- or group-housed animals." Caging manufacturers have produced cages with dimensions based on the minimum space required for individually housed animals as specified in the 7th edition of the Guide. An implication, and possible expectation, that individually housed animals should now have more space will cause confusion not only to the cage manufacturers on how large to make cages for these species, but could result in all the existing cages in use for these species to now be unusable when housing animals individually, which is often needed due to veterinary care or experimental requirements (e.g., quarantine, infectious disease research). Depending on how this new requirement is interpreted by regulatory agencies, this could have a huge economic impact if new caging must now be procured whenever the single housing of animals is required. Without solid scientific evidence that single housed animals benefit from having larger amounts of space over the stated individual space requirement for group housed animals, this requirement will result in the unnecessary diversion of funds from science and confusion among animal care and use programs.

Page 139 Topic: Heating, Ventilation, and Air Conditioning (HVAC) With regard to animal room humidification, the new Guide states "Ideally relative humidity should be maintained within ±10% of set point; however, this may not be achievable under some circumstances." While the Guide recognizes that this may not be achievable, the sentence sets a standard that is unachievable by most all older facilities and many new ones. Even with the caveat, the stated preference of no more than a 10% variation of humidity levels from set point will be used by regulators and oversight agencies as an engineering standard. It should be made clear by regulatory and oversight agencies that this is an unrealistic goal and that as long as humidification levels remain between Guide recommended parameters (i.e., 30-70%), and there are no adverse health effects, that the 10% variation requirement will not be used as a standard when evaluating animal facilities.


Comment 2:
The implementation plan is reasonable and provides sufficient time for programs to incorporate changes to the Guide.

46 03/19/2011 at 12:15:03 PM Self     Comment 1:
i do not believe these standards for lab care of animals are humane at all. you can see the video of the way lab animals are actually kept. those pictures are all over the web on youtube of the abuse to lab animals. i want higher standards. i do not want th eindustry to set standards because they will always want to continue abusing animals. i want humane animal protectors to be brought in to upgrade the standards. the standards are lax and abusive. i think the time to comment should be extended. i would like to have a paper copy sent to me to comment in more detail because i have no access to the lab standards in some obscure book.


Comment 2:
all use of lab animals should be stopped immediately. i think mice and rats are the only animals i would allow to be used in experiments. no other animal should ever be used. the fact is that there are other testing methods that are more accurate, cheaper and more relevant to people than this stupid use of animals which dates from l500 a.d. it is amazing that just becuase profiteers make money from this disgusting industry that scientific minds continue to allow it to continue. that shows a real problem with scientific minds these days. they have no common sense at all.

47 03/22/2011 at 02:50:50 PM Self     Comment 1:
I have read the "Guide for the Care and Use of Laboratory Animals" and would like to see the eighth edition adopted. As I am strongly opposed to the use of animals at all in research and testing, it is only decent that scientists do all they can to make lab animals feel as comfortable as possible, and eliminate as much stress and pain as possible. Animals are unwilling participants in research and testing, and don't deserve to suffer like they do. Whenever non-animal resources are available, it is incumbent upon scientists and researchers to use them instead of animals.


Comment 2:
I support institutions evaluating their compliance to the Guide, and would like to see an evaluation of the personnel's treatment of animals; plus animal conditions such as room temperature, water and food, comfort, room to move around; and safety issues, every 6 months. And wouldn't it be better to have an outside agent do the evaluation for an objective view of all of this?

48 03/25/2011 at 08:23:35 AM Self     Comment 1:
*REVISED* Comments on Laboratory Animal Welfare: Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals Submitted for the record by Roscoe G. Bartlett Member of Congress Sixth District of Maryland

I would like to highlight the concerns I have of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals. The University of Maryland, School of Medicine and a small business located in my district, Spring Valley Laboratories, have contacted me regarding the proposed new laboratory guidelines. Addressing the complete set of guidelines Louis DeTolla, V.M.D.,Ph.D.,DACLAM of the University of Maryland, School of Medicine states that, "There are no deficiencies in the currently used 7th Edition of the Guide, so its continued use fully supports animal welfare, best practices, and quality biomedical research. The proposed changes to the Guide in the 8th Edition are not supported by data that demonstrate any improvement in scientific outcome of animal studies or benefits in animal welfare as a result of these changes."

Specifically, I am concerned that the costs to academia and small businesses do not justify the negligible benefits to the laboratory animals regarding cage sizes. The additional size requirements (i.e. increasing the height requirement for rabbit cages from 14" to 16") will be very costly to labs and small businesses. For example, the cost to the University of Maryland would be $230,000 to replace existing caging. The impact to Spring Valley Laboratories will be more profound. The dollar cost could be as much as $400,000 but final result of these regulations could drive them out of business.

As you grapple with developing new guidelines, please consider the following: 1. The Regulatory Flexibility Act of 1980 (amended in 1996) requires that the rulemaking process include cost/benefit analysis of new regulation to small businesses. In this case, the cage size increases compared to the reductions in the amount of money available for advances in medical research and the cost of jobs; 2. The size of the animal in relation to the newly proposed cage size (for example all rabbits are not the same size); 3. A plan to grant exemptions to the Eight Edition guidelines for institutions and businesses with existing cages which meet the specifications of the Seventh Edition of the Guide for the Care and Use of Laboratory Animals.

***


Comment 2:
*REVISED* Comments on Laboratory Animal Welfare: Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals Submitted for the record by Roscoe G. Bartlett Member of Congress Sixth District of Maryland

I would like to highlight the concerns I have of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals. The University of Maryland, School of Medicine and a small business located in my district, Spring Valley Laboratories, have contacted me regarding the proposed new laboratory guidelines. Addressing the complete set of guidelines Louis DeTolla, V.M.D.,Ph.D.,DACLAM of the University of Maryland, School of Medicine states that, "There are no deficiencies in the currently used 7th Edition of the Guide, so its continued use fully supports animal welfare, best practices, and quality biomedical research. The proposed changes to the Guide in the 8th Edition are not supported by data that demonstrate any improvement in scientific outcome of animal studies or benefits in animal welfare as a result of these changes."

Specifically, I am concerned that the costs to academia and small businesses do not justify the negligible benefits to the laboratory animals regarding cage sizes. The additional size requirements (i.e. increasing the height requirement for rabbit cages from 14" to 16") will be very costly to labs and small businesses. For example, the cost to the University of Maryland would be $230,000 to replace existing caging. The impact to Spring Valley Laboratories will be more profound. The dollar cost could be as much as $400,000 but final result of these regulations could drive them out of business.

As you grapple with developing new guidelines, please consider the following: 1. The Regulatory Flexibility Act of 1980 (amended in 1996) requires that the rulemaking process include cost/benefit analysis of new regulation to small businesses. In this case, the cage size increases compared to the reductions in the amount of money available for advances in medical research and the cost of jobs; 2. The size of the animal in relation to the newly proposed cage size (for example all rabbits are not the same size); 3. A plan to grant exemptions to the Eight Edition guidelines for institutions and businesses with existing cages which meet the specifications of the Seventh Edition of the Guide for the Care and Use of Laboratory Animals.

***

49 03/25/2011 at 08:56:18 AM Organization University of Maryland Baltimore, MD Comment 1:
The current policies are working and adoption of these new policies will not make a big change. With budget cuts, rises is COLA adoption this policy would increase additional financial strain on the institutions, principal investigators and ultimately the ability to deliver good and usable scientific data. Thus I respectfully, request a postponement of the implementation of this new policy.


Comment 2:
Under normal conditions, implementation of this proposal would have been ideal. However, it is important to note that many research and organizations are under a continuous pressure of budget cuts imposed by the Federal, state and local governments. Many support personnel have been either laid off or working part time to cope up with these changes. The adoption of the proposed actions will result in additional price raises by the veterinary services at different universities. Ultimately, the PI of NIH funded grants or other types grants will not be able to deliver results with increased charges for animal welfare. The current laws sufficiently address many concerns. Thus, it is important the NIH not adopt this new policy and should not implement at this stage.

50 03/25/2011 at 02:28:56 PM Organization American Farm Bureau Federation Washington, DC Comment 1:
American Farm Bureau Federation 600 Maryland Avenue SW Suite 1000W Washington, DC 20024

March 25, 2010

Office of Laboratory Animal Welfare Office of Extramural Research National Institutes of Health RKL1, Suite 360 6705 Rockledge Drive, Bethesda, MD

Re: Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals

As the organization representing the largest number of American livestock, dairy and poultry producers, the American Farm Bureau Federation has a deeply vested interest in ensuring that science-based principles are available to guide the proper care and treatment of animals in agricultural production. We appreciate the opportunity to comment on the proposed adoption and implementation of the January 2011 eighth edition of the Institute for Laboratory Animal Research (ILAR) Guide for the Care and Use of Laboratory Animals (ILAR Guide) as a basis for evaluation of institutional programs receiving Public Health Service support involving animals. After reviewing the updated guide, it has come to our attention that the document has many technical flaws related to agricultural animal care.

Farm Bureau opposes the adoption by the National Institutes of Health (NIH) of the ILAR Guide as currently published. As we discussed with NIH representatives on Feb. 1, we agree with numerous scientific experts and animal science researchers that the ILAR Guide is flawed in its ethical position. Many of its elements are inconsistent with scientific recommendations for the care of farm animals.

Perhaps most important, strict use of the guide would negatively impact animal care. Scientists that work in the field of large animal welfare have pointed out specific deficiencies in the requirements listed in the ILAR Guide for these animals' needs.

Unscientific animal care guidelines pose a threat to animals as well as the producers and researchers responsible for their well-being. We are concerned that the adoption of inaccurate standards by NIH would harm agricultural animals in the care of the Public Health Service, and by precedent, animals in academic research and the private sector. This precedent is not only confusing but potentially dangerous, as it starts down the slippery slope of basing care standards on something other than science.

In January 2010, the Federation of Animal Science Societies (FASS) published an updated Guide for the Care and Use of Agricultural Animals in Teaching and Research (Ag Guide). This document was written by 64 professionals with expertise in farm animal care and contains a wealth of substantive technical information about the care of farm animals in teaching or research (agricultural or biomedical). Unlike the ILAR Guide, the Ag Guide contains appropriate, tested and practical protocols for such criteria as sanitation protocols, air temperatures and floor space, to name just a few. All recommendations in the Ag Guide are based upon peer-reviewed research.

The Ag Guide is the most scientifically valid, current resource document for agricultural animal care. We strongly urge NIH to adopt and recognize it as the sole reference for farm animal care.

Sincerely,

Mark Maslyn Executive Director Public Policy


51 03/28/2011 at 09:07:08 AM Organization MB Research Labs Spinnerstown, PA Comment 1:
The Eighth Edition of the Guide has changed the height requirement of rabbit primary enclosures from 14" to 16". Prior to NIH acceptance of the Guide for PHS support, this change should be questioned.

The 16" criteria may be suitable for very large rabbits but requiring the height for all animals seems questionable. The use of performance criteria based on animal weight or age should be considered. The economic impact of changing all caging will be significant. We presently inventory approximately 200 rabbit cages which conform to the 14" criteria. Replacing these cages will result in a large financial burden.

I suggest that NIH consider instituting performance standards based on animal weight.


52 03/29/2011 at 03:18:47 PM Self Oregon Health and Science University Portland, OR Comment 1:
The guide should be adopted.


Comment 2:
Current requirements are sufficient. No additional regulatory requirements should be imposed on institutions.

53 04/01/2011 at 02:58:44 PM Organization Oregon National Primate Research Center Beaverton, Oregon Comment 1:
We strongly support the adoption of the 8th edition of the Guide for the Care and Use of Laboratory Animals and appreciate the importance of housing animals in cages appropriate for their Psychological, social and Physical needs.

In the case of non-human primates we understand and appreciate the need for increased cage height to meet the conformational and behavioral needs of the animals. The recommended cage size for non-human primates in The Guide will make some caging obsolete and will require major engineering changes in animal housing buildings, rooms and cages. This will result in substantial cost without providing a mechanism for re-capturing those costs through granting programs since the G-20 process has been discontinued.

Because of these financial constraints, it may not be possible for us to perform a semiannual inspection using the new standards by the recommended date of March 25, 2012.


54 04/04/2011 at 12:14:42 PM Organization Thomas Jefferson University Philadelphia, PA Comment 1:
Expanding the required amount of cage space for housing experimental mice in breeding protocols would have several negative effects that should be considered. First, during these trying economic times not being able to use breeding trios will double an investigator's expense for breeding cages. Also, the use of trios ensures that if one female perishes there is another lactating female who can nurse the pups. This prevents young pups from starving to death. For certain strains it has been published previously that the males help the mother at times by laying on the pups to keep them warm. Also, the removal of a male when a mother has young pups can cause her to cannibalize her litter. If a males is "hopped" between two cages with two females, then one of the female cages will not receive assistance from the male when raising pups. Additionally, if the male is hopped at the wrong time this can result in more eaten litters.


55 04/05/2011 at 05:39:11 PM Self     Comment 1:
"The use of non-pharmaceutical-grade chemicals or substances should be described and justified in the animal use protocol and be approved by the IACUC" There are many instances when nonpharmaceutical grade compounds or substances may be appropriate and allowances should be made for IACUCs to establish policies governing their use that do not require prior IACUC approval. Specific examples include when a nonpharmaceutical grade compound or substance is used for nonpharmaceutical purposes such as the use of doxycycline to regulate gene expression or the use of sterile PBS as a diluent for research reagents. If efficacy of the compound is not an issue because the compound is not being used therapeutically (eg. antibiotics, anesthetics, etc.) and if proper precautions to ensure sterility, freedom from particulates, and safety of the compounds is a prerequisite, then the use of professional judgment in creating an appropriate policy should be permitted. Blanket statements such as "They should therefore be used, when available, for all animal-related procedures" do not provide the flexibility needed in a diverse research environment. Similarly, the term "animal-related procedures" is vague and open to extreme interpretations (is a necropsy an animal-related procedure? a bath?). All "live animal-related experimental procedures" would offer some better definition.


Comment 2:
"Single housing of social species should be the exception and justified based on experimental requirements or veterinary-related concerns about animal well-being." It would be very beneficial to readers if the Guide could indicate to which commonly used species this applies - provide examples.

56 04/07/2011 at 03:51:19 PM Self     Comment 1:
After reading the Eighth Edition of the Guide for the Care and Use of Laboratory Animals, we feel strongly that it should not be adopted as it is, but should be sent back for revision and clarification. While some necessary updates are included, several statements within the Guide are ambiguous and others are not appropriate for the use of species such as rodents and fish. We think that the lack of discussion of species-specific requirements for optimal care and management is a major problem with the Guide as written. If adopted in its present form, the Guide is likely to be interpreted variably by readers at different institutions and increase the regulatory burden on those who work with animals. Of great relevance, it appears that the committee that wrote the Guide included minimal representation from the scientific community who actually use animals in their research. We believe that having a balanced committee is key to having a clear and useful document and that this unbalanced committee structure may underlie the specific issues listed below. 1. Guide page 27-"Experimental and Humane endpoints". We believe that this distinction is false and will be interpreted to mean that some procedures in IACUC-approved documents are inhumane. Before any proposal is submitted by the investigator or approved by an IACUC, alternatives are considered fully. In approved protocols, IACUC-approved experimental and human endpoints are identical. During the course of studies, investigators continually re-evaluate the endpoint criteria necessary to meet the scientific goals and the necessity of any adverse affects that have been previously approved. This change in the Guide may directly hamper research efforts by raising questions about "inhumane" endpoints. 2. Guide page 25-"A clear and concise sequential description of the procedures involving the use of animals that is easily understood by all members of the committee." This addition to the Guide does not affect animal welfare, but increases the regulatory burden on investigators. Description of Study Objectives in lay terms is already required (and often difficult); any procedures that are not easily understood can be discussed at committee meeting. If necessary, investigators could be asked for additional clarification for those few cases in which procedures are not clear or adequately justified. 3. Guide page 64-"Social environment"-The concerns raised about social housing apply minimally to mice, rats or fish. Mice, rats and fish should be exempt from these social pairing requirements. The Guide should state that while mice and rats are social animals and single housing is discouraged, they are exempt from the need for provision of scientific justification and review of social housing requirements. Appropriate environmental enrichment for mice and rats is encouraged. 4. Guide pages 29 and 64-Restraint devices. It is unreasonable to broadly apply the information in the physical restraint section, which describes requirements for training and habituation, to laboratory mice, rats and fish. Training and habituation is generally not feasible due to the numbers of animals involved and average length of experiments. Training and habituation should not be required for the restraint of rodents for acute and transient procedures. Only prolonged restraint or restraint used as an experimental stressor for rodents should require description and justification. Listing the restraint methods to be used on the animal study proposal is appropriate in all cases. It should be clarified that animals that fail to adapt should be removed from the study when the failure poses a reasonable risk to the animal or personnel, or adversely affects the animal's health and welfare or study objectives. Finally, fish should be excluded from the physical restraint and training section. 5. Guide page 30-Food and fluid regulation. The requirement that written records of daily food and fluid intake be maintained for individual animals in experiments involving food or fluid restriction should be waived for mice, rats and fish. Measuring intake is virtually impossible for mice or rats unless they are singly housed, which is not recommended elsewhere in the Guide. The IACUC should decide when records are required, unless adverse effects are observed during daily monitoring. 5. Guide page 115-Surgery-"The IACUC, together with the AV, is responsible for determining that personnel performing surgical procedures are appropriately qualified and trained in the procedures (Anderson 2007)." The IACUC should be responsible for supervision. The AV should provide guidance but there will be a potentially adversarial relationship if the AV is also responsible for determining whether personnel are appropriately qualified. 6. Guide page 123-Euthanasia-"Standardized methods of euthanasia that are predictable and controllable should be developed and approved by the AV and IACUC."This is the same issue as in item #5. The IACUC should have the final authority in all areas of euthanasia. 7. Guide page 15: Interinstitutional Collaborations - . "In cases of such collaboration involving animal use (beyond animal transport), the participating institutions should have a formal written understanding…" This creates an unnecessary regulatory burden. OLAW should clarify that the Guide is concerned with animal care and services and not with typical scientific collaborations between investigators at institutions with PHS assurances.


57 04/12/2011 at 03:02:49 PM Self     Comment 1:
Table 302 on page 57 and the related discussion regarding space requirements for rodent housing are completely inadequate for use as an evaluating tool for rodent research programs for the following reason: The section manages to completely confuse the space requirements for harem breeding or even pair breeding, as there is only a size requirement for a single animal (the dam) with a litter. There is no obvious answer to the question- What is the space requirement for more than one adult with a litter? This is unacceptable, as pair breeding or harem breeding are the primary methods for breeding rodents. This section only creates confusion as to what the appropriate size cage would be for these situations. The size caging that you would end up with for these situations is unreasonable and would create an unreasonable and unsustainable cost for institutions conducting research as breeding programs would take up at least two times their current space, if not more. Their would also be costs associated with new caging required, protocol changes, training requirements exc. I believe the Guide would have to amend this table to correct the issue before it would be usable as an evaluation tool for institutions using rodents for research.


58 04/12/2011 at 06:06:27 PM Self     Comment 1:
Chapter 4, pp 114 ...investigator and veterinary staff cannot reach consensus on treatment, the veterinarian must have the authority, delegated by senior administration (see Chapter 2, Institutional Official and Attending Veterinarian) and the IACUC, to treat the animal, remove it from the experiment, institute appropriate measures to relieve severe pain or distress, or perform euthanasia if necessary.

This is in direct conflict with 21 CFR 58.33 The study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results, and represents the single point of study control.

In addition, 9 CFR 2.31 empowers the IACUC committee to resolve differences in opinion between SD and Veterinarian.

It would be a violation of the USDA regulations for the Veterinarian to act unilaterally and intervene against SD opinion, without IACUC consideration and approval. Endpoints and pain/morbidity level plans are a required part of the IACUC protocol approval process. If the Veterinarian is concerned about endpoints or pain management plans, the time to voice those concerns are prior to start of study. Interference can result in biased data and skew endpoints required for FDA decision making and ultimately endanger human health where such endpoints are ignored in favor of animal comfort. Critical data can be lost or obscured under the guise of protecting the test subject.

FDA regulations are designed to create studies which per 21 CFR 58.120 reduce bias and per 21 CFR 58.33 capture all data including unanticipated results which may point to future human safety issues thereby saving lives in future clinical trials.

The Veterinarian having the authority to act unilaterally without IACUC consideration and approval is unacceptable and violates FFDCA and the regulatory authority of the FDA.

Currently the Federal Register Vol 76 March 29, 2011 list April 24, 2011 as the final date for comment.

In addition to the problem with the Study Director – Vet conflict there are a number of revisions of cage dimensions which are virtually unavailable in the market making cage sizes obsolete and creating a rather unreasonable financial burden on all research organizations.


59 04/13/2011 at 08:21:18 AM Self     Comment 1:
The new Guide's "should" level recommendations for behavioral research are alarmingly naive, anthropomorphic, and have no basis in science. For example, the "shoulds" about diet restriction have no basis in science, and they ignore both the well documented health and well-being effects of moderate dietary restriction and the fact that there is no evidence that such regimens produce anything approximating chronic distress.


Comment 2:
The recommendations about the use of pharmaceutical grade drugs for pharmacology research are not simply cumbersome, they promote bad science. Also of note is the complete absence of any evidence whatsoever that health and welfare of animals have been compromised by the use of research grade drugs (i.e., pure and in a known vehicle that is usually without effects of its own).

60 04/13/2011 at 04:51:59 PM Self     Comment 1:
I support the use of the 8th edition of the Guide for Animal Care and Use. In general, the revisions in the latest edition are needed and remedy several deficiencies in the previous edition.


Comment 2:
I believe that the implementation time needs to be extended at least one year. It will be very difficult for institutions to make the changes necessary to be in compliance with the new quidelines by March 31, 2012.

61 04/14/2011 at 03:24:55 PM Organization Drexel University College of Medicine Philadelphia, PA Comment 1:
The eighth edition of the Guide should NOT replace the 1996 edition. The sheer burden of many of the proposed modifications do nothing to increase the care, use and welfare of laboratory animasls and add substantial expenses to both the institution and to the individual investigator. In a time of severely diminishing budgets for research, in a time of substantial cuts to academic institutions, these proposed changes will only further diminish our competitive stance in the healthcare community, will impact on the discovery of new drugs and will further debilitate our younger scientists - all without any derived benefit to the laboratory animals that are so vital - and so adequately cared for under the present guidelines - to our research enterprise.

Finally, I wish to comment on the proposed modification on the use of "nonpharmaceutical grade" drugs. THere is virtually no evidence whatsoever, that using pharmaceutical grade drugs would improve animal welfare or science. This is another instance of an attempt to implement a strategy that, on the surface may sound reasonable but, in reality, is completely without benefit to animal welfare. Moreover, the costs incurred are substantial - again, reducing funds available for meaningful research, delaying productivity and increasing the burden of extraneous activity to our investigators.


Comment 2:
OLAW should require any institutional compliance with the new Guide not sooner than 2015.

62 04/14/2011 at 04:10:49 PM Organization University of Maryland School of Medicine Baltimore, Maryland Comment 1:
Adoption of this Guide is unnecessary and amounts to a total waste of precious federal research funds. There are no scientifically valid studies indicating that the health or welfare of the animals would be improved by adoption of the new guidelines. But the new Guide would definitely translate into significantly greater costs (cages!! et al.). A cynic may wonder if this initiative was sponsored by cage manufacturers and alike.... We are supposed to make best use of taxpayers' money, especially in the current fiscal climate. This initiative does the exact opposite. It's simply a terrible idea.


Comment 2:
Yearly inspections are entirely adequate. Do not fix something that is not broken. Again spoken as a cynic: is this initiative meant to provide jobs for inspectors?? What other purpose could there be?

63 04/14/2011 at 04:17:38 PM Self University of Maryland, Baltimore Baltimore, MD Comment 1:
This new caging policy for rodents is arbitrarily defined and is not correct according to recent studies. For example, the article given below finds that "The current findings indicate that mouse housing density can be increased 50% to 100% above the current recommendations (as floor area per mouse) with no or few apparent affects on mouse overall wellbeing."

The intended guide will result in the following: · No more than 4 (not the 5 currently allowed) adult mice per cage – this represents a 20% increase in cages needed over current standards · A female with litter would have to be housed individually, since there would only be 12 sq. in. remaining (63 sq in/cage – 51 sq in for mom with litter) – not "enough" space for a second adult mouse (which needs 15 sq in per these requirements). For a "standard" 2 female, one male breeding cage (which can currently remain together in a single cage as the females deliver pups and nurse them) this represents a >200% increase in cages needed over current standards.

Therefore, to increase research costs without justification or scientific validity is a waste of resources, especially in such a budget restricted time.

J Am Assoc Lab Anim Sci. 2009 Nov;48(6):740-53. The response of C57BL/6J and BALB/cJ mice to increased housing density.

Nicholson A, Malcolm RD, Russ PL, Cough K, Touma C, Palme R, Wiles MV.

The Jackson Laboratory, Bar Harbor, Maine, USA.

Abstract

Increased numbers of mice housed per cage (that is, increased housing density) is seen as 1 way to reduce the costs of conducting biomedical research. Current empirically derived guidelines are based on the area provided per mouse depending on body weight as documented in the Guide for the Care and Use of Laboratory Animals. The current study aimed to provide a more scientific basis for housing density by examining the response of C57BL/6J and BALB/cJ mice to increased housing density from weaning to 5 mo of age, to determine those parameters most useful for future larger-scale studies. A wide range of phenotypic characteristics--including growth rate, body composition, hematology, serum biochemistry, hormone and metabolite measurements, in-cage telemetry, behavior, and cage microenvironment--was examined at various time points. The parameters showing greatest changes were: growth rate, which was significantly reduced in animals at the highest density; adrenal gland size, the proportion of adrenal cortex, and concentration of fecal corticosterone metabolites, all of which were increased at higher densities; and anxiety and barbering, which were more pronounced at higher densities. Cage microenvironment deteriorated with increasing density, but the increases in measured parameters were small, and their biologic impact, if any, was not apparent. The current findings indicate that mouse housing density can be increased 50% to 100% above the current recommendations (as floor area per mouse) with no or few apparent affects on mouse overall wellbeing. However, weight gain, fecal corticosterone metabolite levels, and barbering differed significantly with housing density and therefore are suggested as good measures of the response to alterations in housing.


Comment 2:
This new caging policy for rodents is arbitrarily defined and is not correct according to recent studies. For example, the article given below finds that "The current findings indicate that mouse housing density can be increased 50% to 100% above the current recommendations (as floor area per mouse) with no or few apparent affects on mouse overall wellbeing."

The intended guide will result in the following: · No more than 4 (not the 5 currently allowed) adult mice per cage – this represents a 20% increase in cages needed over current standards · A female with litter would have to be housed individually, since there would only be 12 sq. in. remaining (63 sq in/cage – 51 sq in for mom with litter) – not "enough" space for a second adult mouse (which needs 15 sq in per these requirements). For a "standard" 2 female, one male breeding cage (which can currently remain together in a single cage as the females deliver pups and nurse them) this represents a >200% increase in cages needed over current standards.

Therefore, to increase research costs without justification or scientific validity is a waste of resources, especially in such a budget restricted time.

J Am Assoc Lab Anim Sci. 2009 Nov;48(6):740-53. The response of C57BL/6J and BALB/cJ mice to increased housing density.

Nicholson A, Malcolm RD, Russ PL, Cough K, Touma C, Palme R, Wiles MV.

The Jackson Laboratory, Bar Harbor, Maine, USA.

Abstract

Increased numbers of mice housed per cage (that is, increased housing density) is seen as 1 way to reduce the costs of conducting biomedical research. Current empirically derived guidelines are based on the area provided per mouse depending on body weight as documented in the Guide for the Care and Use of Laboratory Animals. The current study aimed to provide a more scientific basis for housing density by examining the response of C57BL/6J and BALB/cJ mice to increased housing density from weaning to 5 mo of age, to determine those parameters most useful for future larger-scale studies. A wide range of phenotypic characteristics--including growth rate, body composition, hematology, serum biochemistry, hormone and metabolite measurements, in-cage telemetry, behavior, and cage microenvironment--was examined at various time points. The parameters showing greatest changes were: growth rate, which was significantly reduced in animals at the highest density; adrenal gland size, the proportion of adrenal cortex, and concentration of fecal corticosterone metabolites, all of which were increased at higher densities; and anxiety and barbering, which were more pronounced at higher densities. Cage microenvironment deteriorated with increasing density, but the increases in measured parameters were small, and their biologic impact, if any, was not apparent. The current findings indicate that mouse housing density can be increased 50% to 100% above the current recommendations (as floor area per mouse) with no or few apparent affects on mouse overall wellbeing. However, weight gain, fecal corticosterone metabolite levels, and barbering differed significantly with housing density and therefore are suggested as good measures of the response to alterations in housing.

64 04/14/2011 at 04:21:27 PM Self     Comment 1:
I oppose adopting the 8th edition of the Guide, in part because many of the proposed changes that are purported to be for the benefit of the animals are not supported by any scientific evidence. For instance, I am not aware of any evidence to support the changes in rodent housing standards, or of any evidence suggesting that the health or well-being of laboratory rodents is at all compromised by use of the existing (7th edition of the Guide) housing standards. While any consideration of costs should be secondary to the primary concern for animal welfare, it is irresponsible to require costly changes to care that have no demonstrable benefit to the animals.


65 04/14/2011 at 04:26:42 PM Self     Comment 1:
The new guideline requires an increase in floor spaces for a mouse 25 grams and over (15 sq. in.) and for a female mouse with a litter of pups (51 sq. in.). It is still highly controversial if this increased floor space will increase animal health and wellbeing. However, they represent an unnecessary financial burden on everyone who uses or cares for rodents in research. The money from a typical R01 is not sufficient to pay the cage charges at the current funding level. With the worsening funding environment, I thought that available money should be spent on advancing research, and not on buying new cages for a perceived (but scientifically unproven) increase in animal well being.


66 04/14/2011 at 04:29:23 PM Self     Comment 1:
There is much concern from the researchers in the department that the changes are expensive and will do nothing to promote the health and well-being of animals.


67 04/14/2011 at 04:52:07 PM Self     Comment 1:
Retain the 1996 Guide as is. Restrictive policies on science and innovation should be based on valid scientific evidence. The requirement to use only pharmaceutical grade chemicals for all species is particularly absurd.


Comment 2:
Retain the 1996 Guide as is. Restrictive policies on science and innovation should be based on valid scientific evidence. The requirement to use only pharmaceutical grade chemicals for all species is particularly absurd.

68 04/14/2011 at 04:56:56 PM Self     Comment 1:
I would like to express my concern about some of the changes that are planed for this last edition. Space. I am a mouse user and, long story short, these changes will result in being able to hold just 4 mice per cage instead of 5, which results in a considerable increase on the per diem costs and space. As it is mentioned in the document, this particular change is based in recent studies that, at the end of the day, do not prove anything due to the variabilities in those studies. I have being using different strain of mice for over 6 years and I can see that 5 animals do well as long as the cages are changed at the proper time and that, fights rarely occur if you do not try to mix adult animals from different cages. And, if agressivity has to happen, it does not matter if there are 2 or 5 animals housed. If we are to reduce to 4 the animal to house per cage, we will need too many cages to reach a scientifically significative number for our studies and for what? Because it is not that rare that an experimental animal dies during the study and that particular cage is left with 4 instead of 5 animals. Does that mean that my results are influenced by the fact that the animals from the cage with 4 animals had more space and therefore their mental health was better...? I truly think that, to introduce a change with such an impact, you cannot just base it in a possibility, you really need to justify it with real prove. Thanks


69 04/14/2011 at 04:59:04 PM Self   Richmond VA Comment 1:
No--I recommend that NIH not adopt the New Guide.

My rationale for this recommendation is based on multiple factors that include:

-the financial and administrative cost of complying with new regulations and the resulting disruption in research

-the burden of guidance to either use pharmaceutical grade chemicals or to justify not using them, despite a lack of evidence to suggest that pharmaceutical grade chemicals improve animal welfare or science

-vague language subject to multiple interpretations on many issues such cage sizes, use of restraint, and use of food restriction


Comment 2:
Implementation should be delayed until at least March 2015.

My rationale for this recommendation is based on my view of the extensive revisions promulgated by the New Guide and the extensive changes in research procedures, administrative procedures and infrastructure that will be required to comply with the New Guide.

70 04/14/2011 at 05:07:10 PM Organization Columbia University Psychiatry and the NYS Psychiatric Institute New York, NY Comment 1:
The new guide , if fully adopted by OLAW as policy would have SIGNFICANT SCIENTIFIC and ECONOMIC impact on our research. There has not been sufficient time to completely assess this impact and the space limitations for comments is too restrictive to allow meaningful feedback. For example, at our institution the new space requirements for mouse breeding would require new caging (major expense), or a change from social 'dam' housing (mice) to housing single dams with litter more space. The latter is a significant economic burden. The latter solution forces us to change an important aspect of our experimental design (social parenting) which we believe benefit our mice. Either solution will require more space, which, in turn requires major programmatic changes that may take years to complete. I think I speak for most investigators and our IACUC in strongly recommending that 1) more time be given for the scientific community to evaluate the impact of the guide and provide meaningful feedback.


Comment 2:
It is unlikely that institutions can implement all of the major changes (the 'musts') outlined by the guide by March 2012. It is recommended that NIH implement instead a 'evaluation period' in which institutions are encouraged to begin using the guide for evaulations and give feedback to NIH. During this time the current guide should be the basis for the official semiannual IACUC evaluation. As stated above, new policies based on the 8th edition would force major changes to experimental design, caging and/or the physical plant. Any implementation deadlines should be set with full consideration of the time needed to make these major changes.

71 04/14/2011 at 05:27:04 PM Organization University of Texas at Dallas Richardson, TX Comment 1:
No valid need exists for adopting the altered guidelines in the 8th edition of the guide for use of laboratory animals. Exacerbating this lack of validation is the fiscal (financial) climate under which research must exist: stringent budgetary and space limitations. With the current political climate, it seems incredible to ask institutions to make vast new expenditures for new animal housing and/or to cut the number of experiments performed to meet arbitrary new requirements. Our own facility is only two years old, and all new caging and equipment was purchased at that time. Are we to throw away this large investment (which should be amortized over a decade or more) and begin anew, at a higher cost to every investigator on the entire campus? Or are we required to increase per diem costs, effectively reducing the yield of every single publicly funded research project? That hardly seems the route to fiscal responsibility both political parties propound currently. Our ACUC strongly recommends against ANY such new regulation.


Comment 2:
NO to adoption of the new 8th edition!

Leave current guidelines in place as they stand; veterinary staff at the local level are more than well qualified to make additional recommendations!

72 04/14/2011 at 05:59:40 PM Self     Comment 1:
I do not favor adopting new requirements. The requirements of the previous version are sufficient to ensure appropriate care and use of laboratory animals.


Comment 2:
I do not favor adopting new requirements. The current requirements are sufficient to ensure appropriate care and use of laboratory animals.

73 04/14/2011 at 06:01:21 PM Self     Comment 1:
I am opposed to the adoption of these standards and particularly those requiring increased space for housing rats and mice. These standards are unnecessary and will divert resources from the actual research.


74 04/14/2011 at 06:03:22 PM Self University of Maryland School of Medicine Baltimore, MD Comment 1:
I am writing about the changes in the "Guide" regarding husbandry for mice. The requirement it proposes to provide more space per mouse, and per dam and her litter, would be very costly. At my institution, it would increase my costs for the mouse colonies I maintain by at least 25%. That is the equivalent of half a technician's salary, and would make it impossible for me to maintain my research program and research staff at its current size. Across all universities and research institutions in the country, this change alone would result in the loss of thousands of good research jobs and the significant shrinking of programs that use murine models of human diseases. This would in turn undermine the efforts of the NIH to promote translational research, slowing the development of new therapeutics. In a time of diminishing federal research dollars, this is just about the worst thing you could contemplate doing. I urge you to find an alternative (in my opinion, there is nothing wrong with our current approaches to animal husbandry for rats or mice), or at the very least to postpone implimentation of the new regulations until the federal research budget is growing again.


75 04/14/2011 at 06:39:26 PM Self     Comment 1:
I am VERY STRONGLY OPPOSED to adoption of the 8th edition of the Guide. Most important: there is NO Scientific Evidence that rodents will be SIGNIFICANTLY better off in terms of health and wellbeing with the proposed new caging guidelines. The increassed cost, which is therefore not justfied, will be enormous at a time when funding for research is decreasing. Our entire bioscience research enterprise is already in jeopardy; adoption of these proposed guidelines would further damage the entire enterprise.


76 04/14/2011 at 09:45:42 PM Self u of maryland dept of orthopaedics, school of medicine baltimore, MD Comment 1:
The increased space requirements for housing mice and rats would seem to have little scientific backing in the way of proof of improved health and well-being of the animals, yet add substantial increases in cost to house the animals during a time of constricted research funding.


77 04/14/2011 at 10:10:11 PM Organization University of Hawaii Laboratory Animal Service Honolulu, HI Comment 1:
This is a significant guidance document which requires more time and space for comment by the public.


78 04/15/2011 at 03:13:41 AM Self Virginia Commonwealth University Richmond, VA Comment 1:
No--I recommend that NIH not adopt the New Guide.

My rationale for this recommendation is based on multiple factors that include:

-the financial and administrative cost of complying with new regulations and the resulting disruption in research

-the burden of guidance to either use pharmaceutical grade chemicals or to justify not using them, despite a lack of evidence to suggest that pharmaceutical grade chemicals improve animal welfare or science

-vague language subject to multiple interpretations on many issues such cage sizes, use of restraint, and use of food restriction


Comment 2:
Implementation should be delayed until at least March 2015.

My rationale for this recommendation is based on my view of the extensive revisions promulgated by the New Guide and the extensive changes in research procedures, administrative procedures and infrastructure that will be required to comply with the New Guide.

79 04/15/2011 at 04:54:50 AM Organization MPI Research Mattawan, MI Comment 1:
I strongly urge the USDA adn OLAW to NOT adopt the newest animal guidelines. The additional expense to our institutions and to the pharmaceutical industry with no real enhancement of animal welfare is just one reason NOT to adopt these guidelines. The additional paperwork burden to the investigator and the institution is yet another.


Comment 2:
All active researchers are concerned that: (1) the 2011 Guide contains many recommendations that will, in effect, function like regulations, rather than the "guidelines" for the care and use of research animals authorized by the Health Research Extension Act of 1985; (2) there is insufficient scientific evidence for some revisions reflected in the new Guide; and (3) the additional provisions of the 2011 Guide will have a significant economic impact on all PHS-assured institutions as well as the Contract Research Organizations that conduct such research on behalf of pharmaceutical industry sponsors. We do NOT want these guidelines finalized or adopted by the USDA or OLAW.

80 04/15/2011 at 06:07:01 AM Self     Comment 1:
I am strongly opposed to the recommendations which are not based on good science, are not peer reviewed, and will result in a vast increase in costs without benefit. This is a waste of research money and will have significant effects on the research infrastructure of the USA and further erode the productivity and preeminence of the USA research investment and competitiveness.


Comment 2:
I am strongly opposed to the recommendations which are not based on good science, are not peer reviewed, and will result in a vast increase in costs without benefit. This is a waste of research money and will have significant effects on the research infrastructure of the USA and further erode the productivity and preeminence of the USA research investment and competitiveness.

81 04/15/2011 at 08:07:09 AM Self     Comment 1:
My understanding is that the new "Guide" will be twice the size of the old guide. I wish to register my opposition to any increases in the regulation of animal research. I also request that existing regulations be modified so as to reduce the disabling burdens they place upon biomedical researchers who are trying to cure diseases that cause human and animal suffering.

Biomedical researchers who use animals in their research are already suffocating in a litany of regulations that range from practical to absurd. Many of these regulations are attributable to animal rights extremists who misrepresent animal research as torture. To move in the direction of abolishing all animal research, they have been able to promulgate their falsehoods to a sufficiently large number of activists who have lobbied congress successfully to impose regulations that cripple the ability of biomedical researchers to develop cures for diseases that afflict both humans and animals.

More enlightened countries such as Singapore are capable of discerning truth from hyperbole. This is why they are becoming a Mecca for biomedical researchers and we are beginning to see a brain drain from the United States.

Several years ago Philip Zimbardo conducted the infamous "Stanford Prison Experiment" which had to be stopped prematurely after only 6 days because of the sadistic abuse of "prisoners" by their "guards". I submit that today's IACUC committees by virtue of the unrestricted powers they have been given, have become the 21st century "guards" and that biomedical researchers have become the "prisoners". Clearly IACUCs are not working as intended and their powers to subject biomedical researchers to their irresponsible whims should be severely curtailed if not completely abolished.


Comment 2:
I oppose this additional regulation because it adds an unreasonable, disabling burden to institutions that are working for the common good.

82 04/15/2011 at 08:48:08 AM Self     Comment 1:
I am writing about the changes in the "Guide" regarding husbandry for mice. The requirement it proposes to provide more space per mouse, and per dam and her litter, would be very costly. At my institution, it would increase my costs for the mouse colonies I maintain by at least 25%. Across all universities and research institutions in the country, this change alone would result in the loss of thousands of good research jobs and the significant shrinking of programs that use murine models of human diseases. This would in turn undermine the efforts of the NIH to promote translational research, slowing the development of new therapeutics. In a time of diminishing federal research dollars, this is just about the worst thing you could contemplate doing. I urge you to find an alternative (in my opinion, there is nothing wrong with our current approaches to animal husbandry for rats or mice), or at the very least to postpone implementation of the new regulations until the federal research budget is growing again.


83 04/15/2011 at 09:16:14 AM Self     Comment 1:
I am opposed to NIH adopting the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals. The new rules on rodent housing were apparently largely derived from European housing standards and it is highly controversial if the adoption of these standards will increase animal health and wellbeing. They represent an unnecessary financial burden on everyone who uses or cares for rodents in research. In the current funding environment, available money should be spent on advancing research, not buying new cages for a perceived (but scientifically unproven) increase in animal wellbeing.


84 04/15/2011 at 09:49:38 AM Self     Comment 1:
The proposed schanges, primarily derived from European housing standards, are highly controversial. I am not convinced at all that these standards will increase animal health and wellbeing. They represent an unnecessary financial burden on everyone who uses or cares for rodents in research. In the current funding environment, available money should be spent on advancing research, not buying new cages for a perceived (but scientifically unproven) increase in animal wellbeing. I highly recommend re-evaluating this propsal with a clear mind seriously considering the current situation of our economy!!!!


85 04/15/2011 at 10:25:12 AM Self     Comment 1:
The Eighth Edition of the Guide contains substantive changes and additions to the previous edition. The limited opportunity for comment was simply insufficient in terms of both time and substance. A meaningful process for public input should be required. As indicated in the supplementary background information in the subject Federal Register notice, since 1985, the PHS Policy on Humane Care and Use of Laboratory Animals (PHS Policy) has required that institutions receiving PHS support for animal activities base their animal care and use programs on the current edition of the Guide and comply, as applicable, with the Animal Welfare Act (AWA) and other Federal statutes and regulations relating to animal activities. The PHS Policy was authorized by the Health Research Extension Act of 1985 (P.L. 99-158; 42 U.S.C. 289d) and is incorporated by reference in a listing of "several other HHS policies and regulations" that apply to grants for research projects (42 C.F.R. 52.8 and 42 C.F.R. 52a.8). While the Guide itself is not included among the policies and regulations listed, it is specifically and repeatedly referenced in the PHS Policy. The Guide for the Care and Use of Laboratory Animals has been an essential laboratory animal welfare reference document since it was first published in 1963. The 2011 Guide includes new and expanded coverage of the ethics of laboratory animal use; components of effective animal care and use programs (regulations, policies and principles; program management; program oversight; disaster planning and emergency preparedness); housing, environment, and enrichment for terrestrial and aquatic animals; veterinary and clinical care as well as physical plant characteristics. The 2011 edition is over 200 pages, nearly double the length of its predecessor. It contains more than 40 statements about what institutions "must" do, including 29 newly-stated requirements. In addition, there are now approximately 660 recommendations incorporated in the Guide that PHS award seekers "should" do. The 2011 Guide (p. 8) defines "must" statements as "actions that are imperative and mandatory duty requirements." "Should" is said to mean "a strong recommendation for achieving a goal" noting that "individual circumstances might justify an alternative strategy." The current comment process which limits comments to 6,000 characters including spaces and requires comments be submitted by April 24, 2011 is simply insufficient to provide NIH with meaningful comments as to the impact of the Guide on institutional animal care and use programs. Based upon the input we have received from our members, their comments specifically on the recommended minimum cage sizes for rodents housed in groups as well as other provisions would far exceed this limit. When the comments are requested for the Guide under the requirements of OMB Bulletin No. 07-02: Final Bulletin for Agency Good Guidance Practices, no such limits should be in place. A. The new Guide will dramatically increase the cost of research animals. As previously expressed by the Laboratory Animal Breeders Association of North America in comments on the pre-publication version, the new Guide's breeding cage requirements will have a major impact on their businesses. They estimate their total initial capital investment for changes will be $494 million. Their recurring annual operating cost is calculated to be $155 million. These dramatic increases will be passed on in the form of higher research animal prices to their research institution customers, including the NIH intramural program. PHS grants as well as the NIH budget will be affected. B. PHS-assured institutions will incur increased costs for new caging and renovation of facilities. Many, if not most large research-intensive institutions, also breed laboratory rodents in-house. Based on a NABR inquiry, one large NIH grantee indicated the cost of the breeding cage change could range from $3 million to as much as $20 million depending on how the different cage sizes could be accommodated. Another estimated a cost of $6 million for retrofitting existing housing facilities. Some additional NABR member estimates were lower. However, the most common response was that officials simply have not had time to assess the best course of action and what the resulting expenses will be. NABR's concern is that, if even a portion of the more than 1,100 PHS-assured institutions are involved with rodent breeding, the capital investment required to continue their programs could be in the hundreds of millions of dollars. C. The new Guide will increase PHS grant expenses beyond the direct cost of laboratory animals. The cost of rats and mice will certainly increase as breeders pass on the additional cost of meeting the new recommendations for breeding cages. In addition, the per diem charged to principal investigators for animal care by PHS-assured institutions will increase. In order to meet these new recommendations, institutions will either need to change the existing caging systems or increase the number of cages in use, thereby increasing per diem charges. While the cost impact of addressing the many new and revised recommendations is unclear at this time, there are certain to be other costs associated with programmatic changes resulting from the new Guide that will be passed on to the investigators. D. Research capacity will be reduced. In order to comply with new cage sizes, some facilities will have no option but to reduce facility capacity. One member predicts the loss of 20-30% in breeding space capacity.


Comment 2:
There is insufficient scientific evidence for some revisions reflected in the new Guide. Scientific evidence is lacking for changes in at least one major subject, the "recommended minimum space" for animals by species (Tables 3.2 - 3.6). In the Preface of the 8th Edition, the Committee acknowledges that scientific information is insufficient when it comes to space and housing needs of laboratory species, yet still includes new recommendations that will have significant impact on the research community. While acknowledging that many variables must be considered when housing animals in the laboratory, the new Guide offers no justification from the scientific literature as to why minimum space recommendations have been changed and why specific increases in dimensions were selected. Because the minimum cage sizes are expressed in exact dimensions by species in the Guide, they amount to fixed engineering standards with which PHS-assured institutions must comply. While the 2 inch increase in the height of rabbit cages (Table 3.3) and several changes in non-human primate caging (Table 3.5) are a problem for some NABR members, it is the revision of minimum space for laboratory rodents (Table 3.2) that is causing the greatest concern. For the first time the new Guide indicates recommended space for a "Female + litter" for both rats and mice, specifying a floor area of 51 in2 (330 cm2) for the former housing group and 124 in2 (800 cm2) for the latter. This designation would exclude the current practice of housing rodent pairs (male and female) and trios (one male, 2 females) together continuously for breeding purposes in the standard cage used by most facilities. The new European Directive for the Protection of Animals Used in Scientific Procedures (2010/63/EU) indicates the same floor space requirements, but uses the term "breeding" cages for rodent pair/trio housing, thus permitting the practice of housing breeding pairs and trios in existing cages (See Attachment 1). Because the new Guide will require larger caging for standard breeding practices, PHS-assured institutions and NIH contractors will be faced with the prospect of replacing existing cages for breeding pairs and trios with larger cages. Further complicating the situation is the fact that the 2011 Guide states (p 60-61), "Floor space taken up by food bowls, water containers, litter boxes and enrichment devices (e.g. novel objects, toys, foraging devices) should not be considered part of the floor space." There are significant operational, logistical, physical plant and financial issues associated with these recommendations, which will be commented upon in more detail by individual institutions and commercial laboratory animal breeders. This rodent breeding cage issue was raised in comments on the pre-publication version of the Guide released in June 2010. The final version of the Eighth Edition published in January of this year, only added an asterisk to the title of Table 3.2 with the related note: "* The interpretation of this table should take into consideration the performance indices described in the text beginning on page 55." OLAW currently has a "frequently asked question" published on its website that leads us to believe that the flexibility of institutions to use performance based standards in determining a policy on cage size will be more limited than implied by the language beginning on page 55 of the Guide. The text of that posting appears below: May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density? - OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes, and expects institutions to use the Guide's engineering standards as a baseline. The Guide clearly states that the need for adjustments to the recommendations for primary space enclosures should be made at the institutional level by the Institutional Animal Care and Use Committee (IACUC) and should be based on performance outcomes. The Guide further identifies examples of performance indices to assess adequacy of housing, including health, reproduction, growth, behavior, activity, and use of space (Guide, pages 25-26). IACUC determinations of the need for adjustments in the space recommendations should be based on veterinary considerations or scientific justification relative to the nature of the protocol and its requirements. Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non-animal welfare considerations are not acceptable. IACUC approved deviations from the Guide must be clearly documented and reflect the scientific or veterinary justification relevant to the action. For example, the Guide notes that space allocations should be reviewed and modified as necessary to address individual housing situations and animal needs such as prenatal and postnatal care. One way to address housing for maternally dependent litters of mice and rats is to consider them as single entities with their parent(s) until the pups begin actively moving about the cage, at which point multiple parental/litter groups should then be housed according to housing conditions recommended in the Guide. Adoption of the new Guide as planned by OLAW is likely to have a significant economic impact on PHS-assured institutions. Given the fact that research institutions are already under extreme financial strain and NIH faces the possibility of a significant budget reduction in FY 2011 and beyond, this economic impact must be carefully assessed. Since rats and mice are utilized as a research model by the tens of millions, the proposed change in breeding cage size is likely to have a significant economic impact that may be reasonably anticipated to lead to an annual effect on the economy of $100 million or more and would also materially alter the budgetary impact of NIH grants.

86 04/15/2011 at 10:46:43 AM Organization University of Maryland School of Medicine Baltimre, MD Comment 1:
I strongly support the need to provide suitable living conditions for animals in our care, but I also believe that the proposed changes will produce only a slight enhancement of animal welfare at an extremely high cost (i.e., the cost/benefit ratio is not favorable). I therefore hope that some of these proposed changes will not be adopted. In particular rules relating to mice that would require no more than 4 adult mice per cage (instead of five), and a rule stating that each female litter would need to be housed individually instead of permitting a second litter to be present prior to weaning.


87 04/15/2011 at 10:50:23 AM Self     Comment 1:
I am writing to express my opposition to the proposed changes in rodent housing standards outlined in the 8th edition of the Guide for the Care and Use of Laboratory Animals. The new standards will impose an undue hardship on investigators whose research budgets will be reduced by a steep increase in per diem charges. I would urge the National Research Council to commission a scientific study to establish the benefit of these changes on animal welfare before implementing a policy change that will reduce our ability to conduct publically funded science.


88 04/15/2011 at 11:12:55 AM Self     Comment 1:
No.

There has been insufficient time for substantive public comment. Many people are just finding out about this. Some of the proposals are very troublesome. The suggested (I read mandated) increases in rodent cage sizes will cost a fortune to purchase new equipment. I do mouse genetics research and would probably need to reduce my activities by 1/3 to 1/2 to meet the costs of increased housing space, given constraints at my facility. There are many other changes that need serious discussion

*****


89 04/15/2011 at 11:37:06 AM Self   Richmond, Virginia Comment 1:
No, I recommend that NIH not adopt the New Guide


Comment 2:
No, implementation should be delayed until at least March 2015

90 04/15/2011 at 11:39:47 AM Self     Comment 1:
As a scientist who has been working with mouse models for many years, I strongly oppose some of the new regulations proposed by the Guide (8th Edition). For mice, the 8th edition of the Guide requires 15 sq. in. of floor space for a mouse 25 grams and over. A female mouse with a litter of pups requires 51 sq. in. of floor space. Our ventilated mouse rack cages provide 63 sq. in. of floor space. This means: • No more than 4 (not the 5 currently allowed) adult mice per cage – this represents a 20% increase in cages needed over current standards • A female with litter would have to be housed individually, since there would only be 12 sq. in. remaining (63 sq in/cage – 51 sq in for mom with litter) – not "enough" space for a second adult mouse (which needs 15 sq in per these requirements). For a "standard" 2 female, one male breeding cage (which can currently remain together in a single cage as the females deliver pups and nurse them) this represents a >200% increase in cages needed over current standards. I believe these new regulations will no doubt increase unnecessary costs for research and generate huge negative impact on our biomedical research, particularly under the current funding atmosphere.

I would also want to add some my personal note. For many years, I am confused by the fact that living expense on those mice in my lab is more than that for any person working in my lab including myself. My monthly animal bill is greater than my mortgage bill for the house where I live. And now, we are told that we did not treat mice well enough and we should offer more. As a human being, I want to stay in a luxury home and work in a luxury lab every day. However, the limiting factor is whether I can afford or not. The question is --- Can NIH afford the increasing costs while maintaining the same productivity? I think the priority for NIH right now should be helping researchers to cut down the costs while maintaining productivity, rather than further increasing their financial responsibility in research.


91 04/15/2011 at 12:33:20 PM Organization Univ. of Maryland Baltimore, MD Comment 1:
I believe that the changes to mouse cage housing are unwarranted by any scientific data and represent a new and unreasonable added cost to valuable scientific research. At a time when funding is difficult, these added costs make finding cures and treatments for diseases more difficult.

I have bred and cared for mice for over 20 years as a researcher. There is no basis for the increased area demanded by these new regulations.


92 04/15/2011 at 12:42:54 PM Self     Comment 1:
I acknowledge that the continuing efforts to ensure adequate attention to animal welfare are commendable. However, the proposed changes requiring increased space for housing mice represents an excessive burden on investigators. The new regulations will substantially increase animal care costs (calculated on a per-cage basis) in a time when NIH budgets and, consequently, grant budgets are being slashed. It is also not at all clear that the proposed changes will improve animal health and increase the humaneness of animals used for research.


Comment 2:
In addition to the added per cage costs, the additional administrative oversight will also add to research costs by necessitating increases in overhead budgets. While this is negotiated by OMB, the costs come from the increasingly strained NIH budget. This means less money for research and more for bureaucracy--another poor decision.

93 04/15/2011 at 12:52:47 PM Self     Comment 2:
I do not think that the benefits to the animals sufficiently justify the enormous increases in cost and effort required. Specifically the requirement individually house all female mice with litters will require immediate removal of cohabiting females or the male partner upon any birth and will thereby necessitate a large increase in cage number. And is this separation really preferable for - mice which as we know- are social animals? Lastly I think that any policy which requires a large increase in expenditures on animal care must be announced a year before implementation so that at least SOME grants can build this in (not most, but some).

94 04/15/2011 at 01:22:17 PM Self Boston College Chestnut Hill, MA Comment 1:
Please DO NOT adopt the eighth edition of the guide. The new rules will hamper animal research on rodents and A & S universities. New rules on survival surgeries, cage sizes, and in particular, the use of pharmaceutical grade drugs will have an extremely negative impact on research. Much neuroscience research depends on research grade drugs to manipulate the brain. Much of neuroscience research requires one survival surgery and one non-survival surgery (cardiac perfusion with formaldehyde).


Comment 2:
See above. The new rules are much too severe and will deter important health-related research.

95 04/15/2011 at 02:00:53 PM Self     Comment 1:
Is is a privilege to use animals in biomedical research, and we strive to provide the highest level of care for research animals. I believe the NIH should NOT adopt the eighth edition of the Guide, since it contains new guidelines for the housing of animals that are highly controversial. These changes, especially for the housing of mice, have not been proven to increase animal health and wellbeing.

However, they certainly will induce an unnecessary financial burden on everyone who uses or cares for rodents in research. In the current funding environment, available tax-payer money should be spent on advancing research, not buying new cages for a perceived (but scientifically unproven) increase in animal wellbeing.


Comment 2:
The NIH should NOT adopt the implementation plan using the eighth edition of the Guide. This edition of the Guide contains new guidelines for the housing of animals that are highly controversial. These changes, especially for the housing of mice, have not been proven to increase animal health and well being and will needlessly waste tax payer money.

They certainly will induce an unnecessary financial burden on everyone who uses or cares for rodents in research. In the current funding environment, available tax-payer money should be spent on advancing research, not buying new cages for a perceived (but scientifically unproven) increase in animal wellbeing.

96 04/15/2011 at 02:06:06 PM Organization Federation of American Societies for Experimental Biology Bethesda, MD Comment 1:
The Federation of American Societies for Experimental Biology (FASEB) appreciates the opportunity to comment on the National Institutes of Health's (NIH's) acceptance of the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide), as solicited by the announcement that appeared in the Federal Register on February 24, 2011. FASEB is a coalition of 23 life science societies representing more than 100,000 biomedical researchers, many of whom are involved in the humane use of animal models in research and education.

FASEB strongly supports deferring to the professional judgment of animal care staff in developing performance based standards that provide the best welfare for laboratory animals. Performance based standards are guiding principles that, while describing a desired outcome, provide flexibility in achieving that outcome by granting discretion to those responsible for managing the animal care and use program. Flexibility is important for providing optimal care to laboratory animals and ensuring the integrity of scientific research as it allows researchers, veterinarians, and animal care staff to take into consideration information on the species, individual animal, and research goals that may impact animal care and use. FASEB encourages NIH to follow the suggestions in the Guide and promote performance based standards and professional judgment.

Our specific comments concern two points: 1) Should NIH adopt the Guide as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service (PHS) support for activities involving animals? and 2) If NIH decides to adopt the eighth edition of the Guide, should NIH use it as the basis for evaluation by March 31, 2012?

1. FASEB recommends that NIH adopt the eighth edition of the Guide as a basis for evaluation of institutional programs receiving or proposing to receive PHS support for activities involving animals with the following caveats:

a. FASEB appreciates the importance of housing animals in cages appropriate for their physical, physiologic, and behavioral needs. In evaluating social housing needs for laboratory animals, we, again, strongly encourage NIH to place greater emphasis on performance based standards rather than engineering standards. Engineering standards are prescriptive and provide limited flexibility for implementation. For example, logistical barriers sometimes prevent social housing of animals. Odd numbers of animals needed for a particular experiment would leave one animal not pair-housed. In order to ensure all animals are socially housed, more animals than necessary would be utilized, which is inconsistent with the goal of reducing the number of animals used for research.

b. FASEB is particularly concerned about the new cage size requirements for rabbits and rodents. For example, FASEB finds that the change to a two-inch higher cage size for rabbits is especially troublesome. We suggest that the current rabbit cage sizes of 14 inches in height as defined in the 1996 Guide be maintained as opposed to the 16-inch standard in the 2011 Guide unless animals cannot make postural adjustments in the cages. In those cases, performance standards dictate that larger caging should be used. The rationale for increasing the height two inches is unclear, and it is uncertain whether this change would improve the quality of care for laboratory rabbits. Moreover, the current Animal Welfare Act standard is 14 inches in height. In the absence of a clear rationale, congruency between NIH and the United States Department of Agriculture should be maintained. This is consistent with President Obama's Executive Order 13563 and would reduce confusion and maintain efficient work-flow among researchers and institutions. In addition, imposing the new 16-inch standard will render current rabbit caging systems obsolete and necessitate a significant expenditure of funds by research facilities to replace this caging. The resulting expense in both equipment and administrative costs is not balanced by improvements in animal welfare.

In a change to rat caging standards, the 2011 Guide now requires that when the weight of paired rats increases to a point that they no longer meet the engineering standards of the Guide, they must be separated or moved to a larger cage. Individually housing these animals would conflict with the guidelines on social housing, yet meeting the new engineering standards set forth in the Guide would require a larger cage size, which is potentially problematic in terms of additional cost. Again, the fiscal constraints that institutions are under due to reduced NIH grant funding and reduced state support may make it difficult for institutions to implement the changes. It is important for NIH to provide clear guidance about what should be done in these cases. In addition, the 2011 Guide spells out specific cage size requirements for female rodents plus their litters, as well as other breeding configurations. Implementing these changes would add huge costs and reduce breeding capacity for many institutions. Again, performance standards should be paramount when evaluating cage spacing requirements.


Comment 2:
2. FASEB recommends that: 1) NIH delay the implementation of the Guide, and 2) NIH allow institutions time to develop a comprehensive plan that outlines implementation of new Guide regulations over a predefined period of time, if needed.

In order for institutions to implement the changes outlined in the new Guide, a concrete plan must be devised, which may include consultation with experts, hiring new staff, training existing staff, developing new standard operating procedures, and ordering and purchasing caging to meet new social housing and caging requirements. It will take a substantial amount of time to devise this plan, have it approved by the Institutional Animal Care and Use Committee (IACUC), and complete at least one semiannual program and facility evaluation. This process alone could take well over a year. Additionally, the budgetary constraints faced by research institutions and NIH may make it difficult for some institutions to implement the changes recommended in the new Guide by March 31, 2012. Therefore, FASEB recommends that the implementation date be March 31, 2013.

For institutions unable to implement all the changes at once in order to be in compliance with the new Guide, FASEB recommends they be allowed to develop and submit a plan to implement the necessary changes over a predefined period of time. This plan, for example, could state that an institution would replace all non-compliant cages over the period of four years (25% per year). As long as the institution meets the milestones outlined in the implementation plan, they would be considered in compliance with IACUC and the Office of Laboratory Animal Welfare. This strategy would allow institutions to prepare better for the financial challenges and infrastructural changes that would need to take place in order to be in compliance with the new Guide. This plan would need to be in place by March 31, 2013.

FASEB recognizes that humane animal care and high-quality science go hand-in-hand, and the biomedical researchers represented by FASEB take humane care very seriously. FASEB also appreciates NIH's commitment to providing guidelines that ensure the optimal care and welfare for research animals, and we thank you for this opportunity to provide comments. If you have questions or need additional information, please do not hesitate to contact us.

97 04/15/2011 at 03:40:02 PM Self     Comment 1:
NIH should not adopt the 8th edition of The Guide. In 2003, an ILAR document was published titled "The Development of Science-based Guidelines for Laboratory Animal Care" that presented the concept of using research and scientific principles to guide our policies on the use and care of animals, with utmost consideration on animal wellbeing. However, the 8th edition of The Guide does not advance the field of animal welfare by inclusion of scientific principles. It introduces policy that is based on philosophical arguments lacking basis on scientific findings. One policy that illustrates this is the new section on "Pharmaceutical Grade" reagents used in animal research (Ch. 2). What this section says is that "pharmaceutical grade" substances should be used, and if they are not used, this has to be justified, including a consideration of grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation, compatibility, and pharmacokinetics. This philosophy is not a new one, however, until now, it has not appeared in a policy document that would have a real impact on research institutions. There are several problems with this addition regarding "Non-Pharmaceutical Grade Chemicals and Other Substances." 1. The term "pharmaceutical grade" is not defined. 2. There are no scientific citations to reinforce this policy. Where is the evidence that non-pharmaceutical grade compounds, whatever they may be, are harming animal welfare or disturbing research results? 3. There is a misconception that this policy is actually part of the Animal Welfare Act. The paragraph cites a reference to USDA 1997b. This citation is a USDA Animal Care Resource Guide (www.aphis.usda.gov/animal_welfare/downloads/policy/policy3.pdf) that is not part of the Animal Welfare Act. It is a policy adopted by USDA to guide interpretation of the Animal Welfare Act, but it is not, in and of itself, part of the Animal Welfare Act. This USDA policy has language about non-pharmaceutical grade substances that is now showing up in The Guide. Again, the problem with this is that it's actually not part of the Animal Welfare Act, so it's not technically a federal law. It's simply the guidance USDA is providing in interpreting the Animal Welfare Act. Other groups could come up with alternative interpretations. Furthermore, this guidance provided by USDA still does nothing to define what is meant by "pharmaceutical grade". 4. The paragraph also cites Wolff et al 2003. This is a FAQ document that was published in Lab Animal in 2003. In the FAQ's specifically question 3 dealt with non-pharmaceutical grade compounds. This FAQ document was written by a group of veterinarians at OLAW. They are providing the argument that the use of non pharmaceutical grade compounds should be justified in an IACUC protocol. However, this response to an FAQ is not official public policy. It represents the opinion of veterinarians at OLAW. 5. The paragraph ends with a citation to NIH 2008. It is suggestive that this policy is part of NIH public policy. However, this is a reference document provided by the NIH to guide NIH internal research programs, and it does not apply to institutions funded by NIH. It is contains essentially the same verbiage found in the FAQ's cited above and the USDA guidance policy. (http://oacu.od.nih.gov/ARAC/documents/Pharmaceutical_Compounds.pdf) It does however provide some definitions, so it is a bit more helpful. A very important note: this document is not part of the Public Health Service Policy on Humane Care and Use of Laboratory Animals. To the best of my knowledge, the term "pharmaceutical grade" does not even appear in the PHS Policy on Humane Care and Use of Laboratory Animals. In fact, this reference to the NIH document appears to have been inadvertently left in the published form of the Guide, as a note in the "Addendum: List of Editorial Changes from the Prepublication Version" of The Guide indicates that this reference was removed from an earlier position in the paragraph: In summary The Guide relating to pharmaceutical grade compounds is misleading and confusing. It does not explain what is meant by pharmaceutical grade compounds, and it also suggests that using non-pharmaceutical grade compounds without justification goes against the Animal Welfare Act and PHS policy, of which it does neither. There has been an emphasis on the application of "science-based" guidelines to develop policies for the care and use of laboratory animals (e.g. see ILAR publication "The Development of Science-based Guidelines for Laboratory Animal Care, National Academies Press 2003). However, this policy on pharmaceutical grade compounds in research is not based on scientific principles, but rather a philosophical argument that, for some reason, non-pharmaceutical grade compounds (whatever that means) are inferior to pharmaceutical grade compounds (whatever they are). If the PHS adopts version 8 of The Guide, this policy will become PHS policy. We still don't even really know what this means. The PI would have to consider grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation, compatibility, and pharmacokinetics. Much of this already gets considered when preparing to administer a reagent to an animal. However, some information may not even be available. Do we have to send out research compounds to a compounding pharmacy or characterization lab? Will the PI have to do these characterizations in house? Does this policy apply to common practices such as administering sucrose in drinking water or using any chemical from Sigma or other reagent suppliers? How will drug dosage be adjusted? What about drug vehicles? Version 8 of The Guide should not be adopted by NIH. If a new version of The Guide is to be adopted, it should be based on scientific principles that will benefit animal welfare, and key terms should be defined.


Comment 2:
NIH should not adopt the 8th edition of The Guide. If implemented, facilities should not be required to use it in their semiannual inspections prior to March 31, 2015. It will take substantial time and effort to revise internal policies and procedures to meet the recommendation of the 8th edition of The Guide. This would be a multi-year process.

98 04/15/2011 at 05:03:43 PM Self University of Maryland School of Medicine Baltimore Maryland Comment 1:
I do not agree with the proposed changes in cage sizes for rodents, which are highly social species which seek out tactile contact with each other, live in small burrows and are in fact frightened by large open spaces. Increasing the size of the cages will do more to stress the animals than comfort them and could have severe and enduring negative consequences on research relevant to mental health


Comment 2:
Institutions are already under tremendous scrutiny and reporting demands for their use of animals and no beneficial purpose would be served by additional reporting, this would be a waste of taxpayers dollars.

99 04/15/2011 at 05:26:45 PM Self     Comment 1:
I spent a couple hours skimming over the 240 pages of the proposed 8th edition of the NIH Guide. Much of the changes are common sense. Some interpretations of the Guide come not from those with the goal of increasing animal welfare but rather with the goal of restricting and ultimately eliminating animal research. As such the vague and subjective wording in the document opens investigators and institutions to frivolous litigation. My other concerns are with requirements that would hinder rather than support animal health and welfare.

1) Of great concern is where the wording of must (defined by the guide as a requirement) is followed by something vague and subjective such as ensure the "well-being" of the animal or "provide a high quality of care and ethical standards" that could expose Universities and investigators to frivolous litigation from groups that would like to entirely eliminate animal research.

2) Under surgery it states that, "Careful monitoring increases the likelihood of successful surgical outcomes. Monitoring includes routine evaluation of anesthetic depth and physiologic functions and conditions, such as body temperature, cardiac and respiratory rates and pattern (Flegal et al. 2009), and blood pressure (Kuhlman 2008), and should be appropriately documented." I completely disagree with this statement. In rodents, successful surgical outcomes are best assured by clean, efficient surgeries that do not require supplemental anesthetic or longer exposure to gas anesthesia than necessary. Not only is it difficult to measure these physiological symptoms in rodents, doing so requires distraction from the surgery that increases anesthetic exposure and encourages breaks from aseptic technique.

3) The new mechanical standards do not appear to allow for a breeder male mouse to stay in the cage with the female and litter and appear to prevent harem breeding in most standard cages; hence they are in conflict with requirements elsewhere in the guide indicated that social animals should not be individually housed. They also state that environmental enrichment (e.g. a paper cup) is to be subtracted from available floor space without taking into consideration that the animal can walk or climb on it or carry it around. The new mechanical standards could greatly restrict research where space is at a premium and will require the employ of personnel who police this. It was better to have standards, e.g. the animal should be able to turn around in its cage and not touch the lid when situated in a normal position.

4) Under food restrictions the guide requires "the least restriction necessary to achieve the scientific objective." This is counter to studies which show rodents are healthier and live longer under food restriction (more than the least necessary to perform a task) than they do under ad libitum schedules. The guide again mandates that the "well-being" of the animals be monitored. This is vague and subjective. In addition, this section is written in a way that could be interpreted as though both food and fluid intake have to be monitored daily even if only one or the other is regimented. This could require a significant increase in personnel effort without increasing the safe monitoring of the health of the animals.

5) "Disaster plans should be established in conjunction with the respon¬sible investigator(s), taking into consideration both the priorities for triaging animal populations and the institutional needs and resources. Animals that cannot be relocated or protected from the consequences of the disaster must be humanely euthanized." This could be interpreted to mean in an impending disaster supporting the unnecessary death of animals and is in conflict with the 3Rs.

6) A good addition in the surgery section is that craniotomy could be considered a minor surgery where most have previously considered it opening a body cavity and classified it as major surgery. This makes sense given how quickly rodents recover from this type of surgery.


100 04/15/2011 at 09:43:06 PM Self     Comment 1:
I have several comments regarding the proposed guidelines for experimentation on wild/exotic animals. In the field of animal behavior research, guidelines based the biomedical model are often at odds with goals of basic behavioral research. Most animal behavior studies pursue experiments that do not involve intervention commonly performed in biomedical studies (i.e, do not involve pain) or only sets the occasion for natural behaviorl processes, such as predator/prey interactions. Unfortunately most animal behavior research suffers from low funding support; consequently, I argue that guidelines designed for domesticated/lab animals primarily used in biomedical research programs will limit the ability of many scientists to conduct basic animal behavior studies. Using novel species and allowing animals to behave in natural ways under laboratory conditions is fundamental to scientific discovery and it should not be smothered by blanket regulations on animal care and use that increases cost and oversight. Adoption of new policy should be postpone until the impact on animal behavior's unique approach, which is often beyond the knowledge of IACUC members, is fully considered.


101 04/16/2011 at 05:53:11 AM Organization UNIVERSITY OF CALIFORNIA DAVIS SACRAMENTO, CA Comment 1:
I do not believe that there is a compelling reason to adopt this new Guide which will cause increased expense and increased paperwork burden with no demonstrated benefit.


Comment 2:
There are numerous concerns regarding the new Guide. Of particular concern is the requirement to use pharmaceutical-grade chemicals. For the vast majority of academic research projects of the kind supported by NIH, there is no scientific advantage to using pharmaceutical-grade chemicals. There is also no benefit from an animal welfare perspective. However, this requirement will add enormous expense to procure pharmaceutical-grade chemicals that will reduce the availability research funds for other research needs. In addition to the waste of Federal funds, there will also be enormously increased administrative burden procuring such chemicals that will detract from time that could be spent on productive research.

102 04/17/2011 at 12:34:23 AM Self Virginia Commonwealth University   Comment 1:
No--I recommend that NIH not adopt the New Guide.

My rationale for this recommendation is based on multiple factors that include:

-the financial and administrative cost of complying with new regulations and the resulting disruption in research

-the burden of guidance to either use pharmaceutical grade chemicals or to justify not using them, despite a lack of evidence to suggest that pharmaceutical grade chemicals improve animal welfare or science

-vague language subject to multiple interpretations on many issues such cage sizes, use of restraint, and use of food restriction


Comment 2:
Implementation should be delayed until at least March 2015.

My rationale for this recommendation is based on my view of the extensive revisions promulgated by the New Guide and the extensive changes in research procedures, administrative procedures and infrastructure that will be required to comply with the New Guide.

103 04/17/2011 at 01:30:23 PM Self     Comment 1:
As a PI on several NIH grants that involve the use of non-human primates, I am particularly concerned with the additional regulations imposed by the new Guide. These regulations serve to impair our ability to make scientific decisions based on our experience and knowledge, and the questions we wish to ask. The amount of paperwork required to proceed with our best, experienced judgment presents a considerable burden, and may actually prevent our research from going forward if an unsympathetic or ignorant member of the IACUC decides to stop it. I use many non-pharmaceutical grade chemicals in my efforts to identify a treatment for drug abuse. The list of qualities to consider about these drugs is incompatible with this testing. What harm, for example, has been done in the past by the use of non-pharmaceutical grade compounds whose pharmacokinetics were not well understood?


104 04/18/2011 at 12:12:38 AM Self     Comment 1:
I do appreciate the thoughtfulness of the revised Guide. My chief concern, however, is that there is a shift in the document to emphasize administrative oversight over basic research. PIs are doing their best to enhance public health by conducting basic research under conditions of decreasing public funding and increased administrative burdens. While the new Guide helps by providing more detail for some animal care issues that have been vague in the past (e.g. cage sizes), some detail will actually have a likely negative impact on research productivity as more research dollars will need to be spent placating IACUC demands that may or may not enhance animal welfare (e.g. "should" for use of pharmaceutical grade compounds) vs. conducting studies that may lead to breakthroughs in understanding diseases relevant to public health.


Comment 2:
2012 is too soon for an institution (especially a small institution with minimal IACUC funds) to be able to prepare for implementation of the new Guide.

105 04/18/2011 at 08:36:59 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

106 04/18/2011 at 08:39:03 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

107 04/18/2011 at 08:39:12 AM Organization Harvard Medical School Boston, MA Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

108 04/18/2011 at 08:39:39 AM Self     Comment 1:
This guide should not be adopted. There are several problematic issues including the suggestion that pharmaceutical grade drugs should be used for animal studies.


Comment 2:
No, this version of the guide should not be used for any evaluation.

109 04/18/2011 at 08:47:51 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

110 04/18/2011 at 08:56:09 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

111 04/18/2011 at 08:58:18 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

112 04/18/2011 at 08:59:17 AM Self     Comment 1:
The new cage sizes are appropriate. We will not need to change anything in our facility. Having less than 11x11 inches for one rat would mean limiting its movement. Why are we against making welfare for the animals better? I hear that "it will cost much", but since when cost is a factor in welfare of animals? If this is best for the animals, it will also be best for our experiments and we will obtain data that are more relevant and interpretable if the welfare of the animals is appropriate, rather than inappropriate.


Comment 2:
We already do this in our facility, and tailoring it to the new guide would not be an additional burden. It is no big deal to do this semiannual evaluation, and it actually helps investigators. We find minor infractions and sometimes bigger ones. Why not correct them?

113 04/18/2011 at 09:01:46 AM Self     Comment 1:
NO.The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will significantly increase expenses to the institution and the investigator without really enhancing animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

114 04/18/2011 at 09:18:25 AM Organization University of Maryland School of Medicine Baltimore MD Comment 1:
Implementation of such a policy will immediately and directly affect our ability to perform research by driving up the cost of research and thereby decreasing the amount that is done.


Comment 2:
Implementation of such a policy will add extra administrative work and increase the cost of doing research.

115 04/18/2011 at 09:32:46 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

116 04/18/2011 at 09:33:42 AM Self     Comment 1:
Response:

NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
Response:

OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

117 04/18/2011 at 09:34:56 AM Organization Primates Incorporated (primatesinc.com) Madison, WI Comment 1:
Purpose of comment: To discuss and encourage retirement of animals from research by discussing case studies of success stories and methodology from researchers who already are retiring primates and other animals such as cats and dogs under their care

Given the fact that several researchers over the years have taken the initiative to plan to retire the primates under their care to sanctuaries, and adopt out dogs and cats involved in non-terminal studies, I am surprised that I could not find a discussion on primate retirement or laboratory animal adoption anywhere in The Guide.

I used to be a primate researcher for five years – while I worked there, I discovered how intelligent the rhesus monkeys were. I believe there are enough similarities between monkeys, chimps, and humans, that the monkeys deserve the same respect and accommodations as chimpanzees, including funding for their retirement whenever a retirement scenario arises.

I wrote the NIH several years ago about primate retirement and they told me they take primate retirement "very seriously". The reality is that the NIH only takes the retirement of chimpanzees seriously – not all primates. There is funding only for great ape retirement through the CHIMP Act, and inquiring about funding for retiring other primates (or even bringing up the possibility of retiring primates) can be frowned upon by senior management, and employees are easily intimidated and forgo the retirement option. Additionally, a research veterinarian told me that the NIH is using the 3Rs to justify continued re-use of primates over retiring them to reputable sanctuaries; they argue that retiring a monkey goes against the 3Rs. I believe this to be a negative interpretation of the 3Rs and think there needs to be a fourth R added to the 3Rs to avoid future confusion: Reduction, Refinement, Replacement, and Retirement

Admittedly, there are some sanctuaries that have had their problems – largely because of underfunding and lack of funding available for animal retirement. If funding is available from the research facility, it is for transportation and to build an enclosure, and the sanctuary is left providing and paying for the lifetime care of the monkeys which could likely cost $5 per day. Additional consideration to providing funding for the first year of care would be a drastic improvement and would ensure the monkeys would receive the quality care, space, and enrichment a sanctuary is supposed to provide. A quality primate sanctuary can be found if it is accredited by The Global Federation of Animal Sanctuaries or The American Sanctuary Association. Given the fact that there are researchers who are taking the initiatives to retire primates under their care, sanctuaries have and will continue to serve as a vital retirement resource.

As we continue to discover how smart primates are (e.g. we have recently confirmed Rhesus monkeys are self-aware), we need to start respecting them more by providing them with retirement options after their time in research. If primate researchers are justifying the use of monkeys because of their similarities to humans, shouldn't the monkeys be considered for primate retirement as chimpanzees are?

Sanctuary anecdotal evidence suggests abnormal behavior is drastically reduced if not relieved completely when a monkey is retired to a sanctuary with appropriate space, vegetation, social, and enrichment options. Primates who are not able to be rehabilitated through enrichment, social housing, or medication in the laboratory should be given a chance at primate retirement where research procedures are not present and the environment is much more accommodating to producing naturalistic behaviors. The primates with persistent abnormal behavior should not be re-used in studies – and especially not put in invasive terminal studies as a final way to use them. Please consider the brain chemistry involved in abnormal behavior and that using monkeys displaying abnormal behavior in brain chemistry studies should be discouraged and is likely an overlooked variable. The humane option is to treat monkeys with persistent abnormal behavior by giving them a chance at a more spacious, enriching, peaceful, and naturalistic environment. Indeed all primates, are deserving of primate retirement.

Please encourage the retirement of primates (or at least discuss retirement as an option) when the primates are not used in terminal studies or need special accommodations.

And please extend the CHIMP Act to cover all primates.

Thank you for your time and consideration.


Comment 2:
Please discuss primate retirement as a part of any animal-welfare training classes.

118 04/18/2011 at 09:37:29 AM Self   Boston MA Comment 1:
NO it should not.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

119 04/18/2011 at 09:38:22 AM Self     Comment 1:
My understanding is that the new "Guide" will be twice the size of the old guide. I wish to register my opposition to any increases in the regulation of animal research. To expand it further serves little need other than to mollify extremist animal rights groups intent on making biomedical research with animals so cumbersome that it will be nearly impossible to do.

I also request that existing regulations be modified so as to reduce the disabling burdens they place upon biomedical researchers who are trying to cure diseases that cause human and animal suffering. Biomedical researchers who use animals in their research are already suffocating in a litany of regulations that range from practical to absurd. Many of these regulations are attributable to animal rights extremists who misrepresent animal research as torture. To move in the direction of abolishing all animal research, they have promulgated falsehoods to a sufficiently large number of activists who have lobbied congress successfully to impose regulations that cripple animal research. As the parent of a child who died from an illness that might have been cured by now had it not been for the ability of extremist animal rightists to prevent the biomedical research needed to cure his and other children's diseases, I greatly resent the implementation of any additional impediments to animal research.

More enlightened countries such as Singapore are capable of discerning truth from hyperbole. This is why they are becoming a Mecca for biomedical researchers and we are beginning to see a brain drain from the United States.

I have a specific concern regarding Institutional Animal Care and Use Committees (IACUCs). I believe that they are now compromising biomedical research so badly that biomedical researchers spend more time dealing with trivial and often inane demands of IACUCs than they spend preparing grant proposals. Many years ago Philip Zimbardo conducted a psychological experiment in which some students simulated prison guards while others simulated prisoners. The experiment had such disastrous effects that it had to be terminated prematurely, after only 6 days, because of the harm it was doing to the "prisoners". I submit that today's IACUC members are the equivalent of the "guards" and that animal researchers are the equivalent of the "prisoners". I believe that IACUCs are so far out of control that it is only a matter of time before researchers begin to take legal actions against IACUC members who abuse their position on the IACUC causing damage to the careers of biomedical researchers and impairment of research to cure diseases.

Therefore I further recommend that any changes in the 8th edition of the "Guide" include a scaling back of the powers of IACUCs. Additionally, there should be a provision added to enable animal researchers to institute research misconduct proceedings against IACUC members whom they believe to be acting improperly. Additionally, explicit warnings should be given to IACUC members that they could be held legally responsible for improper conduct of their role in IACUCs.


Comment 2:
I oppose any additional regulations that would further hinder instutions conducting biomedical research from squandering scarce financial resources on regulations foisted upon our society by extremist animal rights groups whose ultimate goal is to stop biomedical research using animals.

120 04/18/2011 at 09:48:47 AM Self     Comment 1:
Please do not adopt this edition of the guide for the care and use of laboratory animals. We are over regulated as it is and this adds an additional unnecessary burden on the investigator. At this point the largest cost in any lab doing animal work is animal husbandry, these measures will further increase that cost and limit what can be done experimentally. At a time when science is falling behind in this country due to the previous administrations lack of funding it seems like a huge burden to further decrease our ability to do our work.


Comment 2:
Please push back the date to 2015 and gather empirical evidence that these measures would actually benefit anyone.

121 04/18/2011 at 10:01:39 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

122 04/18/2011 at 10:07:48 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

123 04/18/2011 at 10:11:51 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

124 04/18/2011 at 10:13:50 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

125 04/18/2011 at 10:19:16 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

126 04/18/2011 at 10:23:26 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

127 04/18/2011 at 10:51:16 AM Organization Mount Sinai School of Medicine New York, NY Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

128 04/18/2011 at 11:13:06 AM Self   Ann Arbor, Michigan Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

129 04/18/2011 at 11:32:15 AM Self     Comment 1:
ASPET urges OLAW not to adopt the 2011 edition of the Guide. Its deviation from the 1996 Guide will result in a significant increase in regulatory and paperwork burden and expense without benefit to animal welfare. ASPET supports the comments of NABR that were submitted to Francis Collins, Director of NIH. Our comments will focus on the newly added section "Use of Non-Pharmaceutical Grade Chemicals [NPC] and Other Substances," which adds new policy to the Guide that is unwarranted with respect to animal welfare or good research practice. Albeit well intended, this policy is not well informed regarding the conduct of research that uses drugs in laboratory animals. One problem with the new guidance on NPC is that the term "pharmaceutical grade" is not defined, nor does an accepted definition exist. An indication of its intended meaning is Guide citation of USDA/APHIS Policy 3, which covers "sedatives, analgesics, or anesthetics" used to prevent pain/distress with regulated species. Its use of "non-pharmaceutical grade" refers to medications not prepared for clinical use. The Guide extends Policy 3 terminology to all vertebrates and all chemicals used in research. The implication is that all solutions prepared by a researcher are considered of inferior quality and that clinical solutions are ideal for research, neither of which is accurate. Specifically, ASPET notes the following with respect to the four sentences on NPC in the Guide: (1) "The use of pharmaceutical grade chemicals. . .ensures that toxic or unwanted side effects are not introduced into studies. . . ." The use of commercially prepared solutions does not ensure this. There are many examples of commercial solutions being recalled. Mass manufacture of pharmaceutical grade drugs amplifies any error. (2) "They should therefore be used, when available, for all animal-related procedures. . ." The assertion that clinical formulations are superior for all-animal-related procedures is neither logical nor supported by scientific evidence. Laboratory-prepared formulations have been the norm in research for the last century. There is no evidence that research or animal welfare would be improved by changing this research practice. The way in which drugs are formulated for clinical use make them poor choices for research. For example, dose manipulations are essential to research. Unlike clinical use, volume of drug delivery needs to be held constant. The single concentrations of solutions sold commercially inevitably need to be diluted to manipulate dose. The assumed benefit of using a commercial solution are lost. Another element of good research is comparison of the effects of the drug with that of vehicle alone. Vehicles of commercial solutions cannot easily be duplicated. (3) "The use of [NPCs] should be described and justified in the animal use protocol and be approved by the IACUC. . . for example, the use of [NPC] may be necessary to meet the goals of a project or when a veterinary or human pharmaceutical-grade product is unavailable." The wording implies the need for an NPC is unusual. In reality, it is the rule. The vast majority of animal research involves compounds that are not used clinically. New chemical entities are key to advances in science and public health. Collaborations with academic, government, or industry chemists are common; many high purity compounds are available from highly regarded commercial sources. Drug supply programs at NIH make controlled substances and other compounds not formulated for use in humans available to researchers without cost, as do biotechnical and pharmaceutical firms. To require that each use of an "NPC" be justified in writing and reviewed and approved by an IACUC places an unwarranted paperwork burden on researchers and on the IACUC. (4) "Consideration should be given to the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation, compatibility, and pharmacokinetics of the chemical or substance to be administered, as well as animal welfare and scientific issues relating to its use (NIH 2008)." These considerations are applicable to veterinary care, but are of more variable relevance to research. A part of each research project that uses chemical compounds necessarily involves determining details of their use that will assure the meaningful characterization of the effects of the compound. ASPET suggests that requiring these to be spelled out in advance, and reviewed and approved by the IACUC singles out pharmacology research for micromanagement--a function that has not been the traditional goal or value of the Guide. Note also that the citation is to an intramural NIH guideline, which defines "pharmaceutical grade" differently than does USDA/APHIS Policy 3. In summary, the newly added Guide requirement to use drugs formulated for clinical use in research animals is not realistic. For the few situations in which such a drug might be available, the practical needs of research make them unsuitable, and the cost, compared to one suited for laboratory can be significant (e.g., up to 10-fold). To require NIH's drug supply programs to substitute clinical-use solutions for all those it currently provides via its drug supply programs would be an expense that does not justify use of scarce research dollars. Should OLAW adopt the 2011 Guide, ASPET urges that it consult NIH Institute Directors regarding the wisdom of including the NPC section as PHS Policy


130 04/18/2011 at 11:40:10 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

131 04/18/2011 at 11:42:52 AM Self     Comment 1:
I have a several concerns regarding the proposed new (8th) edition of the Guide, but my comments below are specifically limited to two of the guidelines on Food and Fluid Regulation (pp 30-31).

1. The proposed Guide states that "The objective… …should be to use the least [food and/or fluid] restriction necessary to achieve the scientific objective while maintaining animal well-being" (pp. 30-31). This view runs counter to both good science and established animal husbandry and care practice.

First, as noted in the publications cited in this section of the Guide, there is little or no evidence that moderate restriction protocols (e.g., in rodents, to 80-85% of free feeding weight for food restriction, or 24 hours for fluid restriction) have any adverse consequences under most circumstances.

Second, some degree of food restriction or limitation is common practice for most laboratory species (e.g. – rabbits, dogs, primates), not to mention for pets and zoo animals. Indeed, the absence of any sort of restriction seems only to be usual practice with laboratory mice and rats, for which free feeding seems to have developed as a matter of convenience for husbandry staff.

Third, there is ample scientific evidence across multiple species that long-term food restriction (e.g. – to 80-85% of free-feeding weight in rodents) confers significant health benefits, including longer life-span, fewer age-related diseases, and fewer neoplasms. In fact, even the Guide itself (Chapter 3, p. 67) describes the health benefits (even in mice and rats) of moderate caloric restriction.

Hence, based upon the work cited in the Guide itself, there appears to be no scientific evidence for (and ample scientific evidence against) the apparent assumption that any degree of restriction is negative.

2. The proposed Guide states that "In the case of conditioned-response research protocols, use of a highly preferred food or fluid as positive reinforcement, instead of restriction, is recommended" (pp. 30-31). This recommendation, although admirable in theory, runs counter to decades of scientific research and practice, which show that animals will rarely if ever learn and perform food- or fluid-motivated behaviors in the absence of some degree of restriction. This point is made strongly in two of the publications cited in this section of the Guide (Toth and Gardiner 2000; Rowland 2007). More practically, however, one could infer the fact that highly palatable foods or fluids are not effective motivational tools for behavioral studies in the absence of restriction simply from the fact that they are not used. Food/fluid restriction procedures are time-consuming and add additional administrative burdens, both of which drive up the costs of conducting research. If it were at all possible to avoid restriction procedures when conducting behavioral experiments in animals, then they would be avoided.


132 04/18/2011 at 11:48:54 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

133 04/18/2011 at 11:52:46 AM Self     Comment 1:
NO.

This is an emphatic NO. The new guide was originally supposed to be an "update" of the 1996 Guide--however the final product is 2x as long and contains a great deal of NEW "policy" that has not been properly vetted and is not supported by data.

Compliance with these NEW "policy" statements undoubtedly will greatly increase the expense of conducting public health research to both institutions (e.g., new requirements for cage size) and investigators (e.g., new constraints on the use of experimental drugs) without need. The scientific data justifying these expensive changes are non-existent. The policy changes laid out in the new Guide, if implemented, represent regulatory mischief that results in no real enhancement of animal welfare.

Adherence to the proposed 2011 Guide also will require large increase in paperwork (e.g., all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new Guide may also negate the opportunity to diminish the burden resulting from previous over-reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies will unduly increase infringement on scientific decision-making by PHS grantees, contractors and IRGs. Some specific examples of recommendations that are unwarranted by data include: constraints on multiple procedures in experimental subjects, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" that can be given to subjects under study, and specific guidance on "post-approval" monitoring (e.g., observation of procedures). Finally, the new "Guide" requires an increased level of intra and post-operative surgical procedures--again, without data indicating need.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. Those data alone should guide policy decisions.

134 04/18/2011 at 12:06:23 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

135 04/18/2011 at 12:18:59 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions

136 04/18/2011 at 12:55:35 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

137 04/18/2011 at 12:59:57 PM Self     Comment 1:
The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

138 04/18/2011 at 01:40:10 PM Self     Comment 1:
I have been a veterinarian for 25 years working in private practice, then becoming an emergency medicine clinician for 16 years and have now worked in laboratory medicine the past 7 years. I teach human handling classes, provide required veterinary reviews of animal use protocols for both our institution as well as for another institution and serve as a clinical veterinarian. During my time as a laboratory animal veterinarian, I feel I have been effective in improving researchers understanding that research animals are a small living environment rather than a petri-dish with legs. I have helped many understand that improvements in techniques, though some may take more time, are better for the animals well being or reduces their stress exposure and hence improve research efforts. I am a fervent believer in the application of the scientific method in that all practical efforts should be made to remove as many variables or subjective data related to determine accurate data related to the aims of the experiment. However I do not see or appreciate such scientific justifications for the proposed changes in the new GUIDE. There is apparent lack of logic in some of the changes proposed, such as the requirement in rabbit cage height. As written, thousands of cages would no longer be useable per the new requirement. If a scientific basis is provided to make such a change in additional height, it would be logical to set a weight value (or rump to head length measurement) to determine when larger cages are required to be used, just a mass value is assigned to caging for use with NHPs. This would allow many the current cages (most purchased with taxpayers dollars) to be used for rabbits smaller than the cut off weight for new height requirement. It is wonderful to consider changes for the well being of animals, but we should not do them based on personal opinions alone but rather based on scientifically proven benefit to animals health or well being ( given as they are used scientifically, this would be logical). If such changes as proposed in the Current Draft, are finally approved by PHS, a logical grace period should be given 1) Based on the current economic environment of our nation there are no magic dollars to make required changes rapidly for many institutions unless PHS plans to provide needed grants. 2) Changes may require more than just acquisition of 'new caging' but include major physical plant changes, new housing rooms be built, HVAC upgrades to meet human and animal health exposure requirements, none of which can be accomplished rapidly or often requireing over a year to implement.

If the panel that reviewed/ updated the new GUIDE can provide me with scientific data for the proposed changes, I would be happy to re-consider my stated views, otherwise let us not burden the taxpayer with changes that only make people 'feel better' as to the use of animals but provide no scientific benefit to the health or well being of those animals.


Comment 2:
As stated in my response to the prior section, many faclilities may require physical plant upgrades not just the purchase of new cages, hence if the draft of the NEW GUIDE is approved, I would suggest 2 year grace period before full implementation of the 'New GUIDES" requirements would be more logical given the current economic status of our country, unless PHS if willing to provide needed funding for any such neeeded facilities changes.

139 04/18/2011 at 01:56:35 PM Self     Comment 1:
The NIH should not adopt the 8th edition of the Guide for the Care and Use of Laboratory Animals. The new regulations are burdensome for investigators and add little to the welfare of laboratory animals. The previous edition is adequate.


Comment 2:
See above comment.8170

140 04/18/2011 at 02:31:48 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

141 04/18/2011 at 02:38:55 PM Self University of California Irvine Irvine, CA Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

142 04/18/2011 at 02:42:48 PM Self   Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

143 04/18/2011 at 02:54:15 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

144 04/18/2011 at 03:02:18 PM Self     Comment 1:
This letter is submitted in response to the National Institutes of Health's solicitation of comments concerning the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) that appeared in Federal Register on February 24, 2011 (76 Federal Register 10379 – 80).

While I support the use of the Guide as a document that promotes animal welfare while supporting the needs of the research community, I cannot support adoption of the Guide in its present form. The emphasis on performance based standards and professional judgment in much of the text is commendable, but I am concerned about new recommendations for rodent housing that 1) are not supported by scientific literature, 2) as presented appear to be fixed engineering standards, and 3) will have a significant financial impact on animal care and use programs that will be passed on to the investigators thereby limiting their ability to successfully complete research aims. During pre-publication review, the American College of Laboratory Animal Medicine commented that minimal cage size requirements for rodents presented in Table 3.2 of the Guide appear to be adopted from Annex II of the European Directive with a modification. In the European Directive an analogous table stipulates that mouse cages should provide 330 cm2 for each breeding pair with the qualification that a breeding pair is a "...monogamous pair (inbred/outbred) or trio (inbred)." Table 3.2 in the Guide however, calls for a minimum of 330 cm2 for a female with a liter plus 96.7 cm2 for each additional average sized adult mouse. Consequently, standard mouse cages used by facilities throughout the country are not large enough to house some rodent pairs (male and female) and all trios (one male, 2 females) typically maintained together for breeding purposes.

In the final version an asterisk was added to Table 3.2 with the related note: "* The interpretation of this table should take into consideration the performance indices described in the text beginning on page 55." However, this edit lacks the desired clarity since the discussion on performance standards that begin on page 55 continues to page 56 with a statement that reads, "space recommendations presented here….should be considered the minimum for animals housed under conditions commonly found in laboratory animal facilities". Moreover, one "frequently asked question" published on OLAW's website leads us to believe that the flexibility of institutions to use performance based standards to develop and implement a policy to house mice in configurations that result in less space than stipulated in the Guide is limited. The text of that posting appears below: May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density? - OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes, and expects institutions to use the Guide's engineering standards as a baseline. The Guide clearly states that the need for adjustments to the recommendations for primary space enclosures should be made at the institutional level by the Institutional Animal Care and Use Committee (IACUC) and should be based on performance outcomes. The Guide further identifies examples of performance indices to assess adequacy of housing, including health, reproduction, growth, behavior, activity, and use of space (Guide, pages 25-26). IACUC determinations of the need for adjustments in the space recommendations should be based on veterinary considerations or scientific justification relative to the nature of the protocol and its requirements. Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non animal welfare considerations are not acceptable. IACUC approved deviations from the Guide must be clearly documented and reflect the scientific or veterinary justification relevant to the action.

It is important to note the authors provide no scientific justification for the increased cage size requirement and in fact describe as insufficient the information that's available to delineate space and housing needs of laboratory species. By implementing the standards in the new Guide PHS-assured institutions will be forced to purchase additional cages or larger cages for breeding pairs and trios, which may required the purchase of additional racks, and in many instances, the construction of additional rooms to accommodate the increases. Alternatively, researchers would be forced to scale back breeding populations of inbred mice, thereby limiting research. Either way, NIH funded research facilities will incur substantial costs that could easily run into the hundreds of millions of dollars.

It is with great reluctance that I have decided that I cannot support the adoption of the Guide. If the Guide were adopted by the NIH, PHS-assured institutions would be forced to spend hundreds of millions of dollars to fully comply. These costs would be in large part be passed on to the investigators in the form of increased charges which would negatively impact their ability to maintain their currently level of productivity. Increasing the cost of doing animal based research without solid scientific evidence that such increases are needed is not consistent with the NIH's goal "to expand the knowledge base in medical and associated sciences in order to enhance the Nation's economic well-being and ensure a continued high return on the public investment in research."


145 04/18/2011 at 03:15:50 PM Self University of Maryland School of Medicine Baltimore MD Comment 1:
I am writing regarding the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals with specific reference to housing requirements for mice. I am fully supportive of maintaining animal health and well-being in a laboratory environment. However, it is not evident that the new guidelines that specify15 sq. in. of floor space per mouse have any basis in science or will in fact contribute to improved animal health and well being. In my institution each mouse cage has 63 sq.in. of floor space. Under the current guidelines that permit 5 mice per cage the proposed guidelines will restrict housing to 4 mice per cage and will only increase space per mouse by less than 20%. However, the increased costs of animal maintenance and facilities, in a time of reduced research funding will dramatically reduce the progress of research.

Furthermore, it will have a negative impact on breeding of mice needed for research. Currently we use a breeding scenario in which two females are maintained with one male. This permits the females to share care of the pups, a situation especially critical when one of the females is a novice and needs to learn how to care for the pups. Otherwise there is significant loss of newborns. The new guidelines require that a female with litter would have to be housed individually, since there would only be 12 sq. in. remaining (63 sq in/cage – 51 sq in for mom with litter) – not "enough" space for a second adult mouse (which needs 15 sq in per these requirements). Thus, I would predict more loss of new-borns and, therefore, a situation that is not compatible with maintaining animal health and well-being that is the purported intent of the new guidelines.

In addition, for a "standard" 2 female, one male breeding cage (which can currently remain together in a single cage as the females deliver pups and nurse them, and share care of the pups) this represents a > 200% increase in cages required over current standards with an associated increase in costs.

For these reasons I am opposed to these new guidelines for mouse housing which: 1-have no basis in science and 2-do not promise an increase in animal health and well-being and 3-will result in significant cost increases at a time of reduced funding.


146 04/18/2011 at 03:58:33 PM Self   Winston Salem, NC Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

147 04/18/2011 at 04:26:56 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

148 04/18/2011 at 05:24:19 PM Organization Washington University St. Louis, MO Comment 1:
Washington University in St. Louis is concerned about the substantive changes made to the Eighth Edition of the Guide for the Care and Use of Laboratory Animals.

The 2011 Guide contains many recommendations that will, in effect, function like regulations, rather than guidelines. At over 200 pages (nearly double the size of its predecessor) the 2011 revision includes new and expanded coverage of the ethics of laboratory animal use; components of effective animal care and use programs (regulations, policies and principles; program management; program oversight; disaster planning and emergency preparedness); housing, environment, and enrichment for terrestrial and aquatic animals; veterinary and clinical care as well as physical plant characteristics. It contains more than 40 statements directing what institutions must do, including 29 newly-stated requirements. In addition, there are now approximately 660 "strong" recommendations.

Although excellent new reference information from peer-reviewed scientific literature has been added in support of many subject areas, scientific evidence is lacking for changes in the recommended minimum housing space. In the Preface, the Committee acknowledges this deficiency, yet the new recommendations are still included. Of primary concern is the revision of minimum space for laboratory rodents: recommended space for a female and litter (mice) is 51 sq in and 124 sq in for rats. This would end the current practice of housing male/female rodent pairs and 1 male/2 female trios for breeding purposes in the standard cage used by most facilities.

These recommendations pose significant operational, logistical, physical plant, personnel and financial obstacles. To follow all the Guide's provisions to qualify for NIH awards, PHS-assured institutions will likely spend a minimum of $100 million annually for increased costs of research animals, per diems, new caging and facility renovations. Some facilities will have no option but to reduce facility capacity to comply with new cage sizes.

The limited opportunity for comment is insufficient in terms of both time and substance. A meaningful process for public input should be required. The current process limiting comments to 6,000 characters and requires comment submission by April 24, 2011 is simply insufficient to provide NIH with meaningful comments regarding the impact of this revision on institutional animal care and use programs. When comments are requested for the Guide under the requirements of OMB Bulletin No. 07-02: Final Bulletin for Agency Good Guidance Practices, no such limits should be in place.

Washington University in St. Louis recommends that NIH not adopt the new Guide until these concerns are addressed.


149 04/18/2011 at 05:29:21 PM Self     Comment 1:
This letter is submitted in response to the National Institutes of Health's solicitation of comments concerning the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) that appeared in Federal Register on February 24, 2011 (76 Federal Register 10379 – 80).

First, I would like to commend the Committee responsible for the 8th edition of the Guide on their significant effort in revising and updating the document to ensure that animal based research is conducted at the highest standard. With that said, I feel there is one significant change in the 8th edition of the Guide that has the potential to negatively impact animal based research, and as a result I cannot in good conscious recommend that OLAW adopt the Guide in its current format. More specifically, I am referring to the recommended cage sizes for female mice and rats with litters for which there is no scientific justification to support the recommendations.

To put things in perspective, the average mouse box provides approximately 66 sq. in. of floor space whereas the Maxi-cage made by some companies provides approximately 75 sq. in. of space. In either case, the current caging systems available for mice would only support a monogamous pair based on the floor space recommendations in the 8th edition of the Guide. Though the Guide does indicate that "the interpretation of this table (space recommendations for group housed rodents) should take into account consideration the performance indices described in the text beginning on page 55", I have significant reservations that OLAW, which tends to be prescriptive in nature, will be able to use performance standards, in lieu of the recommendations in Table 3.2. In my opinion, the table could work for AAALAC; however, I am not confident it will work for OLAW. As a result, I truly believe that this issue needs to be resolved prior to OLAW adopting the Guide and/or that OMB be asked to look at the impact of the new Guide on the research enterprise in the U.S.

The impact of the new recommendations for a female mouse with litter is significant. To move from a trio breeding system to a monogamous breeding system would have the following direct impact on the program for which I am associated: 1) the need to purchase an additional 6000 microisolator boxes; 2) the need to add 3 FTEs to the staff; 3) the need to add 5000 sq.ft. of animal housing space to the animal care program. The estimated cost to accommodate the new recommendations and go from a trio to a monogamous housing system would be approximately $2.2 million, of which a portion (new FTEs) would be recurring costs. The indirect impact would be greater cost to investigators for maintaining unique genetically engineered animals and a decrease in breeding indices. It is my belief, having worked in the field for over 23 years, that mice in trio breeding groups (1male/2females) have higher breeding indices, which may be attributed to a number of factors including: pheromone effects, social effects and shared parenting.

In conclusion, I would recommend that OLAW not adopt the Guide until the issue related to cage sizes for female mice and rats with litters is resolved. If OLAW and NRC cannot resolve this issue then I would also recommend that the document be made available for public comment and that OMB be asked to review the economic impact of the new Guide on the nation's animal based research enterprise.


Comment 2:
Institutions should be given 1 year from the date the 8th edition of the Guide is adopted by OLAW to complete at least one semiannual program and facility evaluation. Since March 31, 2011 has passed, I would recommend that March 31, 2012 not be used and that it be tied to the date (1 year following) approval by OLAW of the 8th edition of the Guide.

150 04/18/2011 at 05:38:12 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

151 04/18/2011 at 09:36:48 PM Self University of New England Biddeford, Maine Comment 1:
Comment 1: NIH requests public comments on whether it should adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals. Response: NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
*********************************** Comment 2: NIH requests public comments on NIH's proposed implementation plan which would require that institutions complete at least one semiannual program and facility evaluation using the eighth edition of the Guide as the basis for evaluation by March 31, 2012.

Response:

OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

152 04/19/2011 at 01:59:14 AM Self     Comment 1:
NIH should NOT adopt the new Guide. Several provisions will dramatically impede biomedical research. In particular, the provision that all drugs given to animals (even rats and mice) must be pharmaceutical grade is wrongheaded. This and other provisions will hurt drug discovery. They will also increase the cost of doing research, i.e., they will dramatically reduce research productivity, while having zero positive effect on animal welfare. At a time of catastrophic deficits, severe threats to NIH funding, and a true crisis in drug discovery, the adoption of these guidelines is the LAST thing the country needs. Please, let common sense prevail and reject this new Guide.


153 04/19/2011 at 07:47:29 AM Self   Philadelphia, PA Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements will increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, there is no scientific data justifying these expense changes. The new "Guide" policies increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

154 04/19/2011 at 09:14:39 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

155 04/19/2011 at 09:48:11 AM Self     Comment 1:
NIH should develop its own guide!!


Comment 2:
The new guide is developed mainly with the inputs of IACUC administrators and veterinarians, not so much from principal investigators

156 04/19/2011 at 10:24:49 AM Self     Comment 1:
I strongly recommend that the 8th edition of the Guide NOT be adopted. The new edition was originally intended to be an "update" of the 1996 Guide; however, the resulting document goes far beyond revision by invoking new restrictions that have not been adequately considered or discussed. Moreover, this edition is twice as long and contains new "policy" for which there is little or no empirical justification. Compliance with these new "policy" statements will increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs) without providing any clear benefit to research, the use and care of animals, to agencies funding this work, or to the public that benefits most from research. Most importantly, there is no scientific data provided to justify the proposed changes in "policy". Adherence to the 2011 Guide will require a large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already are "overregulated." Moreover, the new "Guide" policies infringe on scientific decision-making by PHS grantees, contractors, and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures. In summary, this edition of the Guide will seriously impede research activities without providing any clear benefit to any of the parties involved, including research animals.


Comment 2:
Institutional compliance with the new Guide should not occur before March, 2015 in order to allow for the collection of relevant data. These policies have been formulated without empirical support and any implementation of such a poorly concieved set of guidelines needs to be founded (or not) in information gathered over a broad range of conditions (institutions) and over several years of operation. Data, not opinion, should guide policy decisions.

157 04/19/2011 at 10:38:09 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

158 04/19/2011 at 10:39:03 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

159 04/19/2011 at 10:41:52 AM Self     Comment 1:
NO, DO NOT ADOPT THE EIGHTH EDITION OF THE GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS. This guide imposes unnecessary regulations that will hinder research, not improve it. the increased paperwork and expense are prohibitive and sufficient safeguards on the care and use of lab animals are in place.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

160 04/19/2011 at 10:49:22 AM Self     Comment 1:
These recommendations for housing of research animals, particularly those proposed for rodents and primates, lack scientific or ethical justification, and will impose a large and entirely unproductive burden on the research community. They should not be enacted.


Comment 2:
The seventh edition of the Guide should be retained, without alteration in current reporting requirments.

161 04/19/2011 at 10:55:06 AM Organization University of Maryland Baltimore, MD Comment 1:
The proposed new requirements for rodent and primate caging lack scientific justification. Further, there is no evidence that they will result in improved animal "well-being". Implementation of the new housing requirements would cost a tremendous amount of money without yielding any expected scientific or animal welfare benefit. This would be a huge waste of precious resources. Only if peer-reviewed objective data is subsequently produced that altered caging would likely result in improved animal welfare or more accurate scientific studies should revisions of this kind be reconsidered.


Comment 2:
The proposed 8th edition of the Guide should not be adopted, because the proposed new requirements for rodent and primate caging lack scientific justification. Further, there is no evidence that they will result in improved animal "well-being". Implementation of the new housing requirements would cost a tremendous amount of money without yielding any expected scientific or animal welfare benefit. This would be a huge waste of precious resources. Only if peer-reviewed objective data is subsequently produced that altered caging would likely result in improved animal welfare or more accurate scientific studies should revisions of this kind be reconsidered.

162 04/19/2011 at 11:00:13 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

163 04/19/2011 at 11:02:53 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

164 04/19/2011 at 11:03:06 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies increase infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will not enhance animal welfare but will result in significant additional expenses to the institute and investigators. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

165 04/19/2011 at 11:12:06 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions

166 04/19/2011 at 11:32:21 AM Self     Comment 1:
NO. The compliance with these new "policy" statements will increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

167 04/19/2011 at 11:39:52 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

168 04/19/2011 at 11:48:50 AM Self     Comment 1:
No, NIH should not adopt the eighth edition of the Guide. Although this edition was intended to be an update of the 1996 Guide, the final product is twice as long and contains a great deal of new policy, suggesting that the eighth edition of the Guide is more than an update. Compliance with new policy statements will increase expense to institutions (e.g., cage size) and to investigators (e.g., drugs). Importantly, scientific data supporting the need for these changes do not exist; thus, the additional expense to institutions and investigators will be incurred with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures and multiple surgeries in an individual animal, new requirements for food- or fluid-restriction, significant constraints on choices of "chemicals and other substances" given to animals, and specific guidance on "post-approval" monitoring (e.g., observation of procedures). Adoption of the eighth edition of the Guide will substantially increase in paperwork burden (i.e., all deviations from "should" statements contained in the new Guide will need to be justified) and negate the opportunity to diminish the burden resulting from over reactions to issues that are already "overregulated" by institutions. Moreover, policies in the new Guide will dramatically increase infringement on scientific decision-making by PHS grantees, contractors and IRGs.


Comment 2:
OLAW should require institutional compliance with the eighth edition of the Guide no sooner than March, 2015 to allow for the collection of relevant data, which should guide all policy decisions.

169 04/19/2011 at 12:22:44 PM Organization mount sinai new york, ny Comment 1:
The new regulations, if adopted, would place undue burden on animal research and greatly hinder our advancements. In addition,the specific recommendations included in this latest edition of the Guide for the Care and Use of Laboratory Animals are scientifically untested and extremely costly.


Comment 2:
Again, I'd forcefully add that the recommendations are scientifically untested and implementation of the regulations for facility evaluation by any date, but certainly by 2012, would place incredible financial strain on many struggling researchers and their institutions.

170 04/19/2011 at 12:28:12 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

171 04/19/2011 at 12:43:25 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

172 04/19/2011 at 01:10:39 PM Organization Wake Forest School of Medicine Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

173 04/19/2011 at 01:11:29 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

174 04/19/2011 at 01:12:15 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

175 04/19/2011 at 01:12:29 PM Organization Wake Forest University School of medicine Winston Salem, North Carolina Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

176 04/19/2011 at 01:15:28 PM Self   Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

177 04/19/2011 at 01:17:00 PM Organization Wake Forest School of Medicine Winston-Salem, NC 27157 Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

178 04/19/2011 at 01:23:27 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "over-regulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

179 04/19/2011 at 01:33:43 PM Organization Wake Forest School of Medicine Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

180 04/19/2011 at 01:33:58 PM Organization WFBH Winston Salem NC Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

181 04/19/2011 at 01:36:33 PM Organization Wake Forest University School of Medicine Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

182 04/19/2011 at 01:37:09 PM Organization Wake Forest University Health Sciences Winston-Salem, NC 27157 Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

183 04/19/2011 at 01:37:12 PM Organization Wake Forest Baptist Health Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

184 04/19/2011 at 01:39:45 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

185 04/19/2011 at 01:39:53 PM Organization Wake Forest University Health Sciences Winston Salem NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

186 04/19/2011 at 01:58:49 PM Organization Wake Forest School of Medicine Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

187 04/19/2011 at 02:06:02 PM Organization Wake Forest University Health Sciences Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

188 04/19/2011 at 02:12:52 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

189 04/19/2011 at 02:30:16 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

190 04/19/2011 at 02:36:31 PM Self     Comment 1:
NO. Please do not adopt the proposed 8th edition of the Guide. First of all, it goes way beyond what was originally recommened as an update to the 1996 edition and will increase costs associated with research for both researchers and institutions. Why these changes are being proposed is not based upon any scientific data and thus are not justified. The proposed Guide also infringes on the scientific decision-making process of PHS grantees, contractors, and IRG's in a number of significant ways. For example, it would insist upon the use of "pharmaceutical grade" drugs used in animal experimentation. There is no data to support this recommendation. Furthermore, this will drive up costs unnecessarily, and it is not clear how one is supposed to make the appropriate concentrations needed for experiments and maintain the "pharmaceutical grade" status of the preparation. Similarly, the constraints proposed on multiple procedures in animals, multiple surgeries, new requirements for food- or fluid-restriction, uninformed and constraining sections on the choices of chemicals and other substances, and specific guidelines on "post-approval" monitoring are not justified by any data or scientific rationale. The bottomline is that this new Guide seems to be driven by an animal welfare agenda and not based upon scientific data. Please do NOT adopt this proposed Guide unless you want to drive up the cost of research and kill the majority of medical research in this country.


Comment 2:
This new guide needs to go back to the drawing board and any proposed changes need to be based upon scientific data or deleted from the guide. Thus, it is my esitmate that this can not be done in less than a year, and I would propose that you do not require the use of any new guide until this is done. I suggest you shoot for something like an implementation date of March 31, 2015.

191 04/19/2011 at 02:45:48 PM Self     Comment 1:
I'm strongly opposed to the adoption of the 8th edition Guide.

The new guidelines requires more floor space per mouse in a cage, which limits the number of mice can be held per cage. This will increase the amount of cages needed to hold the same amount of mice, and increases the total price each lab pays to maintain the cages. In my lab, it would be a 20% increase in cost, just to maintain the cages, not to mention the cost of having to buy the extra cages. In addition, female mice with litters would have to be housed individually, according to the new space requirements. This in turn could even triple the number of cages needed. For rats, the new space requirements would also mean one female and litter per cage, again leading to many more cages needing to be purchased. Some labs may not have the physical space required in their facility to house more cages, which would cost even more.

I don't intend to sound greedy, as if this all has to do with money, but the money we have is best used towards our research, rather than accommodating new, scientifically unproven rules that may or may not support animal well being. The cost is too great for a benefit that is questionable at best.


192 04/19/2011 at 02:46:53 PM Organization Wake Forest Baptist Health Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

193 04/19/2011 at 02:47:02 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

194 04/19/2011 at 02:49:15 PM Organization Wake Forest University Health Sciences Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

195 04/19/2011 at 02:51:06 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

196 04/19/2011 at 02:51:33 PM Organization Wake Forest University Health Sciences Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

197 04/19/2011 at 03:02:16 PM Organization Wake Forest School of Medicine Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

198 04/19/2011 at 03:02:32 PM Organization Wake Forest School of Medicine Winston-Salem, North Carolina Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

199 04/19/2011 at 03:03:54 PM Organization American College of Neuropsychopharmacology Brentwood, Tennessee Comment 1:
The American College of Neuropsychopharmacology (ACNP), founded in 1961, is the nation's premier professional society in brain, behavior, and psychopharmacology research. The field of neuropsychopharmacology involves the evaluation of the effects of natural and synthetic compounds upon the brain, mind, and human behavior. ACNP welcomes this opportunity to comment on the question of whether the recently published 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as Public Health Service (PHS) Policy to govern all PHS-Assured institutions. Although the 8th edition contains useful new information (e.g., on the care of aquatic species), it otherwise represents a significant departure from the 7th edition in ways that impose new constraints, paperwork burdens, and costs on investigators and institutions receiving federal funds for research without a concomitant increase in animal welfare. ACNP therefore supports the position of the National Association for Biomedical Research (NABR) in its letter to Francis Collins urging that the NIH not adopt the new Guide until and unless concerns regarding new regulatory burdens are addressed. Although there are numerous new requirements in the 8th edition of the Guide that would impose substantial new paperwork burdens and expense, ACNP will focus in its comments on one issue of particular concern for its members. The new section on "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" adds a policy that, on the surface, may sound reasonable, but is inappropriate for basic research. Its apparent premise (based on the citation of an interpretive rule guiding USDA inspectors regarding adequate veterinary care) that the use of commercial drug solutions sold for clinical use in human or veterinary practice "ensures that toxic and unwanted effects are not introduced into studies conducted with experimental animals" is false. Not only do very few commercially available preparations exist that are suitable as tools for experimental research, but also, commercial solutions themselves are subject to formulation errors, as evidenced by recent recalls. Even with solutions that may be useful for a particular project, the need to conduct dose-effect evaluations inevitably means the commercial solution would need to be diluted or concentrated in the laboratory to accomplish this purpose. In addition, many commercial formulations, such as those in pill or capsule form, contain filler material that could confound experimental effects, especially when used by alternative routes of administration. For ACNP members, the ultimate goal of neuropsychopharmacology research is to find new treatments for neuropsychiatric illnesses. A critical step in much of this research is to give drugs with novel mechanisms of action to laboratory animals. Most of these drugs are, by definition, unavailable from commercial sources and must be prepared by the investigator. The requirement in this new section of the Guide that "The use of non-pharmaceutical-grade chemicals or substances should be described and justified in the animal use protocol and be approved by the IACUC," inappropriately presumes the accuracy of the premise that any preparation of drug solutions by the researcher can be assumed to be inferior to commercial preparation. The further requirement that "In such instances, consideration should be given to the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation compatibility, and pharmacokinetics of the chemical or substance to be administered, as well as animal welfare and scientific issues relating to its use. . " inappropriately defers the scientific judgment of the researcher to the IACUC. This recommendation also presumes that the IACUC has expertise, or retains someone with such expertise, to evaluate the details of formulations planned by the researcher. Review of the Guide indicates that this new section uniquely micromanages pharmacological research. In conclusion, the section on "non-pharmaceutical grade drugs" and multiple other sections of the new Guide preempt scientific and professional judgment on the design and conduct of research. This section seems especially inappropriate for a document that will govern the research of scientists whose funding has been granted based to a significant degree on the peer-reviewed determination of their expertise and ability to carry out specialized research. It goes significantly beyond the traditional value of the Guide for setting standards for animal housing, husbandry, and veterinary care of research animals.


Comment 2:
ACNP concurs with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, setting a date by which PHS-Assured institutions must comply with the new Guide prior to an OMB analysis of its financial impact on those institutions and NIH itself is premature.

200 04/19/2011 at 03:13:35 PM Self     Comment 1:
No, the Eighth edition ofthe Guide should not be adopted. This new guide was supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of what can only be called new "policy." Compliance with these new policy statements will increase the expense to institutions (e.g., changes in cage sizing) and expense to investigators (e.g., drugs). However, the scientific data justifying such changes is non-existent. The 2011 Guide will require a large increase in the paperwork burden (e.g., all deviations from "should" statements contained in the new Guide will now need to be justified). Adoption of the new guide may also negate the opportunity to diminish the regulatory burden resulting from reactions to issues for which institutions are already heavily regulated. Moreover, the new "Guide" policies constitute increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to institutions and to investigators with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" administered to to animals, and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra- and post-operative surgical procedures.


Comment 2:
The evaluation is to take place within one year of adoption of the new Guide. OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

201 04/19/2011 at 03:24:00 PM Organization Wake Forest University School of Medicine Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

202 04/19/2011 at 03:25:36 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

203 04/19/2011 at 03:36:37 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

204 04/19/2011 at 03:37:37 PM Organization Wake Forest University Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

205 04/19/2011 at 03:45:14 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

206 04/19/2011 at 03:46:51 PM Self Wake Forest University Department of Physiology and Pharmacology   Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

207 04/19/2011 at 04:02:02 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

208 04/19/2011 at 04:10:47 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

209 04/19/2011 at 04:13:09 PM Self     Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

210 04/19/2011 at 04:29:01 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

211 04/19/2011 at 04:32:02 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

212 04/19/2011 at 04:49:52 PM Organization Wake Forest University School of Medicine Winston-Salem, NC Comment 1:
The revised guide should not be adopted in its current form. The new guide was originally intended as an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

213 04/19/2011 at 05:23:49 PM Self     Comment 1:
I vote NOT to adopt. The new Guide is nearly twice as long as the 1996 version, and contains a great deal of new policy that promises to significantly increase: (a) the expense of research to investigators and institutions with no real enhancement of animal welfare, (b) the paperwork burden on researchers, and (c) the authority of local IACUCs to restrict already peer-reviewed research. And while some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food & liquid restriction).


Comment 2:
For the deadline for full compliance if the new Guide is adopted, I recommend at least 4 years (e.g., 2015) before requiring investigator and institutional compliance, given the expense of a variety of cage size and housing requirements that are being required at a time of great financial difficulty for investigators and research institutions.

214 04/19/2011 at 05:27:16 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

215 04/19/2011 at 05:32:56 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

216 04/19/2011 at 05:34:07 PM Organization Wake forest baptist scoop of medicine Winston Salem Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

217 04/19/2011 at 05:41:35 PM Self     Comment 1:
The new guide should not be adopted.


Comment 2:
At least least 4 years (e.g., 2015)given the expense of a variety of cage size and housing requirements that are being required at a time of great financial difficulty for research institutions.

218 04/19/2011 at 06:01:25 PM Self Johns Hopkins University Baltimore Maryland Comment 1:
I am an NIH-funded behavioral researcher and I am concerned by several aspects of the new Guide for the Care and Use of Laboratory Animals (new Guide) that I see as compromising scientific research with little if any demonstrated benefit for laboratory animal welfare. My concerns are that a) the new Guide contains recommendations that will, in effect, function like regulations, rather than guidelines for the care and use of research animals, b) the arecommendations are based on little scientific evidence in some cases, and c) the additional provisions will have a significant ecomomic impact on PHS-assured institutions. For these reasons, I believe the 1996 Guide should remain PHS policy and that the new Guide be used as a reference document. If the OLAW decides to adopt the new Guide as PHS policy, it should extend the unrealistic deadline from 2012. I believe 4-5 years would be necessary to full phase in the changes.

Of significant concern to me are the increased cost and regulatory and paperwork burden, in terms of justifications, requests for exception, and additional recordkeeping that will occur if the new Guide is adopted. Much of this will result from recommendations that lack empirical evidence of enhanced laboratory animal welfare. Of particular concern are a) Housing - detailed specifications for cage sizing and recommended use of solid bottom cages particularly for rats and mice is based on weak to nonexistent evidence. Required social housing for all species does not recognize practical constraints on institutions; (b) IACUC responsibilities – new requirements for post-approval monitoring and formal review of "unexpected outcomes" will require additional staffing and recordkeeping; (c) Surgery -- the caution against multiple major survival surgical procedures not only increases costs because of the increase in number of animals required, but also interferes with the scientific integrity of the study by not allowing the use of within-subject and single subject designs that are particularly powerful for behavioral research; (d) Food/fluid regulation – a new requirement to keep written records of both daily food and fluid consumption for animals under either restriction precludes the use of commonly used automatic watering devices, even when water is not restricted. Further, the recommendation that "a highly preferred food or fluid be used as positive reinforcement, instead of restriction" for "conditioned-response research protocols" is made despite information provided in the cited papers that such strategies do not work well to train behaviors – one of many examples of guidance that is inappropriate, both scientifically and for ensuring appropriate use of laboratory animals; (e) Use of Non-Pharmaceutical Grade Chemicals and Other Substances – this new policy is based on false premises. For example, not only do very few commercially available preparations exist that are suitable as tools for experimental research but they are also subject to formulation errors. Also, in behavioral research with drugs, including studies such as those I conduct, the commercially available preparations would need to be altered (diluted to particular dose concentrations), increasing rather than decreasing the margin of error.

I concur with the National Association for Biomedical Research (NABR) that the new Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB). Therefore, an opportunity for comment in greater detail from the research community on the substance of the new Guide and its financial consequences is necessary before a decision on the adoption of the new Guide as PHS Policy is made and an implementation strategy instituted.


Comment 2:
In my comments above I noted taht I think 2012 is unrealistic to fully implement the extensive set of recommendations listed in the new Guide.

219 04/19/2011 at 06:50:05 PM Self     Comment 1:
I completely support the content of the draft letter that you have or will soon receive from NABR. I find the 2010 Guide to be detrimental to science, biomedical research and the nation's commitment to improving the health and well-being of its citizens and the citizens of the world. Although I cannot materially improve upon the excellent points made in the NABR letter, I would like to add one observation. Whereas the OLAW FAQ notes that deviations from recommended cage requirements be documented and based upon scientific or veterinary data, no such condition was applied to developing these cage recommendations in the first place.


220 04/19/2011 at 06:59:45 PM Self   Baltimore, MD Comment 1:
Do not adopt. Retain the 1996 Guide.

The revised 2011 Guide is nearly twice as long as the 1996 version, and contains a great deal of new policy that promises to significantly increase: (a) the expense of research, (b) the paperwork burden on researchers, and (c) and the authority of local IACUCs to restrict already peer-reviewed research. And while some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food & liquid restriction).


Comment 2:
Do not adopt. Retain the 1996 Guide. If necessary, I recommend at least 4 years (i.e., 2015) for transition to the new Guide.

221 04/19/2011 at 07:07:35 PM Self     Comment 1:
Do not adopt these changes!!! No data is included that bigger cages are better or that pharmaceutical grade drugs give a better outcome. In the absence of this information- the proposed changes are simply 'thought experiments' that would significantly increase the administrative and financial burden on investigators, and restrict their ability to address valid experimental questions without any significant gain in animal welfare, experimental outcomes, or scientific knowledge.

Animals used for research are already closely watched and all protocols are already evaluated by expert panels to ensure animal safety. The system is working- it does not need to be changed.


Comment 2:
Do not approve- but if so- implementation must be as long as possible- minimum of 4 years.

222 04/19/2011 at 08:05:31 PM Organization LSUHSC School of Medicine New Orleans, LA Comment 1:
The whole scale adoption of the "Guide to the Care and Use of Laboratory Research" is an Extremely Bad idea for the future of medical research. The Guide's regulations are burdensome without benefit to animal welfare or science. Just a couple of specific points include: 1) there is no evidence that using pharmaceutical grade drugs would improve animal welfare or science; 2) commercial pharmaceutical grade formulations make careful pharmacological research difficult as these are single concentration formulations, which makes manipulating dose and vehicle comparisons difficult while at the same time maintaining pharmaceutical grade standard. Only pharmacuerical companies will benefit from these "Guide" restrictions.


223 04/20/2011 at 03:16:37 AM Self     Comment 1:
I have only just been notified that a new Guide is available. I cannot comment on it in a few days. I think that a comprehensive synopsis of changes needs to be provided to all current NIH grant recipients who work with animals and an appropriate time available for comment prior to adoption of such a document.


224 04/20/2011 at 07:50:34 AM Self     Comment 1:
1. On p. 83, 2 L of water for 1 adult X. laevis (especially females in production) is generally insufficient for routine housing; the traditional standard is actually 1 gallon (3.8L). We kept thousands of frogs and unless your filtration and water turnover systems, including organic skimming are on "operational steroids" or over-built, commercially sold housing systems at this density will lead to stress, disease (e. g. atypical Mycobacterium), and increased mortality. This is the standard that people who sell the equipment list to tout its virtues (because other designs can pack higher densities), but it is insufficient as a routine, especially when high growth rates and colony production are the goal, which is usually the case.

2. p 84. Use of latex gloves is toxic to larvae... If you read the 2 publications from that period, my recollection is that you will find that in addition to latex, nitrile and some batches of vinyl are also toxic! Wiping or rinsing before use in water, especially if talc or starch are present are best practices.

3. p 84-85. I can attest that live food should be avoided except where necessary (e. g. only food an animal will eat, and then only until one can get it on a complete artificial diet, if possible) because live commercial source food carried multiple atypical mycobacterium by PCR (16s and heat shock protein genes, etc.)and this in turn led to diseased frogs with considerably higher morbidity and mortality. Live prey should be considered at high risk of spreading disease, and some note of caution should be included here. You mention the health of the prey, but the Mycobacterium was a likely commensal, and prey can look healthy even when diseased. This is well known from fish culture and for other exotic species as well.


225 04/20/2011 at 08:47:15 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

226 04/20/2011 at 09:11:08 AM Organization Winston Salem State University Winston Salem NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

227 04/20/2011 at 09:14:53 AM Organization Wake Forest University School of Medicine Winston-Salem, North Carolina Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

228 04/20/2011 at 09:16:28 AM Organization Wake Forest Univeristy School of Medicine Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

229 04/20/2011 at 09:33:49 AM Self     Comment 1:
1)there is no evidence that using pharmaceutical grade drugs would improve animal welfare or science; 2) commercial pharmaceutical grade formulations make careful pharmacological research difficult as these are single concentration formulations, which makes manipulating dose and vehicle comparisons difficult while at the same time maintaining pharmaceutical grade standard 3) The regulation is burdensome without benefit to animal welfare or science.


230 04/20/2011 at 09:39:56 AM Organization Wake Forest University Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Data should drive decisions! Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

231 04/20/2011 at 09:46:04 AM Organization Winston Salem State University Biomedical Research Infrastructure Center Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

232 04/20/2011 at 09:50:10 AM Organization Wake Forest University School of Medicine Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

233 04/20/2011 at 09:59:28 AM Self     Comment 1:
I appreciate the focus of the new Guide remaining on performance standards rather than engineering standards. Having said that, there are a couple of items which appear to apply engineering standards in a manor which will have a signficant economic impact on the animal care program at the institution I am employed at. Specifically, the implied requirement to eliminate mouse harem breeding will significantly impact the requirement for ventilated mouse caging as well as impact the per diems needed to accomplish the aims of existing NIH grants since we charge for daily animal care by the mouse cage, not the individual mouse. Both of these items represent a signficant cost to our animal care program. We currently have 20,000 mouse cages, approximately half of which are breeding colony cages. The new Guide would double the number of cages needed for breeding colonies, representing an additional 71 ventilated racks of 140 cages each. The cost of this caging is currently $2.5 million for the 71 racks. The animal care budget of our existing NIH grant utilizing mouse breeding colonies would need approximately 2.6 million annually for the remainder period of the grant (10,000 cages x 0.72/cage x 365 days/yr) The estimated total direct economic impact at our institution would therefore be anywhere from $5.1M to $10.3M depending on the duration left on the grants. While this is a staggering amount when multiplied by the number of institutions that may be impacted, if there was scientific evidence to support this change, I would not object to the expense in the long run. HOWEVER, since there is NOT scientific evidence to support this change in mouse breeding cage space, I am not in favor of this guideline revision due to the significant negative economic impact it will have. Finally, it would appear that IACUC would no longer be able to approved programmatic exceptions to the Guide, but rather have to do that on an individual protocol basis. This too would appear to enhance the regulatory burden on the IACUC and decrease IACUC efficiency without benefit to the overall animal care and use program. I hope you will consider these two items and reword the 8th Guide document to relieve the economic and regulatory burden posed by this new edition when it would not enhance the animal care program in my professional opinion.


Comment 2:
Due to the economic impact of the new Guide as it applies to rodent breeding cage density, it is not feasible to obtain the funding or the caging in time to meet the March 2012 timeframe of implementation.

234 04/20/2011 at 10:04:47 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

235 04/20/2011 at 10:40:04 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new policy. Compliance with these new policy statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent.

The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare.

Again, the only way to ensure that these changes do enhance animal welfare, which should be the goal for all researchers, is to examine relevant data. In situations for which there is no relevant data, it is inappropriate to propose fixed policy.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

236 04/20/2011 at 10:46:15 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

237 04/20/2011 at 11:02:40 AM Self     Comment 1:
NIH should not adopt the new guidebook. The 1996 version is adequate to insure animal well being. Local IACUC regulations can mandate to specific policies to investigators with inuput from complete IACUC committees.


Comment 2:
Semiannual facilities inspections are appropriate.

238 04/20/2011 at 11:13:26 AM Self     Comment 1:
No, this should not be adopted.


Comment 2:
No, this is an unnecessary burden.

239 04/20/2011 at 11:13:52 AM Self University of Maryland School of Medicine Baltimore, MD Comment 1:
No


Comment 2:
March, 2015 or later for the collection of relevant data. Data should guide policy decisions.

240 04/20/2011 at 11:18:34 AM Self     Comment 1:
I OPPOSE the adoption of the 8th Edition of the Guide. The new specifications DO NOT represent an improvement on laboratory animal condition housing, but WILL cause an enormous MIS-SPENDING of now limited resources. I personally talked to several animal facility Veterinarians, and they all strongly oppose the directives including in this guide. The costs of implementation will be gigantic, and the benefits in terms of animal welfare will be ZERO.


Comment 2:
March 31, 2012 is too soon for an evaluation. Evaluations should be based on data, which may take some time to be collected.

241 04/20/2011 at 11:22:53 AM Self     Comment 1:
I believe OLAW should retain 1996 Guide as PHS Policy. My general concerns about the new edition include increased expense (e.g., new cage sizes for rodent breeding; larger cages for newly mandated social housing), increased paperwork burden (For example, all deviations from "should" statements contained in the new Guide will need to be in an approved protocol), and the increased power of local IACUCs to restrict already peer-reviewed research. Futhermore, I am specifically concerned about the constraints on multiple procedures in animals, constraints on multiple surgeries (not just multiple major survival surgeries), increased constraints governing food- or fluid-restriction, and poorly conceived instruction dictating the use of "chemicals and other substances" in laboratory animals.


Comment 2:
I recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements that are being required at a time of great financial difficulty for research institutions.

242 04/20/2011 at 11:24:15 AM Self     Comment 1:
The new guide (Eighth edition) should NOT be approved. It contains instances of over-regulation that will impede reasonable research. For example, stipulations regarding the use of pharmaceutical grade drugs in all cases are unworkable, burdensome in its requirements for approval of use of "non-pharmaceutical" drugs, and will end up significantly impeding research. Many changes, though well-intentioned, are very poorly thought out as to their consequences.


Comment 2:
This seems to be, in accord with a number of other changes proposed for the Guide, unnecessarily burdensome.

243 04/20/2011 at 11:24:25 AM Organization The Mount Sinai School of Medicine New York, NY Comment 1:
No. The NIH should abide by the recommendations of the working group that reviewed the prior public comment request and concluded that the 1996 Guide should not be revised with respect to policies and procedures.


Comment 2:
Same as above

244 04/20/2011 at 11:25:22 AM Self     Comment 1:
I am writing to object to the new guidelines. They are not necessary and will inject more hurdles into the job of medical research. The net result of these changes will be to prevent life saving treatments from being developed. The existing guidelines are quite effective in insuring that animal cruelty does not occur. Untold millions of human beings will suffer if medical research is further impeded.


245 04/20/2011 at 11:26:51 AM Self     Comment 1:
NO The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

246 04/20/2011 at 11:27:29 AM Self     Comment 1:
I strongly advocate NOT adopting the 8th edition.

It creates mischief that will actually HARM the care and use of laboratory animals.

The new guide is not an "update" of the 1996 Guide, but is much longer and contains a great deal of new "policy", most of which is ill-founded, illogical, very expensive, and yet has no support from scientific data that would justify such changes. Moreover, the 2011 Guide will dramatically increase paperwork without any benefit to animal subjects or to the underlying research that may impact on human health. This flies in the face of general efforts to reduce bureaucratic overhead.

In light of the lack of scientific basis for the new regulations, one wonders about the motivation for them and where scientific and veterinary input was during their creation.


Comment 2:
No, there needs to be relevant data collected to guide policy decisions. OLAW should require institutional compliance with the new Guide no sooner than 2015.

247 04/20/2011 at 11:29:13 AM Self     Comment 1:
NO it should not adopt this edition as a basis for evaluation of institutional programs.The new guide is not an "update" as originally proposed but contains a great deal of new "policy." Compliance with these new "policy" statements will greatly increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). Moreover, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden. Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies increase infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures. THE END RESULT WOULD BE TO SEVERELY IMPEDE ADVANCES MADE BY BASIC RESEARCH WITH NO GAIN IN ANIMAL WELFARE.


248 04/20/2011 at 11:32:38 AM Self     Comment 1:
No, do not adopt this edition. The prior comment period consensus was that no revision to the Guide was warranted. This current revision is a great example of bureaucratic mission creep and should be used throughout the government's various entities as an example of how not to interact with the interest groups affected by the agency. How about waiting until we request a revision to the Guide or at least agree that one is needed before launching such an unnecessary effort.


Comment 2:
No, see above.

249 04/20/2011 at 11:34:12 AM Self Tufts University Medford, Massachusetts Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements will increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). As a researcher I depend on newly developed drugs with therapeutic potential. These substances are investigational drugs. They need to be studied before being developed further for clinical use in human and veterinary medicine. However, the scientific data justifying the expense changes for using larger cages and pharmaceutical grade drugs are non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real, proven enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction (in spite of data to the contrary), naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

250 04/20/2011 at 11:48:08 AM Self     Comment 1:
The revised version of the Guide should NOT be approved in its present form. The new Guide, supposedly an update, is now twice as long and contains a great deal of new, highly-biased "policy." Compliance with these new mandates will do little for animal welfare but at the same time it will increase the expense to institutions (e.g., cage size) and the expense to investigators (e.g., drugs). Even worse, there are NO data to support any of these unfunded mandates. Adherence to the proposed Guide will unduly increase the paperwork burden since any deviations from "should" statements require justification ad infinitum. Moreover, the new "Guide" policies increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures (thus INCREASING the number of animals in an experiment), constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures).


Comment 2:
Be serious....OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data on the validity of the plethora of regulations. It is the data that should guide policy decisions, not highly-biased anti-vivisection extremists.

251 04/20/2011 at 11:52:07 AM Self     Comment 1:
No. The 8th addition should not be adopted as it includes substantial and expensive changes that are not supported by data that such changes will improve either animal husbandry or research quality.


Comment 2:
This time frame seems much too short given the number of issues that need to addressed with real data.

252 04/20/2011 at 12:04:15 PM Self     Comment 1:
Quite simply, no. NIH should not adopt the 8th edition of the Guide. Many of the changes (and there are extensive changes rather than simply an update) are new directives that are based on hearsay rather than objective data from peer-reviewed publications. This extends a problem already present, but to a lesser degree, with the previous edition.


Comment 2:
One cannot base reviews on a poorly generated document that lacks scientific rigor. Recommend that we do not implement the semiannual review/evaluation based on guidelines promulgated in the 8th edition.

253 04/20/2011 at 12:04:36 PM Self University of Arkansas for Medical Sciences Little Rock, AR Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements are likely to increase the expense to institutions, particularly in implementing new cage size limits; as well as expense to investigators to pay for increased cages. Investigators will also need to purchase drugs at increased costs to meet the new regulations. In neither case is there any scientific data justifying these new regulations. Without data showing that current guidelines are inadequate, there is little basis for changing them. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data to justify the new regulations. Without data showing that current guidelines are inadequate, the new regulations are questionable at best.

254 04/20/2011 at 12:11:57 PM Self     Comment 1:
No, this should not be adopted.


Comment 2:
No, more time is needed before requiring compliance to insure sufficient experience with new guidelines to understand problems that will be introduced that will unnecessarily impede progress in biomedical research.

255 04/20/2011 at 12:14:46 PM Self     Comment 1:
NO - do not adopt this guide

The new guide was originally supposed to be an "update" of the 1996 Guide. However, the new guide is twice as long and contains a great deal of new "policy." The key problem is a lack of any scientific rationale for the changes. Compliance with this immensely burdensome approach will increase the expense to taxpayers, require large increases in paperwork burden, infringe on scientific based decisions, and slow progress in biomedical discovery and treatment development. At the end of the day, this guide will provide NO REAL IMPROVEMENT in animal welfare, but impede science and medicine.


Comment 2:
This new Guide should be tabled and only data driven approaches should be utilized for policy decisions.

256 04/20/2011 at 12:14:57 PM Self     Comment 1:
I do NOT think the New 2011 Guide should be adopted in its present form.

I have listed my concerns below:

1) The use of non pharmaceutical grade chemicals (page 31). What had previously been restricted to anesthetic and analgesic agents, because of the language, could now theoretically be applied to ALL chemicals we administer to our subjects. This will dramatically increase the cost of resaerch without any scietific justification for this new requirement.

2) Food and water restriction and the level of monitoring of these animals that will be required (page 30). No distinction appears to be made between the monitoring required regardless of whether the subjects are food restricted OR fluid restricted. In other words, the language reads that daily food and water consumption and hydration must be monitored for both types of restrictions. Again - what is the scientific justification for these chagnes and if implemented this new requirement will greatly increase the record keeping requirements.

3) Cage sizes - particularly for breeding animals. Basically, there is room only for a mouse dam and litter, no harem breeding. For rats, I do not believe that many single cages are large enough for the dam and pups (ventilated rack cages are definitely not large enough), it will require oversized cages. These issues bring up concerns about additional costs and crowding in our already overcrowded facilities.

4) While many of the changes are listed as "should"s versus "must"s there is also a great deal of concern about OLAW's distinction between the two with several people saying that while the "Guide" makes the distinction OLAW does not. I also feel that while AALAC and many IACUC committees will take a reasonable approach regarding "must"s and "shold"s in the new Guide, I am concerned that outside animal activist groups will simply use these changes as addditonal "weapons" to impede research - perhaps by filing lawsuits to "enforce" these new regulations as THEY (or the courts) interpret them.


257 04/20/2011 at 12:26:06 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

258 04/20/2011 at 12:29:23 PM Self     Comment 1:
I urge the NIH to NOT adopt the eight edition of the Guide. We will not be able to comply with the requirement to use only pharmaceutical grade drugs in rodent studies. There are no pharmaceutical grade formulations available for several of the drugs we routinely use for our studies, including cocaine. For other drugs, the pharmaceutical grade formulations are significantly more expensive. These additional costs were not budgeted into our grants and will result in a drastic decrease in our research productivity. Ultimately, this may lead to the loss of research funding and jobs, which will negatively impact human health, science, and the US economy.


Comment 2:
I urge the NIH to NOT adopt the eight edition of the Guide. We will not be able to comply with the requirement to use only pharmaceutical grade drugs in rodent studies. There are no pharmaceutical grade formulations available for several of the drugs we routinely use for our studies, including cocaine. For other drugs, the pharmaceutical grade formulations are significantly more expensive. These additional costs were not budgeted into our grants and will result in a drastic decrease in our research productivity. Ultimately, this may lead to the loss of research funding and jobs, which will negatively impact human health, science, and the US economy.

259 04/20/2011 at 12:30:59 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

260 04/20/2011 at 12:45:29 PM Organization Univeristy of California, San Diego La Jolla, CA Comment 1:
The 8th edition of the guide is flawed, and should not be adopted for a number of reasons. I will list the primary three: The first is a substantial increase in research costs due to the housing requirement changes, that have no scientific backing in terms of improving animal health over the current housing recommendations. The second is even more important, the requirement to use pharmaceutical grade drugs in research. Not only do very few commercially available preparations exist that are suitable as tools for experimental research, but also, commercial solutions themselves are subject to formulation errors, as evidenced by recent recalls. Even with solutions that may be useful for a particular project, the need to conduct dose-effect evaluations inevitably means the commercial solution would need to be diluted in the laboratory to accomplish this purpose. Third: by changing the already very rigourous recommendations of the guide yet again, the paperwork/implementation/regulatory burden that is created is astronomical. I am an IACUC member of my institution and the added burden of complying with the new recommendations (some of which are written in very vague or downright illogical manners) will be extensive on an already "tipped to the breaking point" group of scientists and administrators. Scientists already have to spend more and more time writing grants becuase of the reduced payline, more and more time on regulatory paperwork and administrative duties required by funding and other agencies, the time alloted to research and scientific discovery is shrinking continuously. The guide's consequences of reducing time devoted to research for no clearly defined benefit to the quality of research will only undermine further health care research, and does not support the NIH mission.


Comment 2:
Why, in a time of reduced funding to NIH are we requiring yet more time wasted from already incredibily burdened NIH and other institutional adminstrators and scientists? The amount of time spent already on protocol review, laboratory and vivarium inspections is more than enough to ensure proper animal care and handling in research. Animals in laboratories are the MOST well cared for animals on the planet. At this time, adding yet more contraints and regulations to research in the form of changing animal research guidlelines with no clear reason to do so at a time of 8% funding paylines does not seem logical or helpful. These changes will require NIH funded scientists to spend yet more time NOT on science but on paperwork, committees, and administrative reviews. This is, in my opinion, not the time for NIH to be focusing on poorly considered changes to animal regulations, but instead on things more important to the core NIH mission, which is conducting and supporting the best scientific research for improving human health.

261 04/20/2011 at 12:50:29 PM Self University of California Irvine California Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

262 04/20/2011 at 12:52:42 PM Self     Comment 1:
My answer is NO it should not adopt this edition. The edition has a number of changes that will impair medical research and should be strongly opposed by all humanitarians.


263 04/20/2011 at 01:02:52 PM Self     Comment 1:
As a board-certified laboratory animal veterinarian with 30 years of experience, and as an AAALAC Council member Emeritus, I strongly endorse adoption of the eighth edition of the Guide. The new edition provides valuable new information, including material on aquatic species, and forms a framework for eventual harmonization of animal care practices world-wide. In my view, this new edition is five years overdue. Failure to adopt it would mean that facilities that care for and use research animals would remain without a useful guiding document for the foreseeable future.


Comment 2:
As an ACLAM diplomate and former member of the AAALAC International Council on Accreditation, I support the proposed implementation time frame of approximately one year. There are no new elements of the Guide that could not be addressed by institutions within that period.

264 04/20/2011 at 01:03:46 PM Organization American Society for Pharmacology & Experimental Therapeutics Bethesda, MD Comment 1:
The Association for Pharmacology and Experimental Therapeutics (ASPET) comprises 4800 members who are experts in research across a wide range of specialties, as indicated by the names of its divisions: Behavioral Pharmacology, Cardiovascular Pharmacology, Drug Discovery & Development Drug Metabolism, Molecular Pharmacology, Neuropharmacology, Toxicology, and Translational & Clinical Pharmacology.

ASPET urges OLAW not to adopt the 2011 edition of the Guide. Its deviation from the 1996 Guide will result in a significant increase in regulatory and paperwork burden and expense without benefit to animal welfare. ASPET supports the comments of NABR that were submitted to Francis Collins, Director of NIH. Our comments will focus on the newly added section "Use of Non-Pharmaceutical Grade Chemicals [NPC] and Other Substances," which adds new policy to the Guide that is unwarranted with respect to animal welfare or good research practice. Albeit well intended, this policy is not well informed regarding the conduct of research that uses drugs in laboratory animals.

One problem with the new guidance on NPC is that the term "pharmaceutical grade" is not defined, nor does an accepted definition exist. An indication of its intended meaning is Guide citation of USDA/APHIS Policy 3, which covers "sedatives, analgesics, or anesthetics" used to prevent pain/distress with regulated species. Its use of "non-pharmaceutical grade" refers to medications not prepared for clinical use. The Guide extends Policy 3 terminology to all vertebrates and all chemicals used in research. The implication is that all solutions prepared by a researcher are considered of inferior quality and that clinical solutions are ideal for research, neither of which is accurate. Specifically, ASPET notes the following with respect to the four sentences on NPC in the Guide: (1) "The use of pharmaceutical grade chemicals. . .ensures that toxic or unwanted side effects are not introduced into studies. . . ." The use of commercially prepared solutions does not ensure this. There are many examples of commercial solutions being recalled. Mass manufacture of pharmaceutical grade drugs amplifies any error.

(2) "They should therefore be used, when available, for all animal-related procedures. . ." The assertion that clinical formulations are superior for all-animal-related procedures is neither logical nor supported by scientific evidence. Laboratory-prepared formulations have been the norm in research for the last century. There is no evidence that research or animal welfare would be improved by changing this research practice. The way in which drugs are formulated for clinical use make them poor choices for research. For example, dose manipulations are essential to research. Unlike clinical use, volume of drug delivery needs to be held constant. The single concentrations of solutions sold commercially inevitably need to be diluted to manipulate dose. The assumed benefit of using a commercial solution is lost. Another element of good research is comparison of the effects of the drug with that of vehicle alone. Vehicles of commercial solutions cannot easily be duplicated.

(3) "The use of [NPCs] should be described and justified in the animal use protocol and be approved by the IACUC. . . for example, the use of [NPC] may be necessary to meet the goals of a project or when a veterinary or human pharmaceutical-grade product is unavailable." The wording implies the need for an NPC is unusual. In reality, it is the rule. The vast majority of animal research involves compounds that are not used clinically. New chemical entities are keys to advances in science and public health. Collaborations with academic, government, or industry chemists are common; many high purity compounds are available from highly regarded commercial sources. Drug supply programs at NIH make controlled substances and other compounds not formulated for use in humans available to researchers without cost, as do biotechnical and pharmaceutical firms. To require that each use of an "NPC" be justified in writing and reviewed and approved by an IACUC places an unwarranted paperwork burden on researchers and on the IACUC.

(4) "Consideration should be given to the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation, compatibility, and pharmacokinetics of the chemical or substance to be administered, as well as animal welfare and scientific issues relating to its use (NIH 2008)." These considerations are applicable to veterinary care, but are of more variable relevance to research. A part of each research project that uses chemical compounds necessarily involves determining details of their use that will assure the meaningful characterization of the effects of the compound. ASPET suggests that requiring these to be spelled out in advance, and reviewed and approved by the IACUC singles out pharmacology research for micromanagement--a function that has not been the traditional goal or value of the Guide. Note also that the citation is to an intramural NIH guideline, which defines "pharmaceutical grade" differently than does USDA/APHIS Policy 3.

In summary, the newly added Guide requirement to use drugs formulated for clinical use in research animals is not realistic. For the few situations in which such a drug might be available, the practical needs of research make them unsuitable, and the cost, compared to one suited for laboratory can be significant (e.g., up to 10-fold). To require NIH's drug supply programs to substitute clinical-use solutions for all those it currently provides via its drug supply programs would be an expense that does not justify use of scarce research dollars. Should OLAW adopt the 2011 Guide, ASPET urges that it consult NIH Institute Directors regarding the wisdom of including the NPC section as PHS Policy.


Comment 2:
ASPET concurs with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, setting a date by which PHS-Assured institutions must comply with the new Guide prior to an OMB analysis of its financial impact on those institutions and NIH itself is premature.

265 04/20/2011 at 01:29:20 PM Self     Comment 1:
NO. The new guide contains a great deal of new "policy", in which compliance with these new "policy" statements may increase the expense to institutions and investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden. Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare.


Comment 2:
OLAW should require institutional compliance with the new Guide at a much later date to allow for the collection of relevant data. It is the data that should guide policy decisions.

266 04/20/2011 at 01:33:39 PM Self   Shreveport, LA Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

267 04/20/2011 at 01:35:44 PM Self     Comment 1:
I oppose the adoption of the new guide since it places significant burdens on scientists with little additional protection for the animals.


Comment 2:
I believe you should allow more time for evaluation before fully implementing the new guide.

268 04/20/2011 at 01:39:42 PM Organization UT Southwestern Medical Center Dallas, TX Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

269 04/20/2011 at 01:41:13 PM Self     Comment 1:
No


Comment 2:
No

270 04/20/2011 at 01:41:24 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

271 04/20/2011 at 01:49:52 PM Self Center for neurobiology and Behavior, U. of Pennsylvania Phila., PA Comment 1:
No, the NIH should not adopt this guide.


272 04/20/2011 at 02:11:11 PM Self Keck School of Medicine of University of Southern California Los Angeles, CA Comment 1:
No, the NIH should not adopt the new guidelines.


Comment 2:
No, the evaluation program is redundant, expensive and will impede research. The administrative load the the NIH is proposing to impose will utilize precious resources that would be directed to paper work and not to improvement of care of animals used in scientific research. It would do exactly the opposite of what the NIH wishes to accomplish. An annual evaluation schedule would provide outstanding monitoring.

273 04/20/2011 at 02:11:52 PM Self Emory University Atlanta, GA Comment 1:
NO.

The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy" that will restrict research and increase the expense to researchers and institutions WITHOUT ANY CLEAR BENEFIT TO ANIMAL WELFARE. These suggested changes have been made in the COMPLETE ABSENCE OF SCIENTIFIC DATA supporting them.


Comment 2:
NO.

OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

274 04/20/2011 at 02:18:49 PM Self     Comment 1:
The proposed changes will impose unnecessary overregulation of experimental details. Investigators need to design each experiment to optimize animal safety and scientific value, and excessive regulation interferes with these decisions.


Comment 2:
I recommend that the impositions of new policies be deferred to May, 2015

275 04/20/2011 at 02:37:20 PM Self     Comment 1:
NO


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

276 04/20/2011 at 02:40:53 PM Organization The University of Toledo Toledo, OH Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require a large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies will cause increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.

Collectively, these new policies attempt to install unnecessary restrictions and protocol in scientific animal research and attempt to govern scientific inquiry with ineffective and redundant bureaucracy.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions. Until properly evaluated, these new policies may slow existing research and introduce unneeded confusion to animal protocol.

277 04/20/2011 at 02:50:05 PM Self     Comment 1:
The major shortcoming of the new Guide is the lack of empirical data to justify the additional expenses that will be incurred by principle investigators (PIs) and their institutions to accommodate the proposed new changes. The chapter on veterinary care (Chapter 4 in the proposed new Guide) is no exception. In general, the proposed new changes clearly mandate increased consultation and oversight of veterinarians, beyond what the 1996 Guide required. In and of itself, increased veterinarian oversight of all aspects of care and use of animals may, indeed, be a good thing. However, the questions that are not addressed are why, and at what cost? Would hiring more veterinarians for consultation and supervision significantly increase animal care at institutions that are following the 1996 Guide? Is it worth the additional costs for PIs and institutions to employ this extra supervision, if they are experiencing no problems and if their IACUCs are satisfied with the present care and use of animals at their institution's facilities? Perhaps some institutions can afford this, but there are many others that are on the brink of closing their animal facilities because of the escalating costs, and the educational, societal, and economic impact these closings could have may far outweigh whatever unspecified shortcomings the proposed new guidelines have been created to address.

The proposed new Guide (Ch 2, page 14) makes the attending veterinarian (AV) responsible for all animal care and welfare. If an IACUC interprets this strictly, they may decide to mandate the hiring of a full-time AV, which may be prohibitively costly for some institutions. The proposed new Guide also puts more emphasis on the role of the AV in reviewing the health status of animals from non-commercial sources (Ch 4, page 108), selecting anesthetics and analgesics (Ch 4, pages 116 and 121), use of neuromuscular drugs (Ch 4, pages 122-123), and standard methods of euthanasia (Ch 4, pages 124).

Although few would object to having more AV involvement in animal care and use, there are no data to indicate that these changes are necessary, nor were any cost/benefit analyses for mandating such changes cited. Is the current AV oversight role insufficient for appropriate animal care? Haven't the trained animal care technicians, PIs, and the institutional IACUCs, who have been responsible for much of this monitoring of animal care during the past 30 years, been doing an adequate job?

The cost burden of increasing the involvement of an AV may be too high for some institutions to continue to conduct animal research, and it seems grossly unfair to impose this on institutions whose animal care programs have been functioning extremely well under the present guidelines, when there is no evidence to indicate that many of the changes in the new proposed Guide is needed at all, let alone if they will result in a significant improvement to the welfare of the animals at these institutions.


Comment 2:
First, I do not see a need for this proposednew Guide. Is there a report or data that suggests that the existing Guide is not adequately protecting the welfare of laboratory animals? Is the added costs and burdens of the proposed new Guide resolving some problem of which many of us have not been notified? Adopting the proposed new Guide in time for inspections by March 31, 2012 is an excellent example of how out of touch the beauracracy is concerning the issues researchers using animals are facing. It is unreasonable to impose these measures in such a short time frame. It is especially onerous considering that most of the new stipulations are unncessary, restrictive, and costly. At the very least, a thorough cost/benefit analysis for implementing the new Guide should be mandated BEFORE any suggestion of an adoption date be forwarded.

278 04/20/2011 at 03:08:26 PM Organization Wake Forest University School of Medicine Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions

279 04/20/2011 at 03:16:29 PM Organization Wake Forest University Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

280 04/20/2011 at 03:17:37 PM Organization Winston salem state university winston salem, NC Comment 1:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions

281 04/20/2011 at 03:18:14 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). The scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

282 04/20/2011 at 03:23:57 PM Self     Comment 1:
No compelling need for any changes on current policy. So, I vote NO for changes.


283 04/20/2011 at 03:33:25 PM Self     Comment 1:
Response: NO. Many of the recommendations contained in the 2011 Guide are not based on scientific evidence, and could seriously impede progress in research that will benefit public health. Most recommendations will require significant costly alterations for institutions and investigators.

Examples of recommendations that have little scientific basis and could negatively impact research progress are as follows:

The recommendation for use of pharmaceutical-grade drugs: There is no evidence that pharmaceutical-grade drugs would improve animal welfare. Moreover, research could be impeded because commercially available pharmaceutical-grade formulations are often single concentrations that make it difficult or impossible to manipulate drug dose or to compare different vehicles. Moreover, pharmaceutical-grade drugs will increase the cost of pharmacological research by 500 to 1,000 times in some instances.

Recommendations for Constraints on multiple procedures in animals: It is often in the best interest of science to conduct longitudinal studies in animal subjects using repeated measures in an own control design. Some nonhuman primates live for more than 25 years, and repeated measures are often necessary to answer research questions. Repeated surgeries are often necessary to repair or prolong the life of surgically implanted experimental devices.

Recommendations for Paired housing for nonhuman primates: Despite the attractive "face validity" of paired housing and the opportunity for physical contact between pairs of nonhuman primates recommended in the 2011 Guide, this would place animals at risk for injury and death. Aggression in response to any surprise (a novel noise, person, pain, etc.) may lead the dominant member of the pair to attack/kill the weaker or more submissive cage mate. Studies that require implantation of any device such as an IV catheter to evaluate medication effectiveness could not be conducted.

Recommendations for Changes in cage size: There is no scientific justification for modifications in cage sizes and configurations specified in the 1996 edition of the Guide. The cost to institutions and to investigators would be astronomical!


Comment 2:
Response: Implementation of any changes to the 1996 Guide should be delayed for at least five years (March 2015) to allow NIH to gather scientific evidence to support or to refute the many problematic recommendations proposed in the 2011 Guide. The requirement for additional oversight will add to an already onerous regulatory burden that eventually will be unsustainable for many research institutions. The ultimate impact will be serious damage to this nation's preeminent leadership in health-related research.

The NIH must recognize that lobbying efforts by groups opposed to all research with animals, such as the Humane Society of America and the Physicians for Social Responsibility, are reflected in the proposed changes to the Guide. It would be most unfortunate if NIH standards for insuring animal welfare were primarily influenced by the well-funded political agenda of those organizations opposed to all research on animals, rather than humane concerns for animal welfare and commitment to advances in science.

284 04/20/2011 at 03:38:24 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.

This combination of decreasing support for research while at the same time making research more far expensive to conduct shows an astounding lack of foresight and is creating a major crisis for our country at a time when we need to be promoting innovation and making dollars go further.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

285 04/20/2011 at 03:43:50 PM Self     Comment 1:
No -- NIH should NOT adopt the 8th edition as the basis for evaluating institutions that receive PHS support.

The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data.

It is the DATA that should guide policy decisions.

286 04/20/2011 at 03:47:30 PM Self     Comment 1:
No


287 04/20/2011 at 03:48:12 PM Self Whitman College Walla Walla, WA Comment 1:
I support fully the comments and concerns put forth by NABR. They have done an outstanding job of evaluating the new edition, and raising substantive objections. There is no sound rationale for this expansion beyond creating more mid-level administrator positions. The current edition does an excellent job of ensuring responsible, humane treatment of animals in laboratory settings.


Comment 2:
There is no scientific data supporting the vast expansion of the proposed eighth edition of this guide, and as someone conducting research at a small liberal arts college, the added administrative burden will kill our ability to do effective research with our already limited amount of time, and interfere with our ability to train effectively the next generation of scientists in animal research. Somewhere, someone needs to decide what is enough and use reason to draw a line. I hope that the NIH is able to do so at this time. Please reject this new edition.

288 04/20/2011 at 03:54:05 PM Self Wake Forest University School of Medicine Winston Salem, NC Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

289 04/20/2011 at 03:55:20 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

290 04/20/2011 at 04:13:04 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

291 04/20/2011 at 04:16:47 PM Self     Comment 1:
No


292 04/20/2011 at 04:18:17 PM Organization Lycoming College Williamsport, PA Comment 1:
I am writing as the chair of the Animal Care and Use Committe, and as a small animal researcher at Lycoming College, a small, exclusivley undergraduate, private liberal arts and sciences college in northcentral Pennsylvania. I have grave concerns over the proposed changes to the GCULA. First, there is no justification provided as to why the GCULA needed updating: what problems with animal welfare are the proposed changes supposed to address? Second, there are no data provided indicating the the proposed changes will in fact improve animal welfare significantly. Third, and most ominously, the added burden on small institutions such as Lycoming College, in terms of time, space, and money, is significantly increased by the proposed GCULA changes. If the changes are passed, it may no longer be feasible to conduct publishable animal research or provide animal research training for undergraduates at small institutions such as Lycoming College. I share these concerns with other faculty at small undergraduate institutions through my service as a Counselor with the Faculty for Undergraduate Neuroscience. We believe the current (7th) version of the GCULA serves the animals, the students, the colleges, and the nation's biomedical research enterprise quite well. We also believe that any significant changes to the GCULA must be justified by scientific data, which are lacking in this proposal. Moreover, we believe that the impact of changes on the nation's education and research infrastructure must be studied and taken into consideration before any changes are enacted.


Comment 2:
The proposed requirement for semiannual program and facility evaluation represents a significant burden for small undergraduate colleges. Who will pay for this review, which goes above and beyond what our own IACUC already does? And what scientific benefits will come from forcing more frequent reviews and documentation? Many small colleges like my own already struggle to do their animal research training under their teaching budgets, not subsidized by large national-level grants that provide "overhead" to the administration to defray such bureaucratic expenses. Mandating annual reviews will result in fewer undergraduate colleges providing animal research training to their students. This would not be in the nation's best interests, or in the best interests of animal research itself. If such a requirement is instituted, at the very least, there must be some sort of mechanism for smaller institutions to do their reviews at a different interval from the large, nationally-funded ones. Otherwise, substantial damage to the training opportunities for undergraduates will be the result.

293 04/20/2011 at 04:22:08 PM Self     Comment 1:
There does not appear to be any rationale, supported by empirical evidence, for the need for a revised Guide. The revised Guide appears to have the force of a set of regulations with restrictions that can have a chilling effect on the use of animals in research and teaching. Furthermore, the substantial increased costs entailed in the Guide is likely to have the same effect on research with animals. Before the Guide is adopted there should be an opportunity for a thorough and meaningful review by agencies representing animal research and research scientists, such as the American Psychological Association, the Association for Psychological Science, and the National Association for Biological Research. Under the current deadline no such review is possible.


Comment 2:
For the reasons stated in Comment 1 concerning adoption of the revised Guide, there is no basis for implementing NIH's plan regarding facility evaluation that is based on that revised Guide.

294 04/20/2011 at 04:23:33 PM Self     Comment 1:
I'm not sure that the current guide is lacking in its recommendations for the care and use of animals in research. The current guide seems to be useful for oversight and assistance at my institution and imposing additional regulations not only presents additional hurdles to researchers but could potentially create additional loopholes. The current guide is a fairly concise narrative given the broad scope of research carried out under its ethical purview.


Comment 2:
I'm not sure this new edition couldn't be considered a supplementary/elective document.

295 04/20/2011 at 04:29:53 PM Organization Laboratory Animal Breeders Association Wilmington, Massachusetts Comment 1:
The Laboratory Animal Breeders Association recommends that OLAW not accept the 2011 Guide in its present form. We recognize the need for a guidance document for the US biomedical research community in order to set standards that take into consideration ethical responsibilities, animal welfare, and research concerns associated with the use of animals in research, teaching and testing. Such a document should leave room for professional judgment at an institutional level to apply performance standards in order to tailor practices and facilities to the needs of research animals. While the 2011 Guide acknowledges this principle, it sets forth, frequently as minimum standards, new engineering standards, new strong recommendations, and certain new prohibitions These standards, while similar to ETS 123, do not include the same caveats and hence, have more profound and costly unintended consequences. These stricter standards cannot be supported by peer-reviewed scientific studies. The level of specificity of guidance needs to be proportional to the robustness and specificity of the science supporting it. Such guidance should also still allow for the application of professional judgment and experience coupled with performance based measures applied at an institutional level using IACUC oversight to implement animal welfare based outcomes. In the case of the 2011 Guide, for example, the new cage space allocations for a mother with litter for rats and mice do not appear to be supported by robust science; yet, they will have an extreme negative impact in terms of costs, adherence to the principles of the three Rs, and depending upon how compliance is achieved, on animal welfare. If applied as a minimum standard, as suggested, they will have an extreme negative impact in terms of capital and operating costs, without commensurate benefit to the welfare of the animals. In some cases, not only is new guidance not supported by scientific evidence, it is contradictory to other guidance such as is the case in requiring that the floor space occupied by enrichment items be subtracted from the total floor area. Similarly, tightening of relative humidity ranges that is worded as a strong recommendation is not supported by scientific data yet will have a substantial operational and equipment cost impact on most facilities. In this case the strength of the recommendation is disproportionate to any theoretical positive animal welfare benefit. Clarification of the interpretation and application of this recommendation is not only needed but any strict application of this guidance should be justified at an institutional level based upon experience and professional judgment. Overall, we would recommend that OLAW gather more detailed information on issues associated with changes in the 2011 Guide before making a final decision. Based upon these concerns, an analysis of both the scientific justification for such additions and the financial impact of these additions should be undertaken especially if they are to be applied as minimum standards. Decisions on how the Guide will be used can then be made on a rational basis in proportion to the amount and strength of evidence supporting proposed changes in guidance.


Comment 2:
The Laboratory Animal Breeders Association agrees with OLAW that each institution should begin to make an assessment of areas of compliance and noncompliance with new guidance presented in the 2011 Guide. This evaluation should be completed by the deadline suggested. However, the evaluation should include, in addition to a timetable for compliance, a feasibility and economic impact statement for correcting areas of noncompliance. This is in keeping with our recommendation for a more robust analysis of new recommendations found within the 2011 Guide. Based upon this analysis, OLAW should decide if the Guide will be accepted as written and if so, should all recommendations be implemented; where significant economic impact is identified, should guidance be provided outlining reasonable and perhaps institution specific schedules for conformance or will certain recommendations require further scientific justification by an independent body such as the National Academy of Sciences perhaps using a group other than the Guide Committee assembled for this purpose. While animal welfare is an important component of biomedical research activities, recommendations for the care and use of laboratory animals need to be based on sufficient sound science and must consider the amount of resources that will be required to implement them. If such recommendations are limited or uncertain in their established ability for or level of improvement of animal welfare, if they are based principally on professional judgment, or if they do not consider all the variables that might impact their desired effect, they cannot be considered to be useful as universal guidance and certainly not be considered as minimum standards or strong recommendations. Moreover, they do not warrant wide spread application or the expenditure of disproportionate amounts of the ever decreasing resources available to the research community that will be required to implement them. The Laboratory Animal Breeders Association has calculated that at a minimum approximately $500 million in capital expenditures and $155 million dollars of increased operating expenses (not including amortization of capital expenses) will be required by its members to address some of the recommendations in the 2011 Guide. We feel that this level of expenditure when coupled with the estimates from the research community will merit more consideration of the strength of the scientific support for these recommendations before implementation should be considered.

296 04/20/2011 at 04:32:03 PM Self     Comment 1:
Please continue to use the 1996 Guide as the standard for laboratory animal care. Teh new guidelines will severely limit the abilities of Investigators, especilly new investigators to perform quality research.


Comment 2:
If the new Guide is implemented, please allow at least four years for complete compliance. This will allow research institutions time to purchase and set up new, costly caging and other requirements.

297 04/20/2011 at 04:32:25 PM Organization Medical College of Wisconsin Milwaukee, WI Comment 1:
The Medical College of Wisconsin (MCW) acknowledges the 8th edition of the Guide offers improved programmatic guidance in many respects, including expanded reliance upon peer-reviewed scientific literature as the basis for many recommendations. However, MCW has serious concerns about the potential impact of this document and cannot recommend its adoption by OLAW unless those concerns are addressed.

Although the Guide contains several new recommendations that likely would result in additional programmatic costs, of preeminent concern to this institution are the new recommendations for minimum animal space, particularly for breeding rodents. Strict implementation of the new space recommendations would result in significant new start-up and recurring costs to this institution and its federal grant recipients. While such costs might be warranted if there was sound evidence demonstrating improved scientific outcomes or enhanced animal welfare, the new space recommendations are not based on any scientific investigations nor any data indicating the 1996 recommendations are inadequate. As such, the costs to implement the recommendations would be incurred for no proven benefit to science or animals.

Like MCW, many academic institutions maintain large mouse breeding colonies, and we are confident many respondents will address concerns about the affects of the recommendations on investigations involving mice. However, MCW also maintains one of the largest academic research rat colonies in the world. We currently maintain more than 2,000 active breeding pairs and over 350 different inbred, transgenic, knockout, and consomic/congenic strains. These animals represent a unique, critically important resource for research conducted at MCW and around the country. Therefore, we chose to specifically illustrate the potential impact of the recommendations on this enterprise and the investigations it supports.

In recent years MCW has invested more than $4 million to purchase individually ventilated cages (IVC) specifically to accommodate our growing breeding colonies of both rats and mice using the space recommendations of the 7th edition of the Guide. Each rat IVC provides approximately 140 sq. in. floor space. Nearly all of our rat breeders are set up as continuously co-housed monogamous pairs, and litters are raised in the cage with both parents. Implementation of the new space recommendations for a female rat with litter (table 3.2, page 57) would preclude this practice because our caging would not be big enough for a monogamous breeding pair plus a litter. This would necessitate separating each breeding pair prior to parturition and only re-pairing the animals after the litter has been weaned. Because separating the breeders like this would not permit mating during the female rat's postpartum estrus, the number of litters produced by each female would be reduced by nearly 50% per year. Subsequently, we would have to significantly increase the number of breeding animals and cages in order to maintain the current breeding colony production. We estimate this would cost the institution between $340,000 and $680,000 just for purchase of additional IVC caging. Furthermore, additional animal holding rooms would need to be freed up to accommodate the added caging, which may not be feasible.

In addition to the cost to this institution for additional rat caging, the direct charges to grants for animal care also would increase markedly. Based on our current animal care costs/rates, the projected increase in the average daily census of rat cages needed to support the current level of research activity would translate to an additional $397,000 to $794,000 per year in animal care charges to investigators due to the change in housing density. And those charges would be compounded by the added personnel costs needed to separate and then re-pair breeders nearly 11,000 extra times per year. In the face of such increases in charges, especially in light of the current funding climate, investigators may be forced to cut back on or even abandon research projects involving rats, which would jeopardize the public investment already made in important projects.

Although we detail above the perceived impact on research involving rat resources, MCW anticipates a similar, albeit somewhat less dramatic, impact on projects involving mouse breeding programs.

We note the Guide does indicate that adjustments to the space recommendations may be reviewed and approved by the IACUC "based on performance indices related to animal well-being and research quality." However, from a practical perspective, the text on page 55 providing guidance on such indices illustrates several situations in which more space than that which is listed should be provided, but offers little in terms of situations in which less space would be acceptable. As such, it appears inevitable that the interpretation of the statement on page 56 that the listed space recommendations "should be considered the minimum" will result in their implementation as hard, engineering standards, and that any justification for providing less space than the "minimum" will be met by a high bar indeed. As a matter of precedent, OLAW's current guidance on whether IACUC's may approve deviations from the cage density recommendations states in part, "Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non animal welfare considerations are not acceptable."

In summary, MCW does not recommend OLAW's adoption of the 8th edition of the Guide for the following reasons:

a. The new recommended space for breeding rodents will result in significant additional costs to institutions and research programs.

b. There is no scientific basis to support the recommended increase in space; therefore, the added costs to implement the recommendations would be for no demonstrable benefit.


Comment 2:
It will be feasible for the Medical College of Wisconsin to complete a semiannual program and facility evaluation using the 8th edition of the Guide by March 31, 2012. By that date, this institution will be able to determine the extent to which its animal care and use program conforms to the new Guide recommendations. However, we do not think it feasible to have implemented all of the new recommendations contained in the 8th edition of the Guide in that time frame. In particular, it would be unreasonable to expect that institutions could implement the new space recommendations for breeding rats and mice by the end of March next year without simply culling breeding stock and thus cutting back or curtailing research projects.

298 04/20/2011 at 04:46:19 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

299 04/20/2011 at 04:49:07 PM Self McLean Hospital, Harvard Medical School Watertown, MA Comment 1:
NO. Many of the recommendations contained in the 2011 Guide are not based on scientific evidence, and could seriously impede progress in research that will benefit public health. Most recommendations will require significant costly alterations for institutions and investigators.

Examples of recommendations that have little scientific basis and could negatively impact research progress are as follows:

The recommendation for use of pharmaceutical-grade drugs: There is no evidence that pharmaceutical-grade drugs would improve animal welfare. Moreover, research could be impeded because commercially available pharmaceutical-grade formulations are often single concentrations that make it difficult or impossible to manipulate drug dose or to compare different vehicles. Moreover, pharmaceutical-grade drugs will increase the cost of pharmacological research by 500 to 1,000 times in some instances.

Recommendations for Constraints on multiple procedures in animals: It is often in the best interest of science to conduct longitudinal studies in animal subjects using repeated measures in an own control design. Some nonhuman primates live for more than 25 years, and repeated measures are often necessary to answer research questions. Repeated surgeries are often necessary to repair or prolong the life of surgically implanted experimental devices.

Recommendations for Paired housing for nonhuman primates: Despite the attractive "face validity" of paired housing and the opportunity for physical contact between pairs of nonhuman primates recommended in the 2011 Guide, this would place animals at risk for injury and death. Aggression in response to any surprise (a novel noise, person, pain, etc.) may lead the dominant member of the pair to attack/kill the weaker or more submissive cage mate. Studies that require implantation of any device such as an IV catheter to evaluate medication effectiveness could not be conducted.

Recommendations for Changes in cage size: There is no scientific justification for modifications in cage sizes and configurations specified in the 1996 edition of the Guide. The cost to institutions and to investigators would be astronomical!


Comment 2:
Implementation of any changes to the 1996 Guide should be delayed for at least five years (March 2015) to allow NIH to gather scientific evidence to support or to refute the many problematic recommendations proposed in the 2011 Guide. The requirement for additional oversight will add to an already onerous regulatory burden that eventually will be unsustainable for many research institutions. The ultimate impact will be serious damage to this nation's preeminent leadership in health-related research.

The NIH must recognize that lobbying efforts by groups opposed to all research with animals, such as the Humane Society of America and the Physicians for Social Responsibility, are reflected in the proposed changes to the Guide. It would be most unfortunate if NIH standards for insuring animal welfare were primarily influenced by the well-funded political agenda of those organizations opposed to all research on animals, rather than humane concerns for animal welfare and commitment to advances in science.

300 04/20/2011 at 04:56:01 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

301 04/20/2011 at 04:56:31 PM Self     Comment 1:
I cannot recommend acceptance of this document in it's current form. The document represents a drastic change from historical version switching from advisory to regulatory. Further, the cost of implementation, particularly with respect to rodent housing, will have marked implications on the quantity and quality of research that can be performed as housing facilities will host less animals, there will be a significant increase in initial capital requirements - at a time that my institution is facing another 92 million dollar budget cut (and has already sustained 120+ million in cuts in the previous 4 years) and the obvious increase in the costs of animals will have major implications on our research funding in this grant period and beyond. Implementation of this guide at the current time is ill-advised and in many cases (admittedly, within the document) based on poor scientific evidence.

Animal research models are critical for the long term implementation of NIH-funded research, as well as research funded by other organizations, and the long-term effects that the new version of the guide would have on such research could be devastating. I strongly urge you not to consider this guide until significant c hanges are made.


302 04/20/2011 at 05:12:11 PM Self     Comment 1:
The NIH should NOT adopt the eighth edition Guide.


303 04/20/2011 at 05:25:21 PM Self     Comment 1:
NO! The new policies represent an unjustified infringement on scientific decision-making by PHS grantees, contractors and IRGs.

They result in more expenses without any enhancement of animal welfare.


Comment 2:
To allow collection of relevant data, institutional compliance should be deferred until at least march 2015.

304 04/20/2011 at 05:27:41 PM Self Oberlin College Oberlin OH Comment 1:
It should not be adopted.

There are many reasons but I wish to emphasize the increased intrusion on scientific research that is not based on sufficient scientific data. The fact that the increased intrusiveness will increase the costs to teacher/scholars at smaller institutions may have devastating effects on students. What appears to be small changes to a committee in Washington will nudge significant numbers of scientists at small liberal arts colleges to move away from animal research (it has already happened and this would make it worse) thus stunting the experience and world view of many of those students who are now going on to get PhDs.


Comment 2:
This too is excessive for small institutions.

305 04/20/2011 at 05:34:09 PM Self     Comment 1:
I have considerable concern about the increased floor space requirement for female mice with litters to 51 square inches. This new requirement essentially eliminates the potential for continuous breeding of trio groups (1 male, 2 female) in standard sized mouse caging and will significantly increase the time and cost burden of mouse research, which comprises >90% of research animals used in most animal care programs. There there is no scientific justification for this change, it imposes a strict engineering standard regardless of litter size, and it will have a signficant negative impact on the ability of mutant strains to reproduce due to the exclusion of shared maternal nurturing and failure to utilize the post-partum estrus. I urge the NIH to not adopt the 2011 version of the Guide until this new requirement is specifically excluded. I also agree with all of the other statements made in the NABR response to the potential adoption of the 2011 ILAR Guide by the NIH as the standard for laboratory animal care, which is available at http://click.icptrack.com/icp/relay.php?r=15987687&msgid=326524&act=RZO4&c=248297&destination=http%3A%2F%2Fwww.nabr.org%2FNABR_Draft_Comments_On_Guide_MSWord.aspx


Comment 2:
See above and the NABR response to the proposal to utilize the 2011 Guide. I feel this version should not be implemented and the 1996 Guide should remain the officially recognized document until the 2011 version of the Guide is revised sufficiently to remove the costly and unnecessary burden on research that its current form imposes.

306 04/20/2011 at 06:19:27 PM Self     Comment 1:
I would strongly suggest that NIH does not accept the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) that appeared in the Federal Register on February 24, 2011 (76 Federal Register 10379 – 80).

This guide has several flaws including guidelines which would appear to become rules. I am particularly focusing on the new guidelines for rodent housing which have been developed by "judgment and experience" (direct quote from the document) rather than scientific research. To subject researchers across the country to regulations developed by feel and individual use and not directly from controlled studies (or reflective of my individual use) is clearly not correct and certainly beneath the scientific underpinning of NIH.

Time must be given for the discussion of the new guidelines (and adequate space for online submission) to be fully vetted by parties that will be subject to these guidelines and the possibility that needed modification can occur before simply adopting the document.

Thank you for listening and considering these comments from just a regular researcher out in a lab whose research and budget will be severely impacted by the adoption of these guidelines.


307 04/20/2011 at 06:50:12 PM Self     Comment 1:
I do NOT support NIH's adoption of the new Guide for the Care and Use of Laboratory Animals.

Major organizations like the American Psychological Association (APA), the Association for Behavior Analysis International (ABAI), and the American Society for Pharmacology and Experimental Therapeutics (ASPET) have outlined many of the concerns that researchers in this country, like me, have with the new guide. I support their statements regarding the adoption of the new Guide and have little to add. In short, the major concerns I have deal with increased cost to institutions without any clear benefit or empirically supported improvement in animal welfare.

The wording of the new Guide, if adopted, would result in virtual mandates (the "should" comments) that would increase expenditures, e.g., new caging, no multiple procedures, restrictions on food and water intake, increased paperwork, use of pharmaceutical-grade agents (Guide p. 31), without any data to suggest that the new policies are an improvement over the current practices. For example, many researchers have used non-pharmaceutical-grade drugs for decades with no ill effects to the animals. Switching to pharmaceutical-grade drugs would only add cost without improvement to animal welfare. This is just one example where the Guide's recommendations, which would become "law" for many IACUCs, are not empirically supported and would pose an unreasonable burden on researchers and institutions.

While many animal researchers support guidelines for maintaining and improving animal welfare, the new Guide, which lacks empirical support for many recommendations, misses the mark. Of course, animal welfare is important to scientists, but asking institutions to change practices at enormous financial costs without data to support the necessity of the changes, is misguided. In sum, I strongly believe that the NIH should NOT adopt the new Guide.


Comment 2:
n/a

308 04/20/2011 at 07:58:15 PM Self     Comment 1:
NO, it should not adopt it.

the Eighth Edition of the Guide for the Care and Use of Laboratory Animals is a clear example of over-regulation. The issue of a new guide was considered and deemed unnecessary a while back, yet here we have a new draft. Furthermore this guide seeks to empower animal investigation committees that have proven much easier to infiltrate by animal rights activists. Often our only recourse to sanity has been the federal regulations. At the very least it seems to me you should have a broad and extensive consultation with animal researchers to fully consider the consequences of these regulations vis a vis their potential benefits. The process up to now seems arbitrary and unnecessarily rushed.


Comment 2:
No, there should be no seminannual program and facility evaluation using the eighth edition of the guide

309 04/20/2011 at 08:06:31 PM Self     Comment 1:
I oppose the adoption of the eighth edition. After reviewing the proposed guide, I am struck by the large increase in regulation and paperwork for investigators and research institutions. This increase would make conduct of important research more expensive, in an economic situation that makes funding of research harder to provide. At the same time, increases in scientific research are critical to our economic recovery. I know of no evidence that the current regulations fail to adequately ensure the safety and humane treatment of research animals. In all, it is


310 04/20/2011 at 08:40:40 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

311 04/20/2011 at 08:42:59 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
Response:

OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

312 04/20/2011 at 09:14:33 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data, if indeed, the Guide is used to direct policy. It is the data that should guide policy decisions.

313 04/20/2011 at 09:40:07 PM Organization University of Maryland Baltimore, MD Comment 1:
I oppose the adoption of the new edition of the guide. The eighth edition contains many unjustified revisions, and appear making many poorly informed assertions. The goal of medical research is to find new treatments for illnesses by scientists based on their best training and knowledge. Deferring judgement on what quality and quantity of new preparations on animal testing from scientists to regulatory bodies for animal care ans welfare is inappropriate.


314 04/20/2011 at 11:48:44 PM Self     Comment 1:
I would encourage continued use of the 1996 guide. Use of pharmaceutical grade drugs would increase the cost of doing research, and decrease the amount of research being done.


Comment 2:
4 years would be a much more reasonable amount of time. The changes proposed will be expensive, and require time.

315 04/21/2011 at 07:10:42 AM Self     Comment 1:
As a research psychologist involved in NIH-funded research, I am submitting comments on the proposed adoption and implementation of the 8th edition of the Guide for the Care and Use of Laboratory Animals (new Guide) as Public Health Service (PHS) Policy. I have carefully reviewed and compared the new Guide to existing PHS Policy, which is based on the 7th edition of the Guide (1996 Guide). Because research with laboratory animals is an integral component of my research, I strongly support efforts to improve laboratory animal welfare but, at the same time, believe that it is necessary to ensure that proposed policies or regulations are soundly based and do not compromise scientific research. As a result, while the new Guide appears to be a well-crafted resource that aims to strike a balance between the needs of research and the welfare of laboratory animals, at this time I cannot recommend that NIH adopt the 8th edition of Guide as PHS Policy. In particular, I am concerned that: 1) the new Guide contains many recommendations that will, in effect, function like regulations, rather than the "guidelines" for the care and use of research animals authorized by the Health Research Extension Act of 1985; 2) insufficient scientific evidence is presented regarding impact on animal welfare for some major revisions reflected in the new Guide; and 3) the additional provisions will have a significant economic impact on PHS-assured institutions. Therefore, I believe that the 1996 Guide should remain PHS policy and that the new Guide be used as a reference document. Given that the 6000 character limit for comments precludes the ability to provide a detailed response, this response will highlight areas of concern for my own research, as well as that of colleagues in the behavioral and psychological sciences who conduct research with laboratory animals. The new Guide contains more than 40 statements about what institutions "must" do (defined as "actions that are imperative and mandatory duty requirements"), including 29 newly-stated requirements. In addition, there are approximately 660 recommendations that researchers "should" do (defined as "a strong recommendation for achieving a goal" but noting that "individual circumstances might justify an alternative strategy"). Both sets of statements have the unintended consequence of being viewed and implemented as policy rather than guidance – policies that the research community has not had a chance to review and comment on in a substantive manner. Furthermore, some of these mandatory requirements are particularly problematic because they constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. The new Guide is extraordinarily prescriptive on a number of topics, without empirical evidence that the recommended action enhances the welfare of the lab animals. Compliance with these new standards will greatly increase the cost of conducting research with laboratory animals with no evidence of commensurate improvement in animal welfare. The increased cost will be further compounded by increased regulatory and paperwork burden, in terms of justifications, requests for exceptions, and additional recordkeeping. Areas of particular concern are: (a) IACUC responsibilities – new requirements for post-approval monitoring and formal review of "unexpected outcomes" will require additional staffing and recordkeeping; (b) Surgery -- the caution against multiple major survival surgical procedures not only increases costs because of the increase in number of animals required, but also interferes with the scientific integrity of the study by not allowing the use of within-subject and single subject designs that are particularly powerful for behavioral research; (c) Food/fluid regulation – a new requirement to keep written records of both daily food and fluid consumption for animals under either restriction precludes the use of commonly used automatic watering devices, even when water is not restricted. Further, the recommendation that "a highly preferred food or fluid be used as positive reinforcement, instead of restriction" for "conditioned-response research protocols" is made despite information provided in the cited papers that such strategies do not work well to train behaviors – one of many examples of guidance that is inappropriate, both scientifically and for ensuring appropriate use of laboratory animals; (d) Use of Non-Pharmaceutical Grade Chemicals and Other Substances – this new policy is based on false premises. For example, not only do very few commercially available preparations exist that are suitable as tools for experimental research but they are also subject to formulation errors. Also, in psychopharmacological research, including studies such as those I conduct, the commercially available preparations would need to be altered (diluted to particular dose concentrations and filtered), increasing rather than decreasing the margin of error. Given that these commercial preparations are also substantially more expense, this is an increased regulatory burden, with concomitant expense, but with no evidence of benefit. I concur with the National Association for Biomedical Research (NABR) that the new Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB). Therefore, an opportunity for comment in greater detail from the research community on the substance of the new Guide and its financial consequences is necessary before a decision on the adoption of the new Guide as PHS Policy is made and an implementation strategy instituted.


Comment 2:
If the Office of Laboratory Animal Welfare does decide to adopt the new Guide as PHS Policy, I strongly believe that the March 2012 deadline for compliance with the new standards is unrealistic and recommend a more gradual 4-5 year phase-in. Changes in requirements for cage sizes, watering systems, pharmaceuticals, etc. would require purchase of new equipment, all without concomitant changes in NIH funding for the projects affected. Given that budgets for currently funded projects were not developed with the new policies in mind, adoption by March 2012 would, in many cases, represent a substantial financial burden. Further, institutions would require time to prepare for the increased paperwork and regulatory burden, which may involve hiring of new personel and development of new accountability systems - burdens which the institutions will be required to bear without the opportunity for advance financial planning.

316 04/21/2011 at 07:41:57 AM Self     Comment 1:
April 12, 2011

To Whom It May Concern,

I am quite concerned about the mouse breeder cage occupancy guidelines as proposed in the most recent Guide for the Care and Use of Laboratory Animals. The 51 in2 requirement for a single female with a litter would make monogamous pairing the only possible housing arrangement for the standard mouse cage (81 in2). This will dramatically increase the cost of maintaining mice and is counter to what is reported in the scientific literature on the effects of housing density on mouse biological parameters.

Peters A, Festing M. Population density and growth rate in laboratory mice. 1990. Lab Anim 24:273-279.

Smith AL, Mabus SL, Stockwell JD, Muir C. Effects of housing density and cage floor space on C57BL/6J mice. 2004. Comp Med 54:656-663.

Smith AL, Mabus, SL, Muir C, Woo Y. Effects of housing density and cage floor space on three strains of young adult inbred mice. 2005. Comp Med 55: 368-376.

Davidson LPO, Chedester AL, Cole MN. Effects of cage density on behavior in young adult mice. 2007. Comp Med 57:355-359.

Laber K. Veatch LM, Lopez MF, Mulligan JK, Lathers DM. Effects of housing density on weight gain, immune function, behavior and plasma corticosterone concerntrations in BALB/c and C57BL/6 mice. 2008. J Am Assoc Lab Anim Sci 47:16-23.

In addition, the guidelines go beyond the European guidelines as outlined in the Council of European Convention which is counter to attempts to harmonize guidelines between different geographic regions..

For most academic institutions in the United States the options are to house breeding mice in monogamous pairs or purchase all new caging. One of the problems with housing mice in monogamous pairs is that there is less social interaction between mice, and it is my experience based upon work with rodents for over 25 years that mice breed better in a social setting.

In short, the specific requirement to house a female male with a litter at 51 in is a bad standard and should be changed to be more consistent with European standards (a single male and two females in a standard sized mouse cage).

Respectfully Submitted,

*****


Comment 2:
recommend implementation one year after OLAW acceptance.

317 04/21/2011 at 08:02:59 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

318 04/21/2011 at 08:57:53 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

319 04/21/2011 at 09:19:07 AM Self     Comment 1:
No.Oppose approval of the new guide


320 04/21/2011 at 09:24:51 AM Organization BRAINnet foundation Sam Fransisco, CA Comment 1:
No, the NIH should not adopt the 8th edition of the Guide. There is no supporting data for the proposed changes.


321 04/21/2011 at 09:34:51 AM Self     Comment 1:
The new restrictions and costs associated with adopting the new Guide will impose upon significant additional burdens on researchers. As far as I can see, there are no data to indicate the Guide needs changing. It is not clear what problems the changes are trying to remedy. There is no empirical justifications that the additional measures and restrictions will result in a significant improvement in animal welfare. Finally, the additional costs and paperwork are unduly burdensome, especially for institutions that have limited funds.


322 04/21/2011 at 10:51:50 AM Self     Comment 1:
NO! This new version substantially rewrites policy, and does so in contradiction to a great deal of literature on animal welfare, including some of the literature it cites for support! In its present form it will severely restrict ongoing research and impose huge costs across biomedical research.


Comment 2:
I do not agree with the implementation plan for using the eighth edition as the basis for evaluation by March 31, 2012. This shoud be postponed until Mar. 2015 to allow the correction of errors in the eight edition, and to permit sufficient time to upgrade facilities.

323 04/21/2011 at 10:54:45 AM Self     Comment 1:
The adoption of these proposed guidelines, which seem to have been formulated without any scientific data, will significantly increase the obstacles to the development of new disease treatments. I urge the Public Health Service to reject these changes.


324 04/21/2011 at 11:07:45 AM Self     Comment 1:
I feel that the guide should not be accepted in its present form. I specifically have issues with the non-pharmaceutical grade drug policy. There is no reliable data suggesting that the mandated use of pharmaceutical grade drugs (PGD) will increase the health or welfare of research animals. The use of PGDs will have several negative consequences. 1) needless expense, there are huge differences in the cost of PGD vs chemically pure versions of the same drug. Cost is a major issue in view of the diminishing research dollars that are provided at taxpayers expense. Pure cost-benefit analysis alone makes this a ridiculous policy. 2)PGDs are less readily available. The commercial formulations of PGDs make precise and accurate pharmacological studies (dose-response, toxicology) very difficult because of the inactive and active ingredients, difficulties in dilution, administration, compounding etc. 3) New/experimental compounds are not PGD, the time and bureaucratic expense of documenting and justifying non PGDs in unnecessary and unwarranted and does not provide any benefit to the animals involved.


325 04/21/2011 at 11:30:09 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


326 04/21/2011 at 11:35:07 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

327 04/21/2011 at 11:42:31 AM Organization Wake Forest University Health Sciences Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an ?update? of the 1996 Guide, however the final product is twice as long and contains a great deal of new ?policy.? Compliance with these new ?policy? statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from ?should? statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have ?overregulated.? Moreover, the new ?Guide? policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, na?ve and constraining section on choices of ?chemicals and other substances? to give animals and specific guidance on ?post-approval? monitoring (e.g., observation of procedures). In addition the new ?Guide? requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

328 04/21/2011 at 12:31:33 PM Organization Aragon Pharmaceuticals San Diego CA Comment 1:
We are opposed to the new requirement that new cage sizes for continual pair mating in a cage that is 65 square inches cannot be done – the female would have to be separated from the male. This greatly reduces the productivity of the maiting, leading to increased animal use, increased husbandry costs or a significant investment in new capital equipment.


329 04/21/2011 at 12:45:36 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

330 04/21/2011 at 12:53:21 PM Self     Comment 1:
No. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

331 04/21/2011 at 01:01:16 PM Self     Comment 1:
please don't

more paperwork without scientific justification.


Comment 2:
please don't

332 04/21/2011 at 02:08:36 PM Organization Wake Forest University Health Sciences Winston-Salem, NC Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

333 04/21/2011 at 02:13:36 PM Self     Comment 1:
Retain the 1996 guide


Comment 2:
If new guidelines are adopted, extend compliance date to March 2015.

334 04/21/2011 at 02:16:35 PM Self     Comment 1:
I think that the guide should NOT be adopted for evaluation of institutional programs.


335 04/21/2011 at 02:16:53 PM Self   Morganton, NC 28655 Comment 1:
I vote against adopting the new Guide as policy, maintaining adherence to the 1996 Guide. A similar public comment period in 2005–2006 yielded the conclusion that no substantive revisions to the existing Guide were needed.


Comment 2:
If the 2011 Guide is adopted as PHS policy, I suggest a time frame of at least 4 years (e.g., 2015)in which PHS-assured institutions and NIH intramural programs should be required to comply given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

336 04/21/2011 at 02:16:57 PM Self     Comment 1:
The newest edition of the guide has a great deal of useful new information. There is a discussion of the 3R's for the first time, along with a clarification of what constitutes an animal care and use program. The protocol review section has been expanded to cover unexpected events and humane endpoints, along with expansion of food/fluid regulation. The section on post-approval monitoring is particularly timely. The new sections on aquatics and specialized animal facilities (imaging, etc) provide relevant guidance to both scientists and veterinarians. The quality & quantity of new guidance far outweighs any concerns regarding additional compliance requirements/suggestions (i.e., new musts/shoulds).


Comment 2:
This is a sufficient period of time following release of the new Guide to incorporate changes into existing animal care and use programs.

337 04/21/2011 at 02:17:46 PM Self     Comment 1:
THE PROPOSED CHANGES ARE TOO COMPLEX AND WILL INCREASE THE COST OF RESEARCH WITHOUT INCREASING THE SAFETY OR HEALTH OF LABORATORY ANIMALS.THESE CHANGES SHOULD NOT BE IMPLEMENTED.


338 04/21/2011 at 02:19:14 PM Self     Comment 1:
I believe that the 1996 Guide is sufficient (as was concluded in the 2005-06 assessment), and vote against adopting the new guide.


Comment 2:
Research institutions are struggling with severe budget cutbacks. At least 4 years should be provided.

339 04/21/2011 at 02:25:54 PM Self     Comment 1:
Do not adopt.

The guide will increase the authority of local IACUCs to restrict already peer-reviewed research.

Although some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food and liquid restriction).


Comment 2:
I recommend a 4 year deadline given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

340 04/21/2011 at 02:26:43 PM Self     Comment 1:
I vote OLAW should retain the 1996 Guide as PHS policy


Comment 2:
I STRONGLY recommend at least 4 years if not more (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions!!!

341 04/21/2011 at 02:27:03 PM Organization The Kolburne School New Marlboro, MA Comment 1:
I recommend that the 8th edition in it's current revision NOT be adopted as a standard for the use and care of animals in a laboratory setting. Furthermore, I recommend the 1996 standards stay in effect until the 8th edition can be further refined.


Comment 2:
I vote against this timeline. I recommend at least 4 years (March 31, 2015) given the expense of a variety of cage size and housing requirements during a time of great financial difficulty for research institutions.

342 04/21/2011 at 02:29:50 PM Organization University of North Texas Denton, TX Comment 1:
Consider at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.


343 04/21/2011 at 02:33:37 PM Self     Comment 1:
I recommend that the OLAW NOT adopt these new guidelines as policy. I feel that the 1996 version of the Guide is sufficient and that no substantial changes to the current Guide is warrented or necessary.


Comment 2:
I believe that, if the 8th edition of the Guide is adopted, full-scale implementation of it should not be required for at least four (4) years (i.e., 2015). The nation, as a whole, is faced with extreme economic difficulties at present, and these new incurred costs will be detrimental to sceintific research.

344 04/21/2011 at 02:37:42 PM Self     Comment 1:
The NIH should not adopt these guidelines.


Comment 2:
Four years (2015) seems like a more appropriate time frame.

345 04/21/2011 at 02:37:48 PM Self     Comment 1:
The current regulations are quite sufficient and the onerous increases proposed would put many productive research laboratories under tremendous financial strain, hindering their ability to contribute to the greater good of their field and public health in general. These guidelines are not based in empirical research. Animals utilized for research purposes are incredibly healthy, and every effort is already made to ensure their continued vitality and to minimize pain and distress during and following any procedure.


Comment 2:
At a time of great financial difficulty for our research institutions, who are competing for ever fewer research dollars, putting taxpayer dollars in to superfluous regulatory activities is not the rational choice. Many, many laboratories simply would not have the funds to meet the new requirements, and many hardworking and productive researchers and graduate students would be left with no way to pursue their ideas and goals for new research.

346 04/21/2011 at 02:38:05 PM Self     Comment 1:
I wish to vote against adopting the new Guide as policy.


347 04/21/2011 at 02:40:59 PM Self     Comment 1:
Adopt.


Comment 2:
Standardized fidelity of implementation checklist completed by local site manager, with simultaneous inter-observer agreement data collected by NIH supervisor.

348 04/21/2011 at 02:41:20 PM Self     Comment 1:
Re: NIH's Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals

My comments regarding the National Institutes of Health's solicitation of comments concerning the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) that appeared in the Federal Register on February 24, 2011 (76 Federal Register 10379 – 80) are as follows:

(1) The 2011 Guide contains many recommendations that will, in effect, function like regulations, rather than the "guidelines" for the care and use of research animals authorized by the Health Research Extension Act of 1985 (2) There is insufficient scientific evidence for some revisions reflected in the new Guide; (3) The additional provisions of the 2011 Guide will have a significant economic impact on PHS-assured institutions such as my home institution, The University of Arizona.

I ask that NIH not adopt the new Guide until the above concerns are addressed. I suggest that the 2011 Guide be reviewed for consistency with the Office of Management and Budget's (OMB) Bulletin No. 07-02: Final Bulletin for Agency Good Guidance Practices, specifically the definitions, standards, notice and public comment provisions regarding "significant guidance document[s]", "economically significant guidance document[s]" and "regulatory action" (72 Federal Register 3432-40).

In view of the Guide's general applicability, scope, depth, complexity, and effect of setting NIH policies regarding the humane care and use of laboratory animals in PHS supported activities, it is reasonable to assume that NIH's adoption of the 2011 Guide would qualify the Guide as a "guidance document" as defined by OMB. To follow all the Guide's provisions in order to qualify for NIH awards, the more than 1,100 PHS-assured institutions will likely spend a minimum of $100 million annually. I believe changes in the guide will significantly increase the cost of research at our insitution, which will impact our ability to continue biomedical research goals, which relate directly to human health and welfare. I believe it is imperative for the animal research community to have a meaningful opportunity to comment on the substance of the new Guide and its financial consequences so that NIH can formulate an appropriate, well-informed implementation plan.

Thank you.


Comment 2:
I believe you need to delay your plan by one year, given the signficant issues that remain before implementation and the difficulty research facilities will have in fully evaluating and complying with this extensive document.

349 04/21/2011 at 02:41:32 PM Self     Comment 1:
I recommend that you DO NOT ADOPT as policy the eighth edition of the new Guide, that you continue to maintain adherence to the 1996 Guide as policy.

Many state budgets - as here in Texas - have huge deficits that are resulting in major cuts to education. The new Guide would suffice to be the deathknell to many of our research programs.

Furthermore, many of the recommended policies in the eighth Guide are not empirically supported. That these are mandated without having been exposed to scientific rigor is curious indeed.


Comment 2:
Should the eighth Guide be adopted, please postpone the implementation until 2015. Perhaps that would give us time to more thoroughly investigate your proposals. Indeed, it would give the scientific community a bigger window in which to prepare for the mandated changes.

Thank you for this opportunity to comment.

350 04/21/2011 at 02:43:12 PM Organization Behavioral Pharmacology Division of ASPET Chapel Hill, NC Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

351 04/21/2011 at 02:47:26 PM Organization Charles River Laboratories Wilmington, Massachusetts Comment 1:
Charles River Laboratories recommends that OLAW not accept the 2011 Guide in its present form. The Guide to be valuable must be clear in its recommendations, recommend practices that have a robust scientific base in the peer-reviewed literature, minimize or eliminate unintended consequences, take into account the myriad of confounding variables that may make recommendations inappropriate, and consider the impact on limited research resources. While the 2011 Guide has many positive aspects particularly in providing detailed explanations of recommended practices as well as the rationale behind them, in certain sections its guidance is unclear. The strength of some recommendations appear to exceed the robustness of the available data, and difficulties in practical application of the guidance appear not to have been appropriately considered. Previous editions, as well as the 2011 edition, leave room for professional judgment at an institutional level to apply performance standards in order to tailor practices and facilities to the needs of research animals. While the 2011 Guide acknowledges this principle, it frequently sets forth as minimum recommendations new engineering standards, new strong recommendations, and certain new prohibitions. These new standards while similar to ETS 123 do not include the same caveats as that guidance and like the standards in ETS 123 are not not adequately supported by peer-reviewed scientific studies. The level of specificity of guidance needs to be proportional to the robustness and specificity of the science supporting it. Charles River does not believe that the 2011 Guide meets this standard in several key areas. In the case of the 2011 Guide, for example, the new cage space allocations for a mother with litter for rats and mice do not appear to be supported by robust science; yet, they will have substantial unintended consequences in terms of costs for compliance, on adherence to the principles of the three Rs, and depending upon how compliance is achieved, on animal welfare. In Charles River's analysis, even if the substantial costs for implementing these new space recommendations were set aside, there is no scientifically supported proportionate benefit to the welfare of these animals that warrants these new recommendations to be considered as minimum. In some cases, not only is guidance not supported by scientific evidence, it is contradictory to other guidance such as is the case in requiring that floor space occupied by enrichment items be subtracted from the total floor area—a clear disincentive to using floor mounted rodent enrichment devices. Other unintended consequences will occur by tightening the relative humidity ranges for animal areas that is worded as a strong recommendation and is not support by scientific data, yet, will have a substantial operational and equipment cost impact on most facilities. In this case, the strength of the recommendation is disproportionate to any theoretical positive animal welfare impact. Clarification of the interpretation and application of this recommendation is not only needed but any strict application of this guidance should be justified at an institutional level based upon experience, engineering considerations, and professional judgment. Overall, Charles River recommends that OLAW gathers more detailed information on issues associated with changes in the 2011 Guide than allowed by this comment mechanism before making the final decision on acceptance. Based upon these concerns, an analysis of both scientific justification and the financial impact of new guidance should be undertaken, especially if it is to be applied as a minimum standards or strong recommendations. The decision on how the Guide will be used can then be made on a rational basis in proportion to the amount and strength of evidence supporting proposed changes in guidance.


Comment 2:
Charles River Laboratories believes that it is appropriate that each institution should begin to make an assessment of areas of compliance and noncompliance with new guidance as set forth in the 2011 Guide. The deadline for this evaluation as suggested by OLAW seems to be appropriate. However, Charles River strongly urges that OLAW requests that the evaluation include, in addition to a time table for compliance, a feasibility and economic impact statement for correcting areas of noncompliance. Certainly such an evaluation is in keeping with Charles River's recommendation for a more robust analysis of the new recommendations found within the 2011 Guide. Based upon this analysis, OLAW should decide if the Guide will be accepted as written and, if so, should all recommendations be implemented; and where significant economic impact is identified, should guidance be provided outlining reasonable and perhaps institutional-specific schedules for conformance or will certain recommendations require further scientific justification by an independent body such as the National Academy of Sciences perhaps using a group other than the Guide Committee assembled for this purpose. While animal welfare is an important component of biomedical research activities, recommendations for the care and use of laboratory animals need to be based on sound science and must consider the amount of resources that will be required to implement them. If such recommendations are limited or are uncertain in their established ability or level of improvement of animal welfare, if they are based principally on professional judgment, or if they do not consider all the variables that might impact their desired effect, they cannot be considered to be useful as universal guidance. Moreover, they do not warrant wide spread application or the expenditure of disproportional amounts of the ever decreasing resources available for the research community that will be required to implement them. Charles River has calculated its additional costs for implementing some of the recommendations within the Guide and has found them to conservatively exceed $100 million. Charles River believes that this level of expenditure coupled with the estimate from other rodent and rabbit breeders, as well as the costs from the research community, merits more consideration of the strength of the scientific support for these recommendations before implementation should be considered.

352 04/21/2011 at 02:48:37 PM Self LSU Health Sciences Center New Orleans, LA 70112 Comment 1:
No - this should not be adopted. This will lead to additional expenses to the institution and the investigators with no real enhancement of animal welfare. This will also cause an additional paperwork burden to the investigator


Comment 2:
One area where this could lead to a major problem is with the requirement to use pharmaceutic preparation of drugs in animals. These steps will not increase animal welfare (particularly in the use of drugs like pentobarbital for non-survival surgery or euthanasia), but will lead to astronomical increases in the costs to the investigators.

353 04/21/2011 at 02:49:05 PM Self     Comment 1:
I think that it is absolutely necessary to adopt the new guidelines from the Guide for the Care and Use of Laboratory Animals (8th Edition). Not adopting them would be completely irresponsible as scientists looking to uphold the highest standards and integrity in science. The excuse that it shouldn't be adopted because it will make certain research "harder or more expensive" is a ridiculous excuse. In addition, providing research animals better conditions could actually lead to more accurate research, by reducing animal stress which could affect outcomes in certain research.


Comment 2:
I think that it is necessary to require institutions to complete a semiannual program and facility evaluation. In the past there have been instances of institutions not meeting the previous standards and with making the standards more extensive, more facilities will be looking at ways to get around the requirements and not adhere properly.

354 04/21/2011 at 02:51:12 PM Self     Comment 1:
I hope OLAW will retain the 1996 Guide as PHS policy.

A great deal of the new policy promises to significantly increase a) the expense of research, b) the paperwork burden on researchers, and c) the authority of local IACUCs to restrict already peer-reviewed research. While some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food and liquid restriction).


Comment 2:
I recommend at least 4 years given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

355 04/21/2011 at 02:56:11 PM Self     Comment 1:
As a practicing scientist, I applaud the efforts to maintain the highest levels of care for animals in research. There are a number of specific concerns, however, with the latest version of the Guide. To begin with, the new Guide is nearly twice as long as the 1996 version, and contains a great deal of new policy that promises to significantly increase (a) the expense of research, (b) the paperwork burden on researchers, and (c) the authority of local IACUCs to restrict already peer-reviewed research. Some of the new recommendations are based on empirical research, but many are not (e.g., cage sizes, food and liquid restriction). There are no reasons to suspect that these additional burdensome and costly requirements would produce any improvement in animal care and welfare, although it would likely produce erosion in the quality of research and the number of top scientists working in areas that have significant benefits for both humans and animals. Researchers care deeply about their animal subjects, and the protection and care has served science and the animals well. There is little compelling reason to adopt new guidelines when those in the 1996 Guide continue to serve the community and the animals so well.


Comment 2:
If the 2011 Guide is adopted as PHS policy, then the deadline for full compliance that is proposed in the Federal Register is March 31, 2012. Such a date places extreme burden and excessive costs on institutions (including government funding). At least 4 years (e.g., 2015) seems not unreasonable given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

356 04/21/2011 at 02:58:22 PM Self     Comment 1:
I do not think there is a need for a new version and do not think the eighth edition should be adopted.


Comment 2:
I recommend waiting at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

357 04/21/2011 at 03:06:04 PM Self     Comment 1:
I find myself in agreement with the ACNP position, copied below:

"NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures."


358 04/21/2011 at 03:09:42 PM Self   Sarasota, FL Comment 1:
I vote against adopting the new Guide as policy, maintaining adherence to the 1996 Guide. No substantive revisions to the existing Guide are needed.


Comment 2:
I recommend at least a 4-year time frame (e.g., 2015) for whatever plan is adopted. This would take into account the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

359 04/21/2011 at 03:20:23 PM Self     Comment 1:
I feel like these guidelines will be a positive thing for science. Such guidelines and restrictions are desperately needed in the world of research. Most labs only adhere to the bare minimum of standards and is it has stood, that simply isn't enough. Monkeys, apes, and even rats and pigeons are living creatures and deserve to live in healthy, comfortable environments, especially if they are going to be subjected to scientific tests.


Comment 2:
I also feel this would be beneficial to science and the animals involved.

360 04/21/2011 at 03:28:21 PM Self   Charlotte, North Carolina Comment 1:
Do not adopt the eigth edition of the Guide, it would be an unecessary burden.


Comment 2:
This would be an necessary burden.

361 04/21/2011 at 03:32:29 PM Organization University of Nevada, Reno Reno, NV Comment 1:
I do not endorse adoption of the eight edition. The new revisions do not in any way enhance treatment of existing laboratory animals and levy unnecessary expenses on scientists. The 1996 edition of the guide is more than sufficient to secure humane treatment of animals in a research context.


Comment 2:
I unequivocally reject the eight edition and endorse the continued use of the 1996 guide as a standard of practice.

362 04/21/2011 at 03:37:27 PM Self     Comment 1:
I am against implementation of the policies as they are written. Should changes to animal housing be required, I suggest that institutions be given at least 4 years to make those changes, due to the costs and logistical difficulties of mandatory changes to housing.


363 04/21/2011 at 03:37:54 PM Organization McLean Hospital Belmont, MA 02478 Comment 1:
Response: NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

364 04/21/2011 at 03:39:20 PM Self     Comment 1:
NIH should NOT adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals. This guide is too long, it will increase the expense of research, and recommendations such as limiting food and liquid restriction are NOT based on empirical research.


Comment 2:
NIH should NOT adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals. However, if this guide is adopted, compliance should not be required for a minimum of 4 years, given the expenses associated with compliance.

365 04/21/2011 at 04:07:43 PM Self     Comment 1:
The eighth edition of the Guide should NOT be adopted. Adherance to the 1996 Guide should be maintained.


Comment 2:
I recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

366 04/21/2011 at 04:17:19 PM Self MPRC, University of Maryland Catonsville, Maryland Comment 1:
NO


367 04/21/2011 at 04:24:57 PM Self     Comment 1:
NIH should NOT adopt the eight edition of the "Guide for the Care and Use of Laboratory Animals (Guide)" as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals other than humans.


Comment 2:
NIH should NOT adopt the implementation plan which would require that institutions complete at least one semiannual program and facility evaluation using the eight edition of the Guide as the basis for evaluation by March 31, 2012.

368 04/21/2011 at 04:27:53 PM Organization University of Virginia Charlottesville Comment 1:
I stand strongly AGAINST adoption of the new edition of the Guide. There is not adequate justification for supplanting the 1996 Guide as PHS Policy. There are also numerous problems with the new Guide as federal policy. In particular, I am opposed to the new guidelines for the use of medical grade compounds, newly introduced requirements for post-approval monitoring of IACUC-approved protocols and formal review of "unexpected outcomes". I also oppose the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures, as well as the section on "Food and Fluid Regulation" which requires that food and fluid consumption be recorded daily for all animals on either type of restriction. Each of these changes would force the use of more animals and/or drive up the research costs unnecessarily.


369 04/21/2011 at 04:29:24 PM Self     Comment 1:
I believe that the proposed new Guide contain equirements that are not substantiated by empirical research. I strongly recommend that the 19969 standards be maintained.


Comment 2:
If new Guide's standards are adopted rather than retaining the 1996 standards, it is unreasonable to believe that research faciliites will be able to implement them financially and in terms of other resources in less than 1 year. New research endeavors ought to have two (2) years to implement the Guide while a four year phase in period ought to be allowed so that research protocols can be completed under the 1996 Guide's requirements when the research protocol was developed and funded.

370 04/21/2011 at 04:34:27 PM Self     Comment 1:
I urge that this new addition be put on hold. It should NOT go into effect. This new addition goes a long way towards INCREASING costs, INCREASING paperwork, INCREASING roadblocks to research, INCREASING the number of animals utilized in research, and INCREASING time to conduct research. However, it will markedly DECREASE the ability to conduct research in an efficient manner. Particularly onerous is the section titled "Use of Non-Pharmaceutical Grade Chemicals and Other Substances". Not only is it unnecessary, but it will totally block new and innovative research. Rules (euphemistically called guidelines) such as these will markedly slow the progress being made in improving health for the American people and helping people live longer and healthier lives.


Comment 2:
Implementation plan should not be put into effect until a final version is agreed upon. Otherwise, it becomes a "fait accompli" and adds to the burden of the scientist, the institution, and research, in general.

371 04/21/2011 at 04:36:42 PM Self UAMS Little Rock, AR Comment 1:
I am a member of the College on Problems of Drug Dependence (CPDD), from whom I am sure you have heard already. CPDD welcomes the opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy. CPDD recommends that the 8th edition not be adopted as PHS Policy. While it contains some useful new information (e.g., on care of aquatic species), there are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. Instead, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry. The 8th edition departs significantly from the 7th, which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
CPDD concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

372 04/21/2011 at 04:37:41 PM Self     Comment 1:
I recommend against the adoption of these guidelines. The science behind many of these recommendations is questionable. The added expense of the methods and the added paperwork burden on investigators and support staff will increase the cost to the taxpayer to produce less research. At a time when the US can ill afford to put itself at a disadvantage in its ability to conduct innovative biological and behavioral research, these standards are proposed. The effects on animal health and well being are questionable (at best). The effects on research, technology, innovation, and the number of bright young US researchers that choose to pursue animal research is almost assured. I strong oppose the proposed revised guidelines.


Comment 2:
I strongly oppose this. See prior comment for reasons supporting this opposition.

373 04/21/2011 at 04:40:08 PM Organization UNT Health Science Cente Fort Worth, TX Comment 1:
1) Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. These are unnecessary, and more importantly ineffectual, requirements that will substantially increase cost without improving welfare.

2)The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Although OLAW has published a similar set of statements on its website in recent years, the status as enforceable PHS Policy has been controversial due to their de novo introduction of the topic as an answer to a "Frequently Asked Question," (i.e., no previously published PHS Policy nor the Guide had addressed use of drugs in research). No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of, first, the USDA/APHIS Policy 3, an interpretive rule for use of pharmaceutical grade "medications" to prevent pain/distress in the conduct of research; and second, the NIH policy for its intramural program on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement has made clear that Policy 3 is interpreted to require use of commercially prepared solutions, rather than those prepared by investigators; the first sentence of the new Guide section on this topic is consistent with this view. Yet the NIH policy defines "pharmaceutical grade" drugs as those manufactured according to USP standards, thus accommodating the practice of preparation of drug solutions in the laboratory. Yet even that intramural NIH Policy ignores the fact that the NIDA drug supply program, which has been operating to supply compounds to funded researchers for decades, does not prepare to USP standards, because they are unnecessary for research purposes. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking. Yet, as with other sections, the contradictions in guidance were not recognized by those who published the 2011 Guide.

3) The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. Again, these are unnecessary regulations that will be costly and ultimately ineffective, particularly as there is substantial evidence that food restricted animals are healthier due to suffering less obesity-related health disorders.


374 04/21/2011 at 04:43:16 PM Self     Comment 1:
Response: NO. Many of the recommendations contained in the 2011 Guide are not based on scientific evidence, and could seriously impede progress in research that will benefit public health. Most recommendations will require significant costly alterations for institutions and investigators.

Examples of recommendations that have little scientific basis and could negatively impact research progress are as follows:

The recommendation for use of pharmaceutical-grade drugs: There is no evidence that pharmaceutical-grade drugs would improve animal welfare. Moreover, research could be impeded because commercially available pharmaceutical-grade formulations are often single concentrations that make it difficult or impossible to manipulate drug dose or to compare different vehicles. Moreover, pharmaceutical-grade drugs will increase the cost of pharmacological research by 500 to 1,000 times in some instances.

Recommendations for Constraints on multiple procedures in animals: It is often in the best interest of science to conduct longitudinal studies in animal subjects using repeated measures in an own control design. Some nonhuman primates live for more than 25 years, and repeated measures are often necessary to answer research questions. Repeated surgeries are often necessary to repair or prolong the life of surgically implanted experimental devices.

Recommendations for Paired housing for nonhuman primates: Despite the attractive "face validity" of paired housing and the opportunity for physical contact between pairs of nonhuman primates recommended in the 2011 Guide, this would place animals at risk for injury and death. Aggression in response to any surprise (a novel noise, person, etc.) may lead the dominant member of the pair to attack/kill the weaker or more submissive cage mate. Studies that require implantation of any device such as an IV catheter to evaluate medication effectiveness could not be conducted.

Recommendations for Changes in cage size: There is no scientific justification for modifications in cage sizes and configurations specified in the 1996 edition of the Guide. The cost to institutions and to investigators would be astronomical!


Comment 2:
Response: Implementation of any changes to the 1996 Guide should be delayed for at least five years (March 2015) to allow NIH to gather scientific evidence to support or to refute the many problematic recommendations proposed in the 2011 Guide. The requirement for additional oversight will add to an already onerous regulatory burden that eventually will be unsustainable for many research institutions. The ultimate impact will be serious damage to this nation's preeminent leadership in health-related research.

The NIH must recognize that lobbying efforts by groups opposed to all research with animals, such as the Humane Society of America and the Physicians for Social Responsibility, are reflected in the proposed changes to the Guide. It would be most unfortunate if NIH standards for insuring animal welfare were primarily influenced by the well-funded political agenda of those organizations opposed to all research on animals, rather than evidence-based humane concerns for animal welfare and commitment to advances in science.

375 04/21/2011 at 04:47:59 PM Organization Yale University New Haven CT Comment 1:
The 8th edition departs significantly from the 7th,,which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
CPDD concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

376 04/21/2011 at 04:52:45 PM Self   Essex Fells, nj Comment 1:
I support these changes.


Comment 2:
I support these changes.

377 04/21/2011 at 04:55:16 PM Self     Comment 1:
I oppose the adoption of the 8th edition of the guide. This edition introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish.Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research. The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields.


Comment 2:
2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

378 04/21/2011 at 05:06:14 PM Self     Comment 1:
I am strongly opposed to adoption of the 8th edition of the Guide in its present form. Some of the mandatory requirements (e.g. housing, use of non-pharmaceutical grade drugs) are either unreasonable or impossible to follow without a dramatic adverse impact on the integrity of certain types of behavioral science. In many ways, the new Guide represents and intrusion into second-guessing the scientific and professional judgment of investigators and veterinarians in their fields of research.


379 04/21/2011 at 05:11:01 PM Self     Comment 1:
I recommend that the 8th edition NOT be adopted as PHS Policy. While it contains some useful new information (e.g., on care of aquatic species), there are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. Instead, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry.

The 8th edition departs significantly from the 7th,, which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions.

Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations."

The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy.

The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research (e.g., compounds from the NIDA drug supply program, reliable private vendors, professional chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use of "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
I concur with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more...." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

380 04/21/2011 at 05:17:53 PM Self     Comment 1:
I am AGAINST adoption of the new edition of the Guide. Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements relating to housing requirements and drug sourcing would result in significant increases in costs to NIH, at a time when NIH funding is shrinking.


381 04/21/2011 at 05:27:01 PM Self     Comment 1:
I am against adopting the new Guide. It would create an unreasonable burden on investigators and ACUCs, and increased cost to research institutions, but no real enhancement of animal welfare.


Comment 2:
I am against implementing the new Guide. If it is implemented, there should be a grace period of about three years for already approved animal-study protocols.

382 04/21/2011 at 05:29:38 PM Self UNCW Wilimington, NC Comment 1:
I think that the strict "guidelines" for how an institution and a researcher must alter their current practices for animal care and use is excessively restrictive. I think many of the demands placed on Institutions will require excessive oversight and paperwork, and in turn, excessive costs to maintain quality research.

Additionally, I am unclear why new guidelines are required. Is there empirical evidence that current standards are resulting in undue stress or pain in animals. Are unjustified experiments taking place at alarming rates?

I am a current member of IACUC, and the participation of scientists at the University in cooperation with local vets and members of the public seems to result in high standards of animal care at our university. The goal of every scientist conducting research is to have a healthy, well cared for animals. It is in our own best interest to care for our animals, and I have not witnessed any threats to animal welfare in any labs I've ever visited; at our university or any other.

With the already high standards of care, I reiterate my confusion as to why we need these stricter "guidelines" (which honestly read more like mandates). I think that the unnecessary cost of implementing these unsubstantiated standards would prohibit much of my research, and I suspect many other scientists would feel the same way. Many facilities currently conducting ethical and justified research would not meet many of the standards set in the new guide, and I for one do not support shutting down good research to meet unsupported changes.

I am a member of APA, and I support their official response to this request for public comment. I would not recommend adopting the guide in its current state.


383 04/21/2011 at 05:53:01 PM Self   Portland, Oregon Comment 1:
NO. The new guide is supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy."

Compliance with these new "policy" statements may increase the expense to my research though the cost of pharmaceutical grade drugs and may preclude testing some compounds if I can not obtain the appropriate "grade" drug.However, the scientific data justifying these policy changes is non-existent.

Adherence to the 2011 Guide will require large increase in paperwork burden with justifications in order to deviate from the new policies.

The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Specifically the constraints on multiple procedures, new requirements for food- or fluid-restriction, the choices of chemicals and post-approval monitoring of procedures will add to the cost of the research.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

384 04/21/2011 at 06:16:32 PM Self     Comment 1:
I am voting against the new guide as a policy andI recommend that the 1996 Guide should be retained.


Comment 2:
I suggest least 4 years (e.g., 2015), given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

385 04/21/2011 at 06:17:01 PM Self University of New Hampshie Durham, NH Comment 1:
I have served as Principal Investigator of grants from NIMH and NSF since the early 1960s, and the use of animals in my behavioral research complied with guidelines in effect throughout those years. The animals' health remained excellent throughout each study; many of them (pigeons) lived for more than 12 years and served in several diffeent studies. There is no need to alter the guidelines.


Comment 2:
If the standards are to be changed, additional funds will be required and time will be needed to meet mandated conditions. especially for animal housing.

386 04/21/2011 at 06:25:38 PM Self     Comment 1:
The eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) should NOT be adopted. The 1996 guide should be maintained.


Comment 2:
If the eighth edition of the Guide is adopted, a period of at least 4 years (ie, 2015) should be allowed for transition to the new guidelines. Given the substantial expense of changing to new cage size and housing guidelines and the current economic strains on researchers, 2012 is NOT a reasonable goal for implementation of the eighth edition of the Guide.

387 04/21/2011 at 06:47:40 PM Self     Comment 1:
No. I oppose the approval of the new guide. Compliance with the new policy statements (for example, cage sizes) will increase the expense to institutions and investigators, and result in an extraordinary increase in paperwork. However, there is little to no scientific support for the changes, and there is no identifiable improvement in animal welfare.


Comment 2:
Data should guide policy. Institutional compliance should not be required in the absence of scientific support.

388 04/21/2011 at 07:19:28 PM Organization International Study Group for Investigating Drugs as Reinforcers Washington, D.C. Comment 1:
The College on Problems of Drug Dependence (CPDD) is the oldest U.S. scientific society on drug dependence. Originally founded in 1929 as part of the National Academy of Sciences, CPDD now is an independent scientific society comprised of ???? members.. It serves researchers, clinicians, and policy makers to promote research and facilitate the transfer of findings to improve drug abuse treatment and prevention practices. CPDD welcomes the opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy. CPDD recommends that the 8th edition not be adopted as PHS Policy. While it contains some useful new information (e.g., on care of aquatic species), there are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. Instead, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry. The 8th edition departs significantly from the 7th,,which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
CPDD concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

389 04/21/2011 at 07:24:31 PM Self     Comment 1:
I am against the adoption of the eighth edition of the Guide for the Care and Use of Laboratory Animals. The new addition contains many additions/revisions from the previous version that do not improve the care or welfare of laboratory animals, but do increase costs to the NIH, researchers, and institutions.


Comment 2:
I am against using the new Guide as the basis of facility evaluation.

390 04/21/2011 at 07:25:42 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

391 04/21/2011 at 07:35:20 PM Organization Louisiana State University Health Sciences Center, New Orleans, LA Comment 1:
I am strongly opposed to these new guidelines as they would add an unwarranted burden to researchers using laboratory animals.

If the NIH adopts the new guidelines presented in the 8th edition of the Guide for the Care and Use of Laboratory Animals, this will place an enormously increased burden upon researchers performing many types of animal experiments. For example, the guidelines suggest the use of pharmaceutical-grade chemicals (which, in the case of pentobarbital is approximately ten times the price of its non-pharmaceutical counterpart!).

Although I feel it is extremely important for researchers to always be open to improvements in the care and use of laboratory animals, I was unable to find any references in the 8th edition to documentation of any specific deleterious effects (either scientific or regarding unnecessary animal suffering) arising from current guideline practices to justify these burdensome changes.

Although the 8th edition guidelines do not completely preclude the use of non-pharmaceutical grade chemicals, their alternative suggestion was for researchers to give consideration to at least twelve different parameters for each chemical used, without providing specific justification for each parameter. I am very concerned that this list would leave investigators open to an extremely burdensome justification process that, as noted above, I consider to be unwarranted.


392 04/21/2011 at 07:35:28 PM Organization ACADIA Pharmaceuticals San Diego, CA Comment 1:
No. Increased investigaitor burden (cost, paperwork) with no data supproting new regualtions.


393 04/21/2011 at 07:37:16 PM Organization Eastern Oregon University LaGrande, OR Comment 1:
NIH should NOT adopt this new policy. The 1996 policy has been sufficient and adopting the new policy will have significant impacts on research and teaching.


Comment 2:
No, institutions already need to have internal review by research review committees. Additional paperwork and policy will only burden this committee and hinder research and teaching.

394 04/21/2011 at 07:39:39 PM Self     Comment 1:
Yes, adopt the new guidelines immediately! It is the most correct and ethical behavior.


Comment 2:
Yes, adhere and comply by the earliest deadline to follow these guidelines. It is correct and ethical behavior.

395 04/21/2011 at 08:02:11 PM Self     Comment 1:
Although resource intensive, stricter guidelines for the humane care and use of laboratory animals is long overdue. Please move forward with these regulations.


Comment 2:
Again, this is a necessary part of using live beings in laboratory research. As stated in the proposed guide: "Each institution should establish and provide sufficient resources for a Program that is managed in accord with the Guide and in compliance with applicable regulations, policies, and guidelines." Scientific research, development and application are important, but humane treatment should be non-negotiable, and evaluation of facilities would be a logical means toward fidelity of the guidelines.

396 04/21/2011 at 10:28:36 PM Self     Comment 1:
I have read through much of the guide and was struck by a number of general statements that would be problematic and intrusive in daily research efforts. Many of these statements are vague and appear to make arbitrary distinctions. This sort of guidance is more likely to lead to unnecessary delays and expenses in research. As someone who studies the neural mechanisms of ingestive behavior the statement below concerns me: "In the case of conditioned-response research protocols, use of a highly preferred food or fluid as positive reinforcement, instead of restriction, is recommended."

This is something that we routinely do and I can attest that animals do not always acquire tasks when given preferred food. A mild food restriction is often necessary in these studies. Most importantly, what is the basis for making this recommendation? Is there something unhealthy about mild restriction? In fact, the vast majority of research across animal phyla indicate that food restriction improves many health parameters. Even after restriction, our animal models are still heavier than a similar animal in the wild.


Comment 2:
No, I do think this guide, in its current from should serve as the basis for evaluation in a year. There is a need for more discussion of its implications - both financial and scientific.

397 04/22/2011 at 12:08:32 AM Self     Comment 1:
It not should adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals. The advancement of science, especially in human behavior drastically benefits from animal laboratory experiments.


398 04/22/2011 at 03:20:20 AM Self     Comment 1:
As a behavioral scientist, I vote against adopting the new Guide as policy,and I recommend maintaining adherence to the 1996 Guide. The new guide contains requirements that are not based on scientific evidence. These requirements will lead to costly changes that are not necessary, and these added expenses will likely lead to the loss of some laboratories. The existing standards for the IACUC oversight process are entirely adequate for the ethical use of animals for research.


Comment 2:
If the new guidelines are accepted, the time frame for implementation is not realistic. Additional funding would be required to meet the new standards. I recommend that at least 4 years be allowed for preparation to meet the new standards, if adopted.

399 04/22/2011 at 03:26:23 AM Self   Reno, NV Comment 1:
Yes: stricter standards are needed. As a scientist, there will be limitations to such research in the future, but it is much more important that we are looking out for the "well-being" of our subjects.


Comment 2:
This would be a good change: again, stricter standards will lead to research that is not only in the interest of the animals involved, but also the quality of the studies that pass these tests will be of a much higher caliber than is currently the case.

400 04/22/2011 at 07:14:08 AM Organization The Jackson Laboratory Bar Harbor, Maine Comment 1:
The Jackson Laboratory has long worked successfully through our IACUC to ensure appropriate implementation of the provisions of the Guide to safeguard animal welfare at our facility. The updated (8th edition) Guide contains some areas of concern. Previous comment opportunities on the new Guide pre-dated the availability of a published document. Now that it is in print, The Jackson Laboratory supports opening a comment period prior to OLAW adopting the updated Guide. Specifically, we support the use of performance standards rather than strict engineering standards as the best means of achieving optimal animal welfare within the unique environments of different institutions. The new guidelines as written could have unintended effects on research, and potentially on animal welfare. An example is the new space requirements for female mice with litters. The IACUCs are in the best position to develop appropriate performance standards, and we believe they should retain the flexibility that now allows them to make responsible animal welfare decisions at the institutional level. The fiscal impacts of the updated Guide could, depending on how the document is categorized for implementation purposes, have a major economic impact on biomedical research institutions throughout the country. For these reasons we respectfully request a more substantive opportunity for comment.


401 04/22/2011 at 08:26:50 AM Self     Comment 1:
As a physician and NIH-funded researcher, I am greatly concerned with the changes that are proposed to be implemented in the new Guide. While my concerns are many and deep, below are the points that I feel are most concerning. I strongly request that the changes in the Guide not be implemented until a careful consideration has been given to their multiple detrimental impacts and substantial changes made.

1. There is no indication that wholesale changes needed to be made in the Guide. There were only a few areas that needed updating in the previous edition.

2. Many (~60) of the changes aren't "guidelines," they are mandatory changes that will need to be made, removing investigator and IACUC scientific judgment from the process.

3. There is no scientific justification (and often conflicting evidence) for many of the changes suggested. This is especially true for the cage sizes. Implementing these changes for rodents will cost several hundred million dollars in direct (infrastructure) and indirect (impaired research) costs.

4. Implementation of regulatory guidelines like these that are projected to cost >$100,000,000 should receive more careful consideration as to their benefits and costs, and be backed by accepted scientific findings.

5. Strongly discouraging multiple use of animals (even for a "within subject design") will have the unintended consequence of driving up animal use and associated expenses. This is a direct conflict with the "Reduce" part of the "3-R's", which is a guiding fundamental animal use in research.

6. Recommending that positive reinforcement rather than mild food restriction be used in conditioned response experiments ignores substantial data that positive reinforcement does not work well to train behaviors such as self administration.

7. The introduction of the requirement that IACUC approve the use of non-pharmaceutical grade chemicals including formulation and a host of details that are required for FDA approval of drug administration to humans is unworkable, inappropriately transfers responsibility from the investigator to the IACUC (who generally lack the expertise to make these evaluations), and ignores the fact that the data required to implement this requirement is lacking for most drugs that would be administered to animals.

8. Additional duties assigned to the IACUC are excessively burdensome to the IACUC members and to the experimenter, again slowing down research and increasing the administrative burden, with no measurable benefit to the experimental animals. The most onerous of these is direct comparison of approved protocols to what is being done in the lab, and "formal review" of unexpected outcomes.


Comment 2:
Semiannual investigations are fine, basing them on the eighth edition is not. (Since the 8th edition is fundamentally flawed.)

402 04/22/2011 at 08:35:28 AM Self     Comment 1:
I am AGAINST adoption of the new edition of the Guide for the Care and Use of Laboratory Animals. This new 8th edition departs significantly from the 7th. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions.


403 04/22/2011 at 08:50:54 AM Self     Comment 1:
NO. I concur with the response offered by the ACNP, which is restated here. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
I concur with the response of the ACNP, which is that OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

404 04/22/2011 at 09:17:21 AM Self Binghamton University (SUNY) NY Comment 1:
I am againts the the edition of the guide


405 04/22/2011 at 09:18:16 AM Self University of Massachusetts Amherst, MA Comment 1:
In especially these times of fiscal constraints, the imposition of additional and unneeded regulations is unwarranted. In addition to their adverse consequences for research, the proposed regulations would pose further difficulties for the conduct of laboratory sections of academic courses, Please simply reaffirm the 1996 regulations. Thank you.


406 04/22/2011 at 09:30:39 AM Self     Comment 1:
The 8th edition of the Guide should not be adopted. It too stringent and impedes the progress of scientific research.


Comment 2:
Program and facilities evaluations are necessary and I support them, however, I do not support the use of the 8th edition of the Guide as the the basis for evaluations.

407 04/22/2011 at 09:42:55 AM Self     Comment 1:
The College on Problems of Drug Dependence (CPDD) is the oldest U.S. scientific society on drug dependence. Originally founded in 1929 as part of the National Academy of Sciences, CPDD now is an independent scientific society comprised of 5997 members. It serves researchers, clinicians, and policy makers to promote research and facilitate the transfer of findings to improve drug abuse treatment and prevention practices. CPDD welcomes the opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy. CPDD recommends that the 8th edition not be adopted as PHS Policy. While it contains some useful new information (e.g., on care of aquatic species), there are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. Instead, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry. The 8th edition departs significantly from the 7th,,which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
CPDD concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

408 04/22/2011 at 10:10:00 AM Organization Tufts University Medford, MA Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

409 04/22/2011 at 10:14:20 AM Self     Comment 1:
As an investigator at a primarily undergraduate institution, I have serious concerns about the new restrictions and costs that adopting the new Guide will impose upon researchers. This guide was clearly intended for large, research-first institutions that have many animal colonies overseen by professional staff, and that have adequate institutional or grant funding to incur additional administrative costs. Of particular concern to me is that these guidelines will make it prohibitively difficult for smaller institutions to establish and maintain quality research facilities. Many thousands of research laboratories exist at such institutions, and they are often capably staffed by the investigators themselves, not a professional staff. The animals under such care are not "warehoused" as they may be at other institutions, and receive careful, humane treatment and care under the current guidelines. The additional guidelines in the new version of The Guide will not change animal care at such institutions, but will mandate additional costs that could jeapordize the willingness of administration to have animal colonies on campus. Is there data to indicate that the Guide needs changing? What is that data? If the guide is adopted, it could mean the end of research for many investigators, thus taking away the opportunites for undergraduate students who want to pursue a career in the biomedical sciences. My fear is that the additional costs and paperwork required by the new guide will be unduly burdensome, especially for those institutions that teach undergraduates and have limited funds.


Comment 2:
The additional burdens placed on researchers and institutions by implementing this guide could mean the end of research for many investigators, especially at smaller, primarily undergraduate institutions where support for animal research facilities is not as strong as "research-first" institutions. This would mean taking away the opportunites for undergraduate students interested in the biomedical sciences. My fear is that the additional costs and paperwork required by the new guide will be unduly burdensome, especially for those institutions that teach undergraduates and have limited funds.

410 04/22/2011 at 10:18:51 AM Self     Comment 1:
I am opposed to adopting this. This new edition of the Guide includes a large number of new regulations which will impede laboratory research. Very little empirical evidence has been provided that show any sort of cost benefit analysis supporting these new policies. I would expect NIH to base their decisions on a careful consideration of the costs to grantees and their institutions as well as the possible benefits to animal welfare.


Comment 2:
Providing less than one year to implement this is unrealistic and does not allow enough time to evaluate its financial impact.

411 04/22/2011 at 10:32:28 AM Self Virginia Commonwealth University Richmond, VA 23298 Comment 1:
Many of the "guidelines," which usually end up becoming mandates by regulatory bodies, interfere with the conduct of research without enhancing or even harming the well-being of the animal subjects. Two examples follow:

Page 56: "Floor space taken up by food bowls, water containers, litter boxes, and enrichment devices (e.g., novel objects, toys, foraging devices) should not be considered part of the floor space." This does not into consideration that the animal can walk or climb on or through the enrichment device or carry it around (paper cups, cardboard tubes). These new standards could greatly restrict research where space is at a premium and will require employing personnel who police this.

Page 119: "Careful monitoring increases the likelihood of successful surgical outcomes (Kuhlman, 2008). Monitoring includes routine evaluation of anesthetic depth and physiologic functions and conditions, such as body temperature, cardiac and respiratory rates and pattern (Flegal et al. 2009), and blood pressure (Kuhlman 2008), and should be appropriately documented." I completely disagree with this statement. In rodents, successful surgical outcomes are best assured by clean, efficient surgeries that do not require supplemental anesthetic or longer exposure to gas anesthesia than necessary. Not only is it difficult to measure these physiological signs in rodents, doing so requires distraction from the surgery that increases anesthetic exposure and encourages break from aseptic technique. In surgeries involving pregnant or immature rodents it is especially important to limit the duration of the surgical procedure, as this will limit the overall exposure of the immature brain to anesthetic agents, which are known to adversely impact the developing nervous system (for a review, see Wang and Slikker, Anesthesia and Analgesia, 106: 1643, 2008).


412 04/22/2011 at 11:01:51 AM Organization CPDD Bridgewater, NJ Comment 1:
The College on Problems of Drug Dependence (CPDD) is the oldest U.S. scientific society on drug dependence. Originally founded in 1929 as part of the National Academy of Sciences, CPDD now is an independent scientific society comprised of ???? members.. It serves researchers, clinicians, and policy makers to promote research and facilitate the transfer of findings to improve drug abuse treatment and prevention practices. CPDD welcomes the opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy. CPDD recommends that the 8th edition not be adopted as PHS Policy. While it contains some useful new information (e.g., on care of aquatic species), there are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. Instead, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry. The 8th edition departs significantly from the 7th,,which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
CPDD concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

413 04/22/2011 at 11:26:54 AM Organization McLean Hospital Belmont, MA Comment 1:
NIH should not adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals .

1 VOTE NO.

There are many reasons not to approve this Guide, here are some: 1. Increased economic cost to the scientists and to the institution 2. Increased administrative cost in terms of additional burdensome paperwork 3. Increased costs if pharmaceutical-grade drugs are required 4. Increased costs and injury to animals if the proposal to require social housing for nonhuman primates is required 5. The constraints on conducting multiple procedures in animals and a requirement for "post-approval monitoring" of procedures


Comment 2:
NIH should not implement a plan requiring institutions to complete semiannual programs using the eighth edition of the Guide for at least five (5) years.

414 04/22/2011 at 11:45:59 AM Self   Springfield, MA Comment 1:
I oppose additional restrictions on cage size and liquid or food deprivation of laboratory animals. The costs incurred from compliance with these changes will severely impair the ability of researchers to continue their critical work in the areas of behavioral pharmacology, neuroscience, and basic behavioral processes. As an applied researcher, I am certain that a decrease in non-human research will also eventually affect the quality and pace of research conducted by me and my colleagues. The trickle-down implications of these cost-prohibitive regulations cannot be understated.


Comment 2:
I think that semiannual review of revised guidelines would be reasonable. However, if the full Guide is ultimately accepted, I would support a deadline for compliance no earlier than 2015 to avoid disrupting or derailing critical research.

415 04/22/2011 at 12:08:10 PM Self     Comment 1:
My particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
I concur with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

416 04/22/2011 at 12:09:00 PM Self     Comment 1:
I am against the adoption of the new edition of the Guide.

The 2011 Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish. Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. A major change in the Guide is the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures. This echos a caution in which investigators are strongly discouraged from advocating animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research. The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. This may represent only imprecision in drafting, but is only one example of guidance that is inappropriate. The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields.


Comment 2:
I am against the adoption of the new edition of the Guide.

The 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

417 04/22/2011 at 12:09:10 PM Organization UCSD San Diego, CA Comment 1:
I appreciate the opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy to govern research at PHS-Assured institutions. I beleive that there is not adequate justification for supplanting the 1996 Guide as PHS Policy and that there are numerous problems with the new Guide as federal policy. Our comparison of the 7th and 8th editions lead us to conclude that the 8th edition represents a significant departure from the 7th. Although it includes much new information, it also incorporates new policies in a number of areas. Of particular concern is the extent to which the 2011 Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish. Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. A major change in the Guide is the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures. This echos a caution in which investigators are strongly discouraged from advocating animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research. The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. This may represent only imprecision in drafting, but is only one example of guidance that is inappropriate. The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Although OLAW has published a similar set of statements on its website in recent years, the status as enforceable PHS Policy has been controversial due to their de novo introduction of the topic as an answer to a "Frequently Asked Question," (i.e., no previously published PHS Policy nor the Guide had addressed use of drugs in research). No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of, first, the USDA/APHIS Policy 3, an interpretive rule for use of pharmaceutical grade "medications" to prevent pain/distress in the conduct of research; and second, the NIH policy for its intramural program on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement has made clear that Policy 3 is interpreted to require use of commercially prepared solutions, rather than those prepared by investigators; the first sentence of the new Guide section on this topic is consistent with this view. Yet the NIH policy defines "pharmaceutical grade" drugs as those manufactured according to USP standards, thus accommodating the practice of preparation of drug solutions in the laboratory. Yet even that intramural NIH Policy ignores the fact that the NIDA drug supply program, which has been operating to supply compounds to funded researchers for decades, does not prepare to USP standards, because they are unnecessary for research purposes. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking. Yet, as with other sections, the contradictions in guidance were not recognized by those who published the 2011 Guide. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify their use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the intrusion of the new Guide into second-guessing scientific and professional judgment of experts in their fields of research. This represents only one of many examples of greater burdens on the IACUC, and by extension staff, imposed by new requirements.


Comment 2:
CPDD concurs with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

418 04/22/2011 at 12:18:33 PM Organization Johns Hopkins University Baltimore, MD Comment 1:
The Johns Hopkins University appreciates the opportunity to offer comments on the 8th edition of the Guide for the Care and Use of Laboratory Animals. We applaud the efforts of the ILAR revision committee that has expanded and updated the previous edition of The Guide.

Although the 8th edition contains useful new information (e.g., on the care of aquatic species), it otherwise represents a significant departure from the 7th edition in ways that impose unjustified new constraints on research design, new paperwork burdens, and new costs (for both equipment and personnel) on institutions receiving federal funds for research. We believe these significant changes come without a concomitant increase in animal welfare and will therefore diminish the quality of essential biomedical research.

Johns Hopkins University therefore supports the position of the National Association for Biomedical Research (NABR) in its letter to Francis Collins urging that the NIH not adopt the new Guide until and unless concerns regarding new regulatory burdens are addressed through evaluation of the 8th edition of the Guide as a "significant guidance document under the Office of Management and Budget's Bulletin No. 07-02, "Final Bulletin for Agency Good Guidance Practices."


Comment 2:
The Johns Hopkins University concurs with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . . ." Therefore, setting a date by which PHS-Assured institutions must comply with the new Guide prior to an OMB analysis of its financial impact on those institutions and on the National Institutes of Health itself is premature.

419 04/22/2011 at 12:35:13 PM Self     Comment 1:
I am quite concerned about the proposed increases in required cage sizes. I sit on a university committee related to animal use, and can say from that experience that space allocation for animal research is a huge concern. As I'm sure is true for many other institutions, we include additional vivarium space with any new building project to stay ahead of demand. However, the new space would be woefully inadequate to address the new standards. Further, all institutions are heavily invested in caging. Replacement of current caging systems would require an enormous amount of funding. It seems to me the justification given for these new requirements is insufficient, considering their impact.


Comment 2:
I can't imagine that institutions could possibly put into effect the changes that this program would require in less than a year's time. Further, I would hope the regulations will be significantly revised before they must be used by anyone.

420 04/22/2011 at 12:37:50 PM Self     Comment 1:
The College on Problems of Drug Dependence (CPDD) is the oldest U.S. organization concerned with drug dependence research. Originally founded in 1929 as part of the National Academy of Sciences, CPDD is an independent, leading scientific society in the drug dependence field. It serves researchers, clinicians, and policy makers to promote understanding of the many facets of drug abuse to the benefit of all involved in drug and alcohol research and to facilitate the transfer of scientific findings to successful treatment and prevention practices. CPDD welcomes this opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy to govern research at PHS-Assured institutions. CPDD's conclusion is that there is not adequate justification for supplanting the 1996 Guide as PHS Policy and that there are numerous problems with the new Guide as federal policy. Our comparison of the 7th and 8th editions lead us to conclude that the 8th edition represents a significant departure from the 7th. Although it includes much new information, it also incorporates new policies in a number of areas. Of particular concern to CPDD is the extent to which the 2011 Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish. Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. A major change in the Guide is the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures. This echos a caution in which investigators are strongly discouraged from advocating animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research. The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. This may represent only imprecision in drafting, but is only one example of guidance that is inappropriate. The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Although OLAW has published a similar set of statements on its website in recent years, the status as enforceable PHS Policy has been controversial due to their de novo introduction of the topic as an answer to a "Frequently Asked Question," (i.e., no previously published PHS Policy nor the Guide had addressed use of drugs in research). No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of, first, the USDA/APHIS Policy 3, an interpretive rule for use of pharmaceutical grade "medications" to prevent pain/distress in the conduct of research; and second, the NIH policy for its intramural program on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement has made clear that Policy 3 is interpreted to require use of commercially prepared solutions, rather than those prepared by investigators; the first sentence of the new Guide section on this topic is consistent with this view. Yet the NIH policy defines "pharmaceutical grade" drugs as those manufactured according to USP standards, thus accommodating the practice of preparation of drug solutions in the laboratory. Yet even that intramural NIH Policy ignores the fact that the NIDA drug supply program, which has been operating to supply compounds to funded researchers for decades, does not prepare to USP standards, because they are unnecessary for research purposes. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking. Yet, as with other sections, the contradictions in guidance were not recognized by those who published the 2011 Guide. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify their use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the intrusion of the new Guide into second-guessing scientific and professional judgment of experts in their fields of research. This represents only one of many examples of greater burdens on the IACUC, and by extension staff, imposed by new requirements.


Comment 2:
CPDD concurs with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

421 04/22/2011 at 12:56:28 PM Self New York State Psychiatric Insitute New York, NY Comment 1:
As chair of an IACUC at a large New York State research facility, I recommend that the 8th edition not be adopted as PHS Policy. There are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. In addition the guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." Never-the-less, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry. The 8th edition departs significantly from the 7th,, which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition; policies that must be followed. The excessive use of the "must" term removes the traditional role of the IACUC in supervising animal work in accordance with locally-based knowledge of the complexities attendant to the specific types of research being conducted at an institution. Thus, the new policies constrain the exercise of scientific and professional judgment. Further any local variation away from the "must" list will entail massive amounts of tedious paperwork that will cost much in time and money and do nothing to improve animal welfare. Higher costs to institutions (not counting the time donated by IACUC members) will have to be passed on to grants through increased direct and indirect costs. What is challenging for scientists working with laboratory animals is the absence of data supported so many of the "must." Data we can work with, hunches and feelings that a change is good is a different matter entirely. I will focus on only a few specific concerns. 1) Mandatory requirements for new cage sizes for some species and for social housing of all species will require large expenditures. The increase in cage size for rodent breeding, based on no data, is particularly troubling. Our institution is modest with about 20,000 rodents but breeding is key especially for mouse work and the increased cost will decrease funding for the science part of the work. 2) Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") places a great burden on the IACUC and its members. Our current PAM practices address adequately address the issues, but the addition more specific review points is a burden. Likely the extra work will entail increasing IACUC size and staff. 3) The language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries ignores both studies that are best done with multiple survival surgeries and long-term studies that based on their length may require motile surgeries. Further restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. Finally, these restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral and psychiatric research. 4) The section on "Food and Fluid Regulation" now requires daily recording of food and fluid consumption for all animals on either type of restriction will increase burden without improving animal care. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. 5) The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" shows a complete lack of understanding research examining drug effects on behavior and studies that manipulate internal states with drugs as pharmacological probes of underlying mechanism. This section essentially bans researchers from using standard source drugs for research including compounds from the National Institute on Drug Abuse drug supply program; reliable private vendors; chemists or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers. Again this is an intrusion into the scientific process without any data justifying the change.

An issue not directly addressed by focusing on the human and financial burden of the new guide is the fact that increasing costs for housing and breeding will decrease money available for the science part of the project. An increase in both direct and indirect costs will decrease funds available to support investigators. Those hurt the most will be junior investigators just getting their careers started. This will put an entire generation of scientists at risk. This is not a minor issue. Recent cutbacks have already significantly disheartened the latest batch of individuals looking for their first research award at my institution. Further cut backs will be devastating in both the short and long terms for progress in medical and psychological science.


Comment 2:
I agree with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made. As chairman of my IACUC I can say with certainty that we will not be prepared to meet the new proposed standards if adopted in such a brief time frame. Physical space and financial restraints would make it impossible. Further the greater demands placed on IACUC membership will make serving on the IACUC an even greater strain on the ability to conduct one's own research and keep one's own funding tenable. I care deeply about the science our researchers conduct and in the proper care of our laboratory animals. What I've seen in the new guide will not improve substantially our animal care but will impede science.

422 04/22/2011 at 01:29:43 PM Self     Comment 1:
No, the eighth edition of the Guide should not be adopted. Many of the changes are unnecessary. Several of the revisions are inconsistent with high quality rodent behavior experiments. Several of the new requirements create additional paperwork that does not add to the quality of animal care and use.


423 04/22/2011 at 01:54:32 PM Organization University of Texas at El Paso El Paso, Texas Comment 1:
The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. There are several problems with this request.

First, there is a lack of a definition of pharmaceutical grade. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review.

Second, it is unclear that this provision will be an improvement over currently used practices. Given that it is a costly suggestion, I worry that a careful cost/benefit analysis has not been done. I personally contacted Sigma INC on this matter when our last veterinarian was encouraging us to purchase Nembutal, over pentobarbitol which wee were purchasing from Sigma. When I called Sigma, they were unclear what this definition meant, especially given that they are a pharmaceutical company. They did describe the careful provisions that they took to ensure the quality of their compounds. They also save portions of lots of their drugs to enable them to go back and re-evaluate the purity of lots. Related to this, is cost and whether it is a valuable use of our research dollars. As an example, a vial of nembutal (or animal sacrifice) is at least 5 times the cost of the same drug that can be purchased and prepared in our own laboratories---using pure compounds purchased from well known pharma compainies. This seems to be an unwarranted request that is difficult to accept given the cuts in NIH funding that we are all experiencing.

On a final note, the 8th edition departs significantly from the 7th, which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. They require additional staffing and or time from researchers who want to stay focused on advancing science while still taking quality care of research animals. Many of these will result in higher costs to grants and to institutions, and importantly, it is not clear that the changes will improve the quality of the animals lives and of the research findings.


Comment 2:
It is unclear whether this revision will improve the quality of animal research over what is currently done. These provisions are potentially costly in money and time and require additional staffing that many institutions cannot afford. A more careful cost/benefit analysis is needed to ensure that this major change is truly warranted.

424 04/22/2011 at 01:56:31 PM Self McLean Hospital Belmont, MA Comment 1:
The 8th edition departs significantly from the 7th,,which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. The requirement for pair/group housing of nonhuman primates is logistically and economically unfeasible for many facilities. It will be prohibitively expensive for many programs to completely redesign and replace their entire animal housing set-up to accommodate this rule. IACUC committees will subsequently be confronted with the unenviable choice of granting broad exemptions or imposing unreasonable economic and labor burdens on investigators. Additionally, this requirement will pose increased health risk to animals including injuries and disease transmission as well as additional risks to staff. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers.


Comment 2:
I concur with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

425 04/22/2011 at 02:18:42 PM Organization Johns Hopkins University School of Medicine Baltimore, MD Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. For example, there is no evidence that using pharmaceutical grade drugs would improve animal welfare or science; 2) commercial pharmaceutical grade formulations make careful pharmacological research difficult as these are single concentration formulations, which makes manipulating dose and vehicle comparisons difficult while at the same time maintaining pharmaceutical grade standard; and 3) The regulation is burdensome without benefit to animal welfare or science.

Adherence to the 2011 Guide will require a large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

426 04/22/2011 at 02:20:41 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

427 04/22/2011 at 02:20:44 PM Self     Comment 1:
Bad idea.


Comment 2:
Bad idea with this guide.

428 04/22/2011 at 02:22:16 PM Self     Comment 1:
There are no valid data justifying the benefits and expense of the proposed eighth edition changes. Adoption would be costly and burdensome to the scientific community.


Comment 2:
No action should be taken until thorough study of the need and justification for changing exiting guidelines.

429 04/22/2011 at 02:29:33 PM Organization The American Association of Immunologists Bethesda, Maryland Comment 1:
The American Association of Immunologists (AAI), a professional association of more than 7,200 of the world's leading research scientists and physicians who are dedicated to elucidating the immune system through basic research, appreciates having this opportunity to express its views on whether the NIH Office of Laboratory Animal Welfare (OLAW) should adopt the recently published 8th edition of the Guide for the Care and Use of Laboratory Animals (Guide). In their research, AAI members use and depend on rodents, and in particular laboratory mice, and therefore have a deep interest in all matters governing their care and use.

Although AAI recognizes, and agrees with, the goal of updating the former Guide – to ensure the humane care of laboratory animals – AAI believes that the revised Guide will have a substantial negative impact on NIH-funded biomedical research. AAI is confident that the Guide can be updated in a way that addresses the humane care of animals, a goal which we strongly endorse, without unnecessarily or inadvertently reducing scientific research capacity or disrupting, impeding, or burdening the research scientists who spend their careers in search of answers and cures. Unfortunately, the revised Guide does not accomplish this objective. As a result, AAI urges OLAW not to adopt or implement the 8th edition of the Guide.

AAI is aware that OLAW has received comments regarding the adoption of the 8th edition of the Guide from the National Association for Biomedical Research (NABR). AAI wholly endorses NABR's comments and shares its substantive concerns. AAI underscores the following points of major concern:

1) The new Guide has not been sufficiently vetted by the scientific community it is meant to serve.

The new Guide is a quantum change from the previous version. The AAI community is one of many that looked forward to a new, modernized Guide that balances the needs of laboratory experimentation with humane animal care. However, the new Guide falls far short of our expectations: in too many cases changes have been mandated without scientific justification. And too often, the new Guide makes generalizations and creates ambiguities both in lines of responsibility and logical application to specific laboratory organisms. AAI will not address specific granular concerns in this solicitation for Public Comment, but AAI would be happy to comment in greater detail at a later date or to meet with OLAW to discuss our detailed concerns. The impact of these concerns is magnified because some language in the new Guide might be construed to prohibit the use of animals in certain experiments that are currently considered humane. Moreover, AAI does not believe that these problems can be solved by OLAW's publication of its interpretation of the new Guide via FAQs. Instead, the problem is with the new Guide itself because reasonable interpretations in the FAQs could, at best, confuse matters further, and at worst, directly contradict what is written in the Guide.

2) New rodent cage space restrictions are not based on substantiated scientific data. The new restrictive cage space policy, unjustified by scientific data, would have far-reaching scientific and financial impact on a breath of Public Health Service supported biomedical research.

A strict interpretation of the new Guide would have tremendous adverse effect and appears to be inconsistent with best, healthy breeding practices. For example, duo (1 male and 1 female) and trio (one male and 2 females) of laboratory mice within the recommendations of the 7th Guide are shown by years of experience to be the most beneficial configurations for litters to survive and thrive. There are no substantiated data that merit a change from the former time-tested policy.

This new policy, if adopted, would require a doubling to tripling of breeding colony to even approach the same productivity. It would also require the dismantlement of caging systems, including racks, designed to comply with the 7th Guide recommendations, and would cost hundreds of millions of dollars and time lost to retrofit caging systems and to expand current animal facilities (including continually incurring husbandry costs). The impact of this scientifically unjustified change is far-reaching because it would not only negatively impact organizations that perform rodent breeding but also drive up the costs for all organizations that purchase laboratory rodents to an unsustainable level. Most importantly, this new restrictive policy is inconsistent with data from multiple peer-reviewed publications evaluating the effects of cage density. Furthermore, data in peer-reviewed papers published since the 7th edition show that a number of common mouse strains can be housed at twice the density recommended by 7th edition of the Guide, in some cases with apparent benefits to health. Therefore, it is troubling from both animal health and financial perspectives that maximum recommended caging densities were not relaxed to reflect this new information.

In conclusion, AAI urges OLAW not to adopt or implement the 8th edition of the Guide until it has been revised, following the solicitation of detailed comments by the scientific community and after careful consideration of the concerns that working scientists have raised. AAI respectfully requests that in the meantime, OLAW continue to use and rely upon the 7th edition of the Guide.


Comment 2:
Because AAI urges OLAW not to adopt or implement the 8th edition of the Guide until it has been revised, following the solicitation of detailed comments by the scientific community and after careful consideration of the concerns that working scientists have raised, AAI does not support NIH's proposed implementation plan.

If NIH does adopt the 8th edition of the Guide, despite the many concerns raised, AAI recommends that NIH delay implementation at least until March 31, 2013, except for life- threatening issues (e.g., cage washer safety).

430 04/22/2011 at 02:34:07 PM Self     Comment 1:
My vote is for OLAW to retain the 1996 Guide as PHS policy.

I am a basic research scientist who studies the behavior of rats in laboratory conditions. My research has been continuously funded by NIH and/or NSF from 1957-2010. I have been a member of our University's IACUC committee, editor or consulting editor of journals with articles on animal behavior, and served as a member of several grant review committees of NIH and NSF related to animal behavior.

My concern is that I knew nothing about the Eighth Edition of the Guide for the Care and Use of Laboratory Animals until today when a colleague asked me to look at it on Friday afternoon, and comment on it by one minute before midnight on Sunday. I was struck by the enormity of the task--this is a large revision with many apparently small modifications with large potential ramifications.

Every semester I teach an advanced undergraduate research course on the behavior of rats, and I currently have three other IACUC protocols. I interact with veterinarians, animal caretakers, administrators responsible for animals, and animal researchers. If I did not know about the plan to adopt these changes, I assume that many others did not know either. This could be a serious problem.

The new Guide for the Care and Use of Laboratory Animals should be used as a "Guide" for the next four years. We should have real experience in these guidelines before the words are given the status of rules.


431 04/22/2011 at 02:39:41 PM Self     Comment 1:
No. I do not favor adoption of the revised Guide. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

432 04/22/2011 at 02:45:06 PM Self     Comment 1:
NO


Comment 2:
NO

433 04/22/2011 at 02:47:03 PM Self     Comment 1:
No


Comment 2:
No

434 04/22/2011 at 02:52:19 PM Self     Comment 1:
The NIH should NOT adopt this "revised" (8th edition) report. It contains many changes that will impede scientific inquiry and progress as well as increase costs in conducting research. Most importantly, there is no evidence provided that many of the indicates changes (e.g., cage size) will, in fact, have any effect on animal welfare per se.


Comment 2:
It seems premature to require institutional IACUC semiannual evaluations to be based on this 8th edition at this time.

435 04/22/2011 at 03:00:37 PM Self     Comment 1:
I strongly oppose adoption of the new Guide for the Care and Use of Laboratory Animals as the 8th edition. The new guide has doubled in size. There is no need for additional rules and regulations. Animal care is already overly regulated. In particular, I cite the following issues as poorly thought out. Several will require enormous added expense and result in no increase in animal welfare. 1. I am opposed to the new mandatory requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species. Implementation of these requirements will require large expenditures of funds to accomplish. 2. I oppose the newly introduced requirements for post-approval monitoring of IACUC-approved protocols and formal review of "unexpected outcomes" of research. Such requirements are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members and are unnecessary. 3. I oppose the new requirement that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems. This is only one example of guidance that is inappropriate. 4. I oppose the newly added section titled "Use of Non-Pharmaceutical Grade Chemicals and Other Substances". This section is particularly problematic because it essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking.


Comment 2:
I believe that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

436 04/22/2011 at 03:02:13 PM Self   Philadelphia, PA Comment 1:
The 8th edition departs significantly from the 7th,,which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. I am against adopting the the 8th addition of the Guide.


Comment 2:
The 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

437 04/22/2011 at 03:06:41 PM Self     Comment 1:
NO. The new Guide includes, without providing clear justifications, many changes that will increase cost of animal research. These costs will slow or stop research. It appears that many of the new changes reflect opinions rather than actual data about what benefits animal subjects. By imposing arbitrary guidance requirements, the changes also diminish the ability of local institutions to ensure adequate welfare.


Comment 2:
Data are needed to guide policy decisions. OLAW should require institutions to comply with a new Guide no earlier than May 2015 (or three years after the date that this comment period closes, whichever comes later), in order to allow NIH and other organizations to acquire and analyze data relevant to any regulatory additions placed in the Guide.

438 04/22/2011 at 03:10:31 PM Self     Comment 1:
NO. Opposed.


439 04/22/2011 at 03:14:16 PM Organization Columbia University New York, NY Comment 1:
I oppose approval of the new guide.


Comment 2:
I oppose using the new guide for IACUC inspections.

440 04/22/2011 at 03:24:12 PM Self     Comment 1:
No. This new edition creates unnecessary and costly restraints for animal research taht will harm science and patients through impeding critical work leading to new drugs and treatments.


441 04/22/2011 at 03:29:03 PM Organization University of California, San Diego La Jolla, CA Comment 1:
The eighth edition of the Guide should not be approved. It creates unnecessary and unsubstantiated changes in animal care that will be deleterious to research activities.


442 04/22/2011 at 03:58:42 PM Self   St. Davids, PA. 19087 Comment 1:
I do not believe this 8th edition should be adopted.

It may create barriers to much-needed animal research...while significantly increasing research costs and bureaucratic obligations.


443 04/22/2011 at 04:23:52 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

444 04/22/2011 at 04:28:43 PM Self     Comment 1:
No, NIH should not adopt the eight edition formulation Guide for activities involving animals.


445 04/22/2011 at 04:41:48 PM Self     Comment 1:
MAJOR POINT: RESTRICTION IN THE USE OF EXPERIMENTAL COMPUNDS UNDER EVALUTION AS POSSIBLE THERAPEUTIC MEDICATIONS OR AS KEY RECEPTOR/CARRIER AGENTS THAT ALLOW MECHANISTIC UNDERSTANDING OF CELLS AND RODENT PHYSIOLOGY WOULD CONSIDERABLY IMPEDE FUTRE MEDICAL BENEFITS FROM ANIMAL RESEARCH


446 04/22/2011 at 05:19:04 PM Self     Comment 1:
The revised guide makes abrupt and costly changes to the care and use of laboratory animals, often without any scientific basis. Adoption of the eighth edition and implementation of plans based on that edition should be delayed while the scientific basis for changes is evaluated. Any changes determined to be justified by data should be implemented gradually to minimize the harm to already stretched budgets.


Comment 2:
The revised guide makes abrupt and costly changes to the care and use of laboratory animals, often without any scientific basis. Adoption of the eighth edition and implementation of plans based on that edition should be delayed while the scientific basis for changes is evaluated. Any changes determined to be justified by data should be implemented gradually to minimize the harm to already stretched budgets.

447 04/22/2011 at 06:57:48 PM Self     Comment 1:
No. It is unclear how the eighth edition of the Guide for the Care and Use of Laboratory Animals will benefit animal welfare. There is no clear scientific justification for the proposed policy changes, which will undoubtedly increase the cost of animal research to both individuals and institutions and will increase the amount of animals required for sound basic research.


448 04/22/2011 at 07:49:00 PM Self Univ of IL Chicago IL Comment 1:
The guideline will have mankind and fail to benefits animals.


449 04/22/2011 at 08:01:09 PM Organization University of Wisconsin-Eau Claire Eau Claire, WI Comment 1:
Do Not Adopt


Comment 2:
Do Not Adopt

450 04/22/2011 at 10:47:20 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

451 04/22/2011 at 11:43:57 PM Self     Comment 1:
Absolutely not. There is no scientific rationale. It is difficult to discern who is behind this proposal. Cage manufacturers? It's hard not to be cynical here.

This is a terrible, terrible initiative. Implementation would greatly hurt scientific research on several levels.


Comment 2:
Totally superfluous.

452 04/23/2011 at 12:28:29 AM Self     Comment 1:
There is no good substantive reason for a new guide. Just because a guide is a few years old doesn't mean it needs to be changed.


Comment 2:
2012 is unreasonable, even if there were strong reasons for a new guide. Much research would be disrupted in attempting to meet this time frame. A 4-5 year time frame would allow steady, systematic changes.

453 04/23/2011 at 07:46:22 AM Self     Comment 1:
I am AGAINST adoption of the new edition of the Guide 8th edition of the "Guide for the Care and Use of Laboratory Animals"


454 04/23/2011 at 10:34:32 AM Self     Comment 1:
NO. This new version is overly burdensome without scientific rationale. The new version was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy" without any basis. Why were no scientists consulted? Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies increase infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

455 04/23/2011 at 10:52:19 AM Organization Temple University Philadelphia, PA Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

456 04/23/2011 at 11:11:35 AM Self     Comment 1:
No


Comment 2:
OLAW should require institutionla compliance with the new Guide no sooner than March 2015 to allow for the collection of relevant data. We are scientist, so is the ata that should guide policy decisions.

457 04/23/2011 at 11:21:49 AM Self     Comment 1:
Existing regulations are more than adequate to assure humane treatment of animals. Stricter standards as proposed are unnecessary. It is inappropriate and cost ineffective to apply all the same standards to animals as a required for people.


458 04/23/2011 at 11:29:45 AM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

459 04/23/2011 at 12:27:16 PM Self     Comment 1:
I echo the concerns of my colleagues over the increased regulatory burden caused by the new version, without adequate justification.

Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions.

Most significantly, Restrictions against using animals in multiple procedures surely increases the number of animals needed. This goes in the wrong direction, in that logic would dictate that it is most ethical to reduce the numbers of animals used in research.

Mandatory requirements for new cage sizes for rodent breeding will require large expenditures, which is not adequately justified.

In summary, I recommend that the NIH not adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs.


Comment 2:
Given the concerns outlined above, an opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

460 04/23/2011 at 12:42:42 PM Self     Comment 1:
This current effort that seems largely driven by the unwarranted notion that somehow dire change is needed, while insufficient evidences are offered supporting this status, is frankly frustrating. Once again, caring scientists who treat animals with the utmost respect are being characterized unfairly in a manner opposite to the evidence. What is missing, it seems to me, is a healthy dose of reasonableness that slips right out the window once bureaucratic mandates come down on the scientific community. Already, decisions about research progress are being made for researchers by veterinarians using simplistic and presumptive rules of thumb regarding pain management, animal housing requirements, feeding restrictions, drug use, and general items of care while the contrary evidence is scoffed at. Why listen to the collected wisdom of researchers who have worked with animals in the very conditions they propose for years when presumptions can be made that seem reasonable based on whether a human being "might" be uncomfortable under similar conditions? How has the value of simply observing animals in the conditions proposed to see if any signs of distress arise been so thoroughly demoted? Mostly, the rapport that doctoral and medical practitioners once had with the veterinary staff, which used to be one of mutual support of the goals related to animal research, seems to be eroding into increasing challenges, terribly long deliberations, and the minutia of paperwork that is already having a significantly diminishing impact on research progress. This seems totally backwards. People within the business of preclinical research who we would all think would want to help promote it, are consistently disrupting it by introducing stronger arm legislation such as what is easily found throughout this document. There are obvious cases during the course of some more invasive research where social housing makes absolutely no sense. When researchers can just explain this, and reasonable people are at the helm, easy accommodations can be made. There are also other obvious cases where certain analgesics will have an interfering effect on, and easily confound, research efforts even in protocols where no evidence for pain or distress have ever arisen... but the mandate precludes reasonableness. In my humble opinion, this is going to destroy the business of saving lives or improving human lives for no good reason. No good evidence for the increased burden this document represents has been put forward, and yet we are supposed to swallow it whole. A huge impact will result on the jobs of my fellow admirable human beings who simply wish to explore the principles of health at a reasonable and permissible cost. Smaller universities will not be able to bear the burden and excellent research programs that train our Americans and bring new minds into the field of biological health will be shut down.


Comment 2:
Implementing this plan onto the backs of any institution in its current form seems to be a recipe for an unbearable burden for many smaller universities. While it may be a decision worth discussing whether to simply eliminate the smaller players, this will come at a huge cost to progress in the science of medicine. Big institutions are already concerned, at a time when grant funding is becoming increasingly challenging to procure, about the bottom line that defines whether scholarly research should be a part of the program. Shuffling of positions while trying to bear the burden of all the extra paperwork and regulation, and being forced to purchase new housing when evidence that the older housing is insufficient is incredibly weak, and other of the mandated changes are implemented will be an unwarranted slap to institutions that are currently able to contribute to this area.

461 04/23/2011 at 01:18:53 PM Self     Comment 1:
My primary reaction is that this would take us a giant step forward toward consuming so much of an investigator's time in compliance, that there will be little time left for actual conduct of the research.

As an initial comment, let me state that our IACUC already views every 'should' as a 'must' in the Guide, and that the paperwork and regulatory burden is already much higher than needed with the current Guide. I have made the statement at my institution that there have been enormous increases in paperwork burden and compliance requirements, without a single increase in actual animal welfare. I stand by this statement, and, at my institution, this would hold for the proposed new Guide.

There are a number of particulars, a few of which include:

Design considerations,which a number of older institutions cannot comply with, but IACUCs will mightily attempt to do so. At my institution, the transition zones between animal housing, animal testing, and student offices are murky, and we had a very long battle with the IACUC over whether personnel must wear booties, with many changes per day and enormous cost, when transition zones are not clear. Many older, smaller facilities, cannot comply with new requirements, which are clearly geared toward very large, centralized facilities. A net effect of the new Guide would be to drive many smaller facilities, and their investigators, out of business.

A new mandate for PPE. Availability, training, and choice should be sufficient. Many rodent researchers judge that they do not require much in the way of PPE. Under the guide, all would be required to wear what the IACUC judges.

Much more in the way of paperwork requirements, such as a disaster plan, etc.

Extension of the requirements to fish; not my issue, but for investigators with a few aquaria, this is hugely burdensome.

The issue of 'pharmaceutical grade' chemicals for use in animals. A huge number of investigational drugs are not available in this formulation, and the paperwork requirements for review would be burdensome.

Elaboration of requirements for enrichment, food/water restriction, etc.

And the list goes on. I strongly urge that the proposed Guide be scrapped, and that a new effort, not piggybacking on earlier versions and adding more restrictions, be initiated. The focus of the new version should be on actually protecting the welfare of animals, WITHOUT adding tons of additional compliance burden which does little for animal welfare. It should also differentiate MUCH more clearly between primates, for which a good bit of the current Guide may be appropriate, and species such as rodents. leaving the differentiation to an IACUC imposes primate-level requirements on rodent researchers.

As a final comment, let me give you a single example of the impact of existing guidelines and implementation. For context, I chaired our IACUC for 20 years, and I am at what has recently become a Carnegie I institution. For me, the burden of compliance has already become so great that I just announced that I am discontinuing funding efforts and leaving animal research, and that is only partly as a result of our IACUC's imposition of a three month salary fine upon me for 'unauthorized transport of a rat'. IACUCs already have [and use] the power to make life miserable for researchers and students. The improvement in animal welfare [noted above as negligible], is simply not worth the enormous investment in compliance time and associated aggravations. A likely effect of adoption of the much-expanded Guide would be to drive many researchers out of animal research.


Comment 2:
I am fine with the notion of semiannual program and facility evaluation, but I am NOT fine with using the proposed revision of the Guide as the basis for that.

462 04/23/2011 at 02:46:19 PM Self   Philadelphia, Pa Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

463 04/23/2011 at 03:17:25 PM Self     Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

464 04/23/2011 at 05:56:40 PM Self     Comment 1:
I do not think that NIH should adopt the 8th edition of the Guide because of numerous controversial items and obvious inconsistencies. Additional time is needed to allow for commentary from the scientific community and the resulting editing of the 8th edition that will result from such commentary. Just one example of the problems associated with the 8th edition of the guide are the substantial increase in costs to conduct basic research that will result. These increases will be seen on both the researcher and oversight sides of the overall research enterprise. Given the current global economic climate, oversight committees related to animal research should be trying to identify ways in which research can be done in a less expensive manner while still protecting the health and safety of the animals. Furthermore, many of the proposed changes related to repeated testing and multiple surgical procedures will result in increased animal usage which is absolutely contrary to the mission that many researchers have engaged in for their entire careers (i.e., the attempt of researchers to reduce the number of animals used while still maintaining statistical power for their data analysis).


Comment 2:
I do not think that the first inspection for which researchers will be accountable to the standards of the 8th edition of the Guide should occur by 3/31/2012. Given that researchers do not have the ability to modify their budgets to accommodate a situation, such as this, that will alter the way in which they conduct research by adding considerable expenses, I believe that if the Guide is adopted, the first inspection utilizing the Guide should not occur for at least 5 years given that the typical duration of an R01 is 5 years.

465 04/23/2011 at 08:38:42 PM Self     Comment 1:
I do not approve of the proposed revision of the Guide for the Care and Use of Animals.


466 04/23/2011 at 10:26:19 PM Self     Comment 1:
NIH should NOT adopt the eight edition.


Comment 2:
March 31, 2012 is too soon. I vote to extend it to 2015.

467 04/24/2011 at 12:39:42 AM Self     Comment 1:
I do not think it's necessary to change the Guide, Since We don't know if this increase or decrease the health and wellbeing of animals. Also I do not think it is good for the mice and the pups to change cages soon after delivery.


468 04/24/2011 at 10:08:51 AM Self     Comment 1:
I do not think it is a good idea to adopt the new Guide as policy governing federally funded research. With the new guidelines there will be an increase in the authority of local Institutional Animal Care and Use Committees, expense of research and paperwork to conduct it. Not all of these recommendations/changes are based on empirical research,they just seem to be a burden to researchers. As a student in an animal research lab this is disheartening. Currently I am learning how to apply behavioral principles in teaching a goldfish to push a soccer ball. Our school did not have an animal lab, but one ambitious professor started a lab at our school with his own money in hopes to demonstrate to the school an animal lab would be a great investment. If the new guidelines were in place, with the increase in the cost of research, this would not have been a possibility. The school is now considering providing funding for such a project! Making the guidelines to begin research too stringent would discourage animal research, which ultimately leads to human research. Have guidelines that reasonable and in the best interest to the animal.


Comment 2:
I think institutions should have more time to get ready for the changes to the guidelines. At least 3-5 years is enough time to restructure each animal lab's structure to accommodate for attending programs and facility evaluations.

469 04/24/2011 at 10:16:16 AM Self     Comment 1:
Areas of concern include: (1) the requirement to use pharmaceutical grade chemicals or justify lack of availability, when there is no clear definition of pharmaceutical grade and when most drugs used for research purposes are not available in clinical preparations (where pharmaceutical grade ratings are typically used) and, even if available, may be produced in preparations inappropriate for research use in laboratory animals; (2) major increases in research costs for inadequately justified increases in cage sizes as well as for the mandate for daily monitoring of both food and fluid of all animals receiving one or the other restriction; (3) restrictions against multiple survival surgeries that are necessary for certain types of empirical research questions (e.g., when conducting surgery to implant a replacement hormone pellet after gonadectomy, mandating the conduct of the 2 surgeries at the same time would result in inappropriate, unphysiologically high hormone levels during the initial post-surgical period). The changes provided in the Guide clearly provide additional constraints to the exercise of scientific and professional judgment of investigators and will add significantly to the paperwork burden of investigators and IACUCs. The new Guide also oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., DEA and OSHA).


Comment 2:
I concur with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document" as defined by the OMB which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more..." Therefore, a meaningful opportunity to comment is necessary before a decision on Guide adoption and implementation strategy can be made.

470 04/24/2011 at 11:03:16 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

471 04/24/2011 at 12:01:46 PM Organization ASPET Bethesda, Maryland Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

472 04/24/2011 at 12:21:12 PM Self     Comment 1:
Do NOT Adapt.


Comment 2:
Oppose.

473 04/24/2011 at 03:32:43 PM Self     Comment 1:
I could not identify the scientific justification for some of the requirements specified in the new guidelines (e.g., cage sizes, food restriction regimens, etc.). In the absence of a clear rationale for these changes, I recommend that we NOT adopt the guidelines as currently proposed.


Comment 2:
Given the broad-based nature of the changes being proposed, their associated expense AND the lack of scientific justification, I recommend that we postpone the date by which these guidlines will go into effect. If nothing else, we should try to empirically identify the best practices related to some of the contentious issues in the guidelines and that will take some time.

474 04/24/2011 at 03:38:45 PM Self     Comment 1:
I oppose adoption of the 8th edition of the Guide. Additional time is needed to revise the guidelines based on feedback from the scientific community. Implementing the 8th edition of the Guide will substantially increase the costs of conducting basic biomedical research. These increases will result from the more intricate rules and procedures proposed -- MANY OF WHICH DO NOT INCREASE ANIMAL HEALTH AND WELL-BEING -- that both researcher and already overburdened IACUC's will struggle to implement. Given the current global economic climate and the steadily climbing costs of R&D in health care, we SHOULD be determining ways in which animal research can be done more efficiently and inexpensively -- NOT THE OPPOSITE. The current Guide is more than sufficient in terms of ensuring health and well-being of animal subjects. Furthermore, many of the proposed changes related to repeated testing and multiple surgical procedures will result in INCREASED ANIMAL USAGE which is absolutely contrary to efforts to decrease the numbers of animals used in research.


Comment 2:
If the 8th edition is adopted, institutions and researchers will need at least FIVE YEARS -- not ONE -- to implement and evaluate. Unless Congress is prepared to underwrite the costs of this undertaking using American taxpayer dollars WITHIN THE NEXT YEAR (i.e., to hire more people to engage in oversight, and to support all U.S. NIH-funded researchers with supplements to their grants), it will be an exercise in futility.

475 04/24/2011 at 04:33:44 PM Organization Temple University Philadelphia, PA Comment 1:
NO.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

476 04/24/2011 at 05:41:14 PM Self   Arlington, TX Comment 1:
While endorsing the overall intentions of the proposed guidelines for the care of non-human research animals, I recommend retaining the 1996 Guide as PHS policy. The proposed guidelines will unnecessarily increase the difficulty and cost of conducting research using non-human research animals and incorporate some important and potentially costly requirements that are not based upon empirical research (e.g., re. cage size, food and liquid restriction).


Comment 2:
If the proposed 2011 guidelines are to be implemented as PHS policy, in order to allow ample time for research programs to accommodate the necessary physical plant and equipment changers and expenses, implementation should be delayed until 2015. The current financial limitations and exigencies of many research programs make allowed time beyond 2012 very important.

477 04/24/2011 at 05:41:50 PM Self     Comment 1:
There is no need for a new set of rules. This new set will simply require much more time, money and effort to do what is unnessary. There is no evidence that the changes requested will improve the state of the animals. In fine, one gets the feeling that this is all being done to interfere with ongoing research.


478 04/24/2011 at 07:13:33 PM Self University of Arkansas for Medical Sciences Little Rock, AR Comment 1:
With new NIH funding at an all-time low, and existing grants subject to substantial administrative reductions, ANY policy changes that incur new unmet costs must be exhaustively scrutinized, and must meet the HIGHEST STANDARDS of need and justification. A large and quantifiable benefit to animal welfare MUST be shown in order to justify the harm that will inevitably be done to human disease-related research. In the absence of strong scientific justification for such benefit (which is currently lacking), implementation of these proposals should be delayed indefinitely.


479 04/24/2011 at 08:55:22 PM Self   Eleva, WI Comment 1:
No. Do not adopt the 8th edition of the Guide. Retain the 1996 Guide as PHS policy.


Comment 2:
If the new policy is adopted (I do not support this), I recommend at least 4 years given the expenses involved with changes imposed by the Guide.

480 04/24/2011 at 09:09:51 PM Self     Comment 1:

I received notice that the 8th edition of the "Guide for the Care and Use of Laboratory Animals" was in consideration for adoption as policy only on April 20. When I first saw a copy of the new Guide I thought that it had been thoroughly vetted and was adopted for use. Now I find that not only is it not adopted but, in fact, I had only a few days to respond. My Easter Sunday three-day celebration was seriously interfered with in order to prepare this response to the questions you ask.

I have served on an IACUC for a total of 21 years. So I have seen changes that were accepted by the research community in order to better their research. However, there has not been such an upheaval of established procedures in these changes until now. The following are the main points of my response.

1. First, the existing draft of the 8th edition SHOULD NOT be adopted as PHS Policy in the proposed schedule. The proposed changes are so invasive but subtle that more time is needed to thoroughly comprehend the changes by researchers and digest their impact on the research community in the USA.

2. The 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies CONSTRAIN the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. These will add significantly to the cost which grants must pay and to their institutions. This comes at a time when grants are being decreased both in money and numbers.

3. Requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. We don't as yet know what these requirements are.

4. A major change in the Guide is the introduction of cautions against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research.

5. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating, "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." Thus for the first time, the Guide appears to want to step into the regulation of agricultural and invertebrate animals.

6. There are imprecise wording in this draft which needs to be straightened out before researchers are sure of the implications of this draft.

7. The Guide under consideration is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs."

8. In CONCLUSION, this version of the Guide is not ready for acceptance and SHOULD NOT be accepted. It contains many statements that are not clear for their implementation. Researchers strapped for research funds will be hard pressed to put these rules into use.


Comment 2:
The date of March 31, 2012 in entirely TOO EARLY. By that time the Guide may not be accepted and if it is, IACUCs will not have time to change their policies.

481 04/24/2011 at 09:50:18 PM Self     Comment 1:
I vote against adopting the new Guide as policy. I recommend maintaining adherence to the 1996 Guide.


Comment 2:
Given the expense of a variety of cage size and housing requirements during this time of great financial difficulty for research institutions, I recommend waiting at least 4 years (e.g., 2015).

482 04/24/2011 at 10:21:34 PM Self     Comment 1:
Do not adopt this "revised" Guide. I know other colleagues will point out specific deficiencies (and there are many), but I would like to make a larger point. I serve on multi-institutional committees, internal committees, etc., and I do have an appreciation for the necessity for rules and policies, but as a practicing scientist in a challenging financial environment, I am also sensitive to "bureaucracy creep". This adds unnecessary burdens to scientific research while yielding little to nothing to benefit animal welfare, which is already at a high standard. This is unnecessary and burdensome and should be rejected.


Comment 2:
Current procedures and guidelines are adequate. This guide does little to improve on exisiting procedures. This guide should be rejected. (e.g., "leave well enough alone")

483 04/24/2011 at 11:15:43 PM Self     Comment 1:
NO. The NIH should NOT adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals. Many of the recommendations contained in the 2011 Guide are not based on empirical scientific evidence (e.g., cage sizes, food & liquid restriction) and would seriously impede or delay progress in scientific research that will benefit the public health. In addition, most recommendations will require significant, costly alterations for institutions and investigators. For example, there is no evidence that pharmaceutical-grade drugs would improve animal welfare. Moreover, research would be impeded because commercially available pharmaceutical-grade formulations are often single concentrations that make it difficult or impossible to manipulate drug dose or to compare different vehicles. Using pharmaceutical-grade drugs will also increase the cost of pharmacological research. Some nonhuman primates live for more than 25 years, and repeated measures are often necessary to answer important research questions using longitudinal designs. Constraints on multiple procedures in animals will make such studies increasingly difficult to complete. Further, repeated surgeries are often necessary to repair or prolong the life of surgically implanted experimental devices. Decreasing the number of manipulations permitted with individual animals will increase the total number of animals used in biomedical research. Paired housing of nonhuman primates, as recommended in the 2011 Guide, would place animals at risk for injury and death. Aggression in response to any surprise (a novel noise, person, pain, etc.) may lead the dominant member of the pair to attack/kill the weaker or more submissive cage mate. Studies that require implantation of any device such as an IV catheter to evaluate medication effectiveness could not be conducted. Further, researchers using nonhuman primates go to great lengths to provide various types of "enrichment" to the animals (i.e., toys, mirrors, food, etc).


Comment 2:
Implementation of any changes to the 1996 Guide should be delayed for at least five years to allow the NIH to gather scientific evidence to support or to refute the many questionable recommendations proposed in the 2011 Guide update.

484 04/24/2011 at 11:42:11 PM Self     Comment 1:
There is not adequate justification for supplanting the 1996 Guide as PHS Policy and that there are numerous problems with the new Guide as federal policy.

The 8th edition represents a significant departure from the 7th. Although it includes much new information, it also incorporates new policies in a number of areas. Of particular concern to is the extent to which the 2011 Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians.

Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish.

Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members.

A major change in the Guide is the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures. This echos a caution in which investigators are strongly discouraged from advocating animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research.

The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. This may represent only imprecision in drafting, but is only one example of guidance that is inappropriate.

The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Although OLAW has published a similar set of statements on its website in recent years, the status as enforceable PHS Policy has been controversial due to their de novo introduction of the topic as an answer to a "Frequently Asked Question," (i.e., no previously published PHS Policy nor the Guide had addressed use of drugs in research). No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of, first, the USDA/APHIS Policy 3, an interpretive rule for use of pharmaceutical grade "medications" to prevent pain/distress in the conduct of research; and second, the NIH policy for its intramural program on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement has made clear that Policy 3 is interpreted to require use of commercially prepared solutions, rather than those prepared by investigators; the first sentence of the new Guide section on this topic is consistent with this view. Yet the NIH policy defines "pharmaceutical grade" drugs as those manufactured according to USP standards, thus accommodating the practice of preparation of drug solutions in the laboratory. Yet even that intramural NIH Policy ignores the fact that the NIDA drug supply program, which has been operating to supply compounds to funded researchers for decades, does not prepare to USP standards, because they are unnecessary for research purposes. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking. Yet, as with other sections, the contradictions in guidance were not recognized by those who published the 2011 Guide. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify their use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the intrusion of the new Guide into second-guessing scientific and professional judgment of experts in their fields of research. This represents only one of many examples of greater burdens on the IACUC, and by extension staff, imposed by new requirements.


Comment 2:
I concur with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

485 04/25/2011 at 12:00:40 AM Self     Comment 1:
No. These guidelines don't seem to have any scientific rationale, but they will really hamper research by adding a lot of administrative burden that has no benefit to the animals. These guidelines look to me like they are intended to function for the slow strangulation of animal research. Remember that we have options: Many of us can leave the U.S. and work in other countries that are becoming more conducive to research, while the U.S. is steadily making itself a less inviting place.


486 04/25/2011 at 09:06:55 AM Organization West Chester University West Chester, Pennsylvania Comment 1:
I vote AGAINST adoption.

The new Guide is nearly twice as long as the 1996 version, and contains a great deal of new policy that promises to significantly increase a) the expense of research, b) the paperwork burden on researchers, and c) the authority of local IACUCs to restrict already peer-reviewed research. And while some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food and liquid restriction). Although only federally funded research is currently at issue, because the OLAW standards set the compliance agenda for all IACUCs, it is only a matter of time before the more stringent regulatory standards trickle down to even small-scale animal research and teaching programs.


Comment 2:
Because of the extent and complexity of proposed new requirements if adoped, I recommend at least 4 years (e.g., 2015)for compliance given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

487 04/25/2011 at 09:32:04 AM Self     Comment 1:
I am AGAINST adoption of the new edition of the Guide for the Care and Use of Laboratory Animals (Guide). My objection stems from a number of new sections added to this version. Of particular concern is the extent to which the 2011 Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding) and mandatory requirements for social housing of all species (without leeway for practical constraints - animal fighting, illneess, etc.) will require large expenditures of funds to accomplish. In addition, the newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It fails to acknowledge the critical importance of collaborations by chemists with researchers to develop new therapeutic drugs or formulations. It is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Furthermore, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation. This new regulation is burdensome and expensive without benefit to animal welfare or science.


Comment 2:
Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. We currently have annual renewals, repeated training sessions, and online continuing eduation. These new policies question professional judgment and add significantly to the paperwork burden for investigators and IACUCs.

488 04/25/2011 at 09:43:30 AM Self     Comment 1:
I am writing about the changes in the "Guide" regarding husbandry for mice. The requirement it proposes to provide more space per mouse, and per dam and her litter, would be very costly. Considering the current debate over the budget in Washington this could not come at a worse time.


489 04/25/2011 at 10:10:36 AM Self     Comment 1:
There are several problems with the proposal. The most absurd change I find is a requirement to use 'pharmaceutical grade' drugs to animals. There is no evidence that the 'lesser' are harmful, and the pharmaceutical hike up the cost of doing business with little rationale. The whole regulatory process has become absurd...our good judgment is constantly usurped by some regulatory body whose intentions may be good, but whose bureaucratic execution is a nightmare, costing taxpayers much more money than need be and as a result of researcch overhead, making a serious cut in how much research ever gets funded. For what? I can't think of anything that I do today that I didn't do 25 years ago...I just get a boatload of forms to fill out, and everything cost more (oh, and I can't give my animals toys, because they can't be sterilized, or they might harm themselves playing with a ball!). I doubt if the average taxpayer would be in favor of a 'purpose-bred' anything if they knew how much it hikes the cost of animals..and for purposes that still escape me (I'd grant some Class B suppliers were not taking care of the animals...but, there's a true regulatory issue...where was the government on that one?). Instead of more regulatation, the group needs to look at the big picture. At any university, you have smart people. Lord knows, you have enough 'compliance' and 'ethics' programs to choke anyone...yet, despite this 'education', the policy is to trust nobody, and increase cost to the taxpayer in terms of research dollar, both on the grant given, and the grant that was never given because bureacracy on the grant given took money away needlessly.


Comment 2:
one per year is enough. This reminds me...One reason I came back to grad school was because I was working in a facility for the mentally 'challenged' in MA ...my 'job' was to evaluate the IQ and psychological well-being of the 'resident', and make recommendations for progress over the next year. I'd then go to a meeting with a social worker, education specialist, occupational therapist, physical therapist, and physician where we'd all make our report. These reports were 'required' and the government had funds for these reports which were nearly always the same year after year. But, nothing ever happened. Nearly none of the changes recommended were implemented, because there was no money for that ...just the 'report'.....year after year after year...

490 04/25/2011 at 10:13:33 AM Self     Comment 1:
The new edition guide should be adopted and implemented with no delay. If anything it did not go far enough regarding environmental enrichment for all species, social housing, and run size for NHP.


Comment 2:
The new edition guide should be adopted and implemented with no delay. If anything it did not go far enough regarding environmental enrichment for all species, social housing, and run size for NHP.

491 04/25/2011 at 11:07:49 AM Self     Comment 1:
I am AGAINST the adoption of the new edition of the guide.


Comment 2:
I concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

492 04/25/2011 at 11:13:39 AM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

493 04/25/2011 at 11:29:19 AM Self     Comment 1:
I do recommend that the NIH adopt the eigth edition of the Guide.


Comment 2:
I think that this timeline is acceptable as long as IACUC can accept reasonable plans for implementation. Institutions should not be required to immediately implement some of the new requirements, such as the cage requirements for breeding mice.

494 04/25/2011 at 11:39:37 AM Self     Comment 1:
Do not adopt the eight edition. It requirements will hamper scientific research with no clear benefit to animal's welfare.


495 04/25/2011 at 11:42:24 AM Self     Comment 1:
I vote against the 8th edition of the guide for care of laboratory animals.


Comment 2:
Were the changes to be accepted, I recommend at least four years delay (2015) for full compliance given that this is a time of great financial difficulty for institutions.

496 04/25/2011 at 11:55:27 AM Self West virginia University   Comment 1:
I have one comment regarding the new Guide and this relates to the avian cage sizing description. It lists 0.8 sq ft per pigeon. Pigeons escape predation by out flying predators. I note that I've seen pigeons housed for 20 years (+) where the caging does not allow normal wing use (e. g. flapping exercise or flight) although the individual housing area exceeds 0.8 sq ft. To me, flapping is a normal behavior of flighted bird species in general, and pigeons in particular. Galliformes do much more running than flying when given the choice, so the guidelines might be more applicable to them.

The USDA has a policy for bats that they be exercised in a flight to retain flying ability. While birds seem to retain their flight capabilities a bit more easily than bats, the Guide does little to explicitly address this issue. For example, the new version alludes to quality space, but provides no real guidance in this regard, especially when it is considered that a large number of birds may be used in long-term psychological studies where enrichment and group housing are disallowed for scientific reasons over months or even years. I have personally observed birds moved from smaller to larger cages become more responsive, active and to start flapping as regular exercise when adequate space is provided. For White Carneau pigeons, this is means providing at least 1 area dimension of ~30 inches. In any case, the difference in regulatory treatment between birds (PHS) and bats (USDA) seems like an inherent inconsistency for flighted species.


497 04/25/2011 at 12:24:05 PM Self     Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


498 04/25/2011 at 12:28:10 PM Self     Comment 1:
I am against the adoption of the eight edition of the Guide for the Care and Use of Laboratory Animals because its adoption will decrease the scientific impact of research related to the study of the central nervous system.


Comment 2:
I am against this proposed implementation plan.

499 04/25/2011 at 12:44:40 PM Self     Comment 1:
Although it includes much new information, the new Guide also incorporates new policies in a number of areas. Of particular concern is the extent to which the 2011 Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish. Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. A major change in the Guide is the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures. This echoes a caution in which investigators are strongly discouraged from advocating animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research. The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. This may represent only imprecision in drafting, but is only one example of guidance that is inappropriate. The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Although OLAW has published a similar set of statements on its website in recent years, the status as enforceable PHS Policy has been controversial due to their de novo introduction of the topic as an answer to a "Frequently Asked Question," (i.e., no previously published PHS Policy nor the Guide had addressed use of drugs in research). No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of, first, the USDA/APHIS Policy 3, an interpretive rule for use of pharmaceutical grade "medications" to prevent pain/distress in the conduct of research; and second, the NIH policy for its intramural program on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement has made clear that Policy 3 is interpreted to require use of commercially prepared solutions, rather than those prepared by investigators; the first sentence of the new Guide section on this topic is consistent with this view. Yet the NIH policy defines "pharmaceutical grade" drugs as those manufactured according to USP standards, thus accommodating the practice of preparation of drug solutions in the laboratory. Yet even that intramural NIH Policy ignores the fact that the NIDA drug supply program, which has been operating to supply compounds to funded researchers for decades, does not prepare to USP standards, because they are unnecessary for research purposes. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking. Yet, as with other sections, the contradictions in guidance were not recognized by those who published the 2011 Guide. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify their use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the intrusion of the new Guide into second-guessing scientific and professional judgment of experts in their fields of research. This represents only one of many examples of greater burdens on the IACUC, and by extension staff, imposed by new requirements.


Comment 2:
I concur with NABR that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.

500 04/25/2011 at 12:58:25 PM Self     Comment 1:
The idea that "human-grade" pharmaceuticals be required for animal research is not nessary, nor desirable as such a requirement will hamper, rather than promote research in addition to being expensive. I am all for improving the conditions for husbandry but sometimes keeping animals in single cages is the only way of controlling the study. The same goes for water and/or food restriction.


Comment 2:
These guidelines should be discussed much more before implementation. Thus, in my view 2012 is way too early.

501 04/25/2011 at 03:02:19 PM Self     Comment 1:
This letter is submitted in response to the National Institutes of Health's solicitation of comments concerning the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) that appeared in the Federal Register on February 24, 2011 (76 Federal Register 10379 – 80). Note that I am a Diplomate of the American College of Laboratory Animal Medicine (ACLAM) and make these comments as an individual. ACLAM is the AVMA-recognized veterinary specialty organization that represents veterinarians certified as Diplomates in laboratory animal medicine.

I acknowledges that the Guide is the premier guidance document promoting animal welfare and compliance while supporting the animal-based research community. I do not support adoption of the new Guide in its present form. I is concerned that the new space recommendations for breeding mice are not supported by scientific literature, will have little-to-no measurable benefit on animal welfare, and yet will have a significant financial impact on animal care and use programs. These costs will be passed on to the investigators or will otherwise negatively impact research output. During the pre-publication review period, several organizations including ACLAM commented that minimal cage size requirements for rodents presented in Table 3.2 of the Guide appeared to be adopted from Annex II of the European Directive with a modification. The table in Annex II stipulates that mouse cages should provide 330 cm2 for "breeding," and clarifies breeding "for a monogamous pair (inbred/outbred) or a trio (inbred)." Table 3.2 in the new Guide however, calls for a minimum of 51 in2 (330 cm2) for a female plus litter plus 15 in2 (96.7 cm2) for each additional average sized adult mouse. The clarification language present in Annex II is absent in the Guide. Consequently, standard mouse cages used by facilities throughout the US are not large enough to house some rodent pairs (male and female) and all trios (one male, 2 females) typically maintained together for breeding purposes. If language could somehow be added back to Table 3.2 in the Guide, to allow for mouse trio breeding using existing cage sizes, I would fully endorse NIH's adoption of the Guide.

In the final version an asterisk was added to Table 3.2 with the related note: "* The interpretation of this table should take into consideration the performance indices described in the text beginning on page 55." However, this edit lacks the desired clarity since the discussion on performance indices does not provide any examples of trio paradigms and concludes with a statement that reads, "space recommendations presented here….should be considered the minimum for animals housed under conditions commonly found in laboratory animal facilities". Moreover, one "frequently asked question" (FAQ) published on OLAW's website leads us to believe that the flexibility of institutions to use performance based standards to develop and implement a policy to house mice in configurations that result in less space than stipulated in the Guide is limited. Specifically, the FAQ states that, "Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non animal welfare considerations are not acceptable (http://grants.nih.gov/grants/olaw/faqs.htm#f10).

It is important to note the authors of the Guide provide no scientific justification for the increased cage size requirement and, in fact, describe as insufficient, the information that is available to delineate space and housing needs of laboratory species. Contrast this to the significant body of science supporting current breeding densities and paradigms in the US (see references below).

By implementing the mouse breeding recommendations in the Guide, PHS-assured institutions will be forced to purchase additional cages or larger cages for breeding pairs and trios, which may require the purchase of additional racks, and in many instances, the construction of additional rooms to accommodate the increases. Bedding costs will increase and the number of males used in breeding programs will also increase because one male can no longer service two females. This last point runs counter to the 3Rs approach to animal welfare.

According to data supplied to the National Association for Biomedical Research by the Laboratory Animal Breeders Association initial capital outlay to accommodate these change will cost ~500 million dollars, with annual increased operating expenses of ~150 million dollars. Alternatively, researchers would be forced to scale back breeding populations of mice, thereby limiting research.

If the Guide were adopted by the NIH, PHS-assured institutions would be forced to spend hundreds of millions of dollars to fully comply. These costs would be passed on to the investigators in the form of increased charges which would negatively impact their ability to maintain their currently level of productivity. Increasing the cost of doing animal based research without solid scientific evidence that such increases are needed or will benefit animal welfare is not consistent with the NIH's goal "to expand the knowledge base in medical and associated sciences in order to enhance the Nation's economic well-being and ensure a continued high return on the public investment in research."

References

J Whitaker, SS Moy, V Godfrey, J Nielsen. Effects of cage size and enrichment on reproductive performance and behavior in C57BL/6Tac mice. Lab Animal, 2009.

Laber K, Veatch L, Lopez M, Lathers D. The Impact of Housing Density on Weight Gain, Immune Function, Behavior, and Plasma Corticosterone Levels in BALB/c and C57Bl/6 Mice." JAALAS, 2008. 47(2): 16-23.

O'Malley J, Dambrosia JM, Davis JA. Effect of housing density on reproductive parameters and corticosteron levels in nursing mice. J Am Assoc Lab Anim Sci., 2008. Mar;47(2): 9-15.

J Whitaker, SS Moy, BR Saville, V Godfrey. The effect of cage size on reproductive performance and behavior of C57BL/6 mice. Lab Animal, 2007

Smith, AL, et al. Effects of housing density and cage floor space on three strains of young adult inbred mice. Comp Med, 2005. Aug 55(4): 368-76.

Smith, AL, et al. Effects of housing density and cage floor space on C57BL/6J mice. Comp Med, 2004. Dec 54(6): 656-63.

McGlone et al. Floor space needs for laboratory mice: BALB/cJ males or females in solid-bottom cages with bedding. Contemporary Topics, 2001.

C. K. Reeb-Whitaker, B. Paigen, W. G. Beamer, R. T. Bronson, G. A. Churchill, I. B. Schweitzer & D. D. Myers. The impact of reduced frequency of cage changes on the health of mice housed in ventilated cages. Laboratory Animals, 2001. (35): 58-73.

Eveleigh JR. Murine cage density: cage ammonia levels during the reproductive performance of an inbred strain and two outbred stocks of monogamous breeding pairs of mice. Lab Anim., 1993 Apr; 27(2): 156-60


502 04/25/2011 at 03:18:44 PM Self     Comment 1:
No- NIH should not adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals. There is a lack of empirical data to indicate that these new regulations will enhance animal welfare.


503 04/25/2011 at 03:38:56 PM Self     Comment 1:
NIH should not adopt the 8th edition of the Guide and should strongly recommend that the Guide, as it now stands, be fully reconsidered.


Comment 2:
All implementation plans should be stopped until a number of provisions in the new guide can be reconsidered. It should not be adopted in its presnt form.

504 04/25/2011 at 03:47:35 PM Self     Comment 1:
This new version of the Guide absolutely should not be adopted. Many changes from the previous version are substantial, prohibitive and completely unjustified. As one example the required use of pharmaceutical grade chemicals is based on nothing, is completely unnecessary, will stifle science, will end careers because of undue burden, and will eventually cost peoples' lives. Additional restrictions on mild food restriction are similarly without reasonable basis and read like they were written by a bureaucrat who doesn't understand the purpose and benefit of basic scientific research. More study and justification are necessary before the new rules in the new Guide are adopted, and frankly they should never be.


Comment 2:
It seems to me that OLAW should allow a minimum of four more years for institutional compliance with the new Guide to allow for the collection of relevant data (see comment 1).

505 04/25/2011 at 03:51:15 PM Organization University of Utah Salt Lake City, UT Comment 1:
No it should not. It is not clear what the basis is for the extensive list of revisions made in this Guide. As per the report (NOT-OD-07-016) issued by the working group convened in 2006 to evaluate public comment in reply to the request (NOT-OD-06-011) for such comment on updating the animal welfare standards in the guide. Given the recommendations of that working group (NOT-OD-07-016), the justification for the extensive revisions made in the current Guide is unfounded.

In addition to making changes/revisions beyond those put forth by the working group as reflecting the public comment submitted at that time, the new Guide clearly goes beyond the traditional role of the Guide to serve as that--a guide for institutions, verterinarians, and scientific investigators to use to promote animal welfare. Rather, it contains new policies and requirements that will necessitate considerable burdens in terms of financial and paperwork requirements and restrictions on research design and the exercise of scientific judgement on the part of federally supported investigators and institutions. These burdens are being put in place with absolutely no apparent documentation supporting the contention that implementation of such policies will promote animal welfare.


Comment 2:
First, as noted above, the 8th edition as currently written should NOT be adopted for the reasons noted above.

However, if it is adopted, given the considerable financial and paperwork burden it will impose on individual investigators and institutions, the date for required institutional compliance should be NO EARLIER than March, 2015. In the meantime, data supporting the policy revisions to be required should be collected by the NIH to justify the proposed changes.

506 04/25/2011 at 04:35:40 PM Self     Comment 1:
As per request, I hereby submit my comments on the proposed Adoption and Implementation of the Guide for the Care and Use of Laboratory Animals: Eighth Edition

First of all, let me state that the Guide for the Care and Use of Laboratory Animals is an excellent document that serves as a very useful resource to use when communicating to the facilities management personnel as to what requirements we have for our animal program. It is concise and effective as a communication tool and has served us well in the past.

However, one of the changes in the Guide will cause significant economic hardship to our research program if implemented. Our animal facility has recently purchased a very large number of racks and cages for a recently expanded facility. We have an active mouse breeding program with dozens of different strains of transgenic mice. Many of the mice are difficult to breed because of sub-optimal maternal skills in the breeders. Despite the difficulties in producing sufficient litters of pups from these lines of mice, we have managed to keep our program operating through the careful monitoring of breeding trios. Once pregnancies have been established, we find that fecundity is increased by leaving both mothers with pups together in the same cage until it is time to wean the litters. When one mother exhibits poor/aberrant nursing behavior the other frequently will supply the necessary intervention to properly raise the pups. In the Environment, Housing and Management section of the guide on page 57 TABLE 3.2, Recommended Minimum Space for Commonly Used Laboratory Rodents Housed in Groups states that Female+Litter space requirements are 51 in² floor space per Female+Litter. Therefore, under the new guidelines our rodent cages would need to have 102 in² bottoms to house two litters. Unfortunately our new rodent cages only have 78 in² bottoms which are more than sufficient to house five adult mice. Our animal care staff is very good about performing extra cage changes to prevent any cage sanitation issues, and this SOP is a very important part of our breeding program. I would hate to have a requirement in the guide that would be detrimental to our breeding program by requiring us to house only one litter per cage, but I can't see us purchasing new cage racks and cages just because we are a few square inches short of what has been "suggested" as appropriate in the guide. I am quite certain that there are many other institutions that have the same caging that we use and so this will be a big issue for many facilities. Perhaps the wording could be changed to allow for additional operational controls such as more frequent cage changes be an acceptable alternative? As our accrediting agencies will expect us to adhere to the standards as set forth in the guide, these considerations are very important to us.


Comment 2:
If the restrictions on minimum space allocation for rodent breeding are addressed as outlined in the comments above, I would have no problem with implementing the guide by March 31, 2012. If the restrictions stand as is, we would be unable to meet this deadline.

507 04/25/2011 at 04:56:16 PM Organization University of Utah Salt Lake City, UT Comment 1:
NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

508 04/25/2011 at 06:26:09 PM Self     Comment 1:
I understand that one proposal is to mandate the use of pharmaceutical-grade chemicals ("when available, for all animal-related procedures") and that use of non-pharmaceutical-grade substances would need to be described and justified in IACUC protocols. I wonder if this is advantageous given the limited evidence that using pharmaceutical grade drugs would improve animal welfare or science. In addition adjustment of dose could be problematic since pharmaceutical grade drugs are single concentration formulations.


509 04/26/2011 at 10:48:52 AM Self     Comment 1:
Given the many and significant changes in the Guide, I believe it is premature to adopt this 8th edition without more opportunity for consideration, comment and revision. I am a former member of ILAR Council and have served on a variety of ILAR committees, including the committee that produced the 1996 Guide. Accordingly, I have both experience and perspective on this matter. Rather than a set of guidelines, the 8th edition is highly prescriptive with significantly increased directives that will increase the burden on researchers, IACUCs and animal care staff and administration without evidence that animal welfare will be improved. I am very disappointed in this ILAR product, which seems to have ignored the principle of evidence as a basis for moving forward.


Comment 2:
The changes, directives and significantly increased "should" and "must" in the new Guide make it unreasonable to implement it without further comment and consideration, which will certainly not be completed in a timely and careful way any too soon. In my opinion, because of the many new 'required' changes and including imposition of engineering standards for new cage sizes,the current Guide should be the basis of continuing oversight rather than implementing a flawed and imperfect new Guide.

510 04/26/2011 at 11:11:40 AM Self     Comment 1:
I vote against adopting the new guide as policy, and would rather maintain adherence to the 1996 guide. Many of the new proposed guidelines, in my opinion, will increase the expense of already costly research, add to the paperwork burden placed on researchers, and restrict scientific creativity by giving more authority to local IACUCs on already peer-reviewed research. I am dissatisfied with the recommendations that are not empirically based such as cage sizes, food and liquid restrictions.


Comment 2:
I would recommend at least four years, given the expense of a variety of cage size and housing requirements at a time of great financial difficult for research institutions.

511 04/26/2011 at 11:12:55 AM Self     Comment 1:
Please DO NOT ADOPT this guide until it has been: (1) streamlined and (2) vetted to ensure that it fairly balances the need for protection of laboratory animals with the need to minimize paperwork and burden on research institutions, particularly smaller regional and local Universities.


Comment 2:
DO NOT require programs to use this updated version until it has been streamlined and represents an IMPROVEMENT over the current Guide. Let's ensure that this is a step forward for all parties rather than adding another chunk of paperwork.

512 04/26/2011 at 11:22:45 AM Self Savannah State University Savannah, GA Comment 1:
I vote against adopting the new Guide as policy. Please maintain adherence to the 1996.


Comment 2:
I am in favor recommending at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

513 04/26/2011 at 11:24:15 AM Self California State University, Los Angeles Los Angeles, CA Comment 1:
I am opposed to adopting the eighth edition of the Guide and recommend retaining the 1996 policy.


Comment 2:
If adopted I would recommend extended the compliance date to march, 2015.

514 04/26/2011 at 11:27:24 AM Self     Comment 1:
It appears to me that the proposed guidelines will markedly increase the cost of research without improving the treatment of animals used in research. I recommend that the 1996 "Care and Use" guide be retained as the basis for evaluation of institutional programs.


515 04/26/2011 at 11:38:49 AM Self     Comment 1:
I vote against adopting the new guide as policy.


Comment 2:
The deadline for full compliance that is proposed in the Federal Register is March 31, 2012. I recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

516 04/26/2011 at 11:44:48 AM Organization Central Washington Unviersity Ellensburg, WA Comment 1:
As a scientist I applaud the efforts to maintain the highest levels of care for animals in research. There are a number of specific concerns, however, with the latest version of the Guide. To begin with, the new Guide is nearly twice as long as the 1996 version, and contains a great deal of new policy that promises to significantly increase a) the expense of research, b) the paperwork burden on researchers, and c) the authority of local IACUCs to restrict already peer-reviewed research. And while some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food and liquid restriction). Although only federally funded research is currently at issue, because the OLAW standards set the compliance agenda for all IACUCs, it is only a matter of time before the more stringent regulatory standards trickle down to even small-scale animal research and teaching programs. It is for these reasons that I vote against adopting the new Guide as policy.


Comment 2:
I recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

517 04/26/2011 at 12:50:57 PM Self     Comment 1:
I vote against adopting the eighth edition of the "Guide for Care and Use of Laboratory Animals" as policy.


Comment 2:
If the 2011 Guide is adopted as PHS policy, I recommend that at the deadline be at least 4 years (2015) for compliance by research institutions to the new policy.

518 04/26/2011 at 01:34:37 PM Self OHSU Portland, Oregon Comment 1:
As this will directly affect the already hard to pay animal costs for biomedical research, more time is needed to obtain quality input as to which guidelines might need to be updated if any.


Comment 2:
Before a more thorough interaction has taken place with all involved parties, it seems premature to incorporate recommendations as basis of new guidelines. Again, if the end result is simply even higher per diem costs it will harm the public who is benefitting from this research as well as the biomedical researchers and the institutes they work at.

519 04/26/2011 at 01:40:39 PM Self     Comment 1:
vote against adopting the new Guide as policy


Comment 2:
recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

520 04/26/2011 at 03:50:00 PM Self     Comment 1:
The newly added Guide requirement to use pharmaceutical grade drugs in research involving rodents is neither necessary nor practical, in part, because the definition of "pharmaceutical grade" is not provided. Further and more importantly, appropriate measures (e.g., the use of sterile saline or other vehicles, filtering drug solutions where appropriate, etc.) are already utilized routinely by laboratories, and I am not aware of any data demonstrating that such procedures lead to negative consequences. For this and many other reasons (e.g., including the new requirements for cage sizes), I recommend NOT approving the proposed update of the Guide.


Comment 2:
This procedure would provide an unnecessary burden on the researchers and institutions. This, I recommend NOT approving this implementation plan.

521 04/26/2011 at 11:58:02 PM Self     Comment 1:
No. Many changes in the new "Guide" will increase paperwork and expense to investigators, but have no scientifically demonstrated enhancement of animal welfare.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data.

522 04/27/2011 at 07:34:18 AM Self University of Maryland School of Medicine Baltimore Maryland Comment 1:
Adopting the Guide, will slow medical research and make advances in critical disease research prohibitive. Current grant funding is significantly low. In addition, NIH investigator grants are being cut and therefore budgets are going to be even tighter. The current rules are more than adeque at ensuring animal welfare and its is unclear how the new rules will improve them.


523 04/27/2011 at 10:37:42 AM Self     Comment 1:
The inhumane practice of some (not all) animal research laboratories is a well-kept secret in the scientific field. The fact that NIH recognizes the need for improvements in how research animals are treated is a step in the right direction. My colleagues and I in my clinical research laboratory applaud these NIH efforts and the team of investigators who are pushing for the reform of humane animal care.

Please adopt the new guidelines to protect the innocent and valuable species contributing to the clinical care of our patient populations. To degrade their quality of life by providing inhumane living conditions is a degradation of our position as a humane society and a shame for all of research.


Comment 2:
Please adopt the new guidelines.

524 04/27/2011 at 11:00:48 AM Self     Comment 1:
The new guidelines should NOT be accepted.

I am a psychopharmacologist and neurotoxicologist who has been working with the behavioral effects of drugs and toxic substances for 25 years.

The new requirement that pharmaceutical grade drugs be used, even for rodents, will impose greater costs, less flexibility, and more paperwork. It will be all cost with no benefit. I have been preparing clean, but not sterile, drug solutions for rodents for over 25 years and have never had an infection due to drug administration. The costs of pharmaceutical grade drugs from vendors is exorbitant. Preparing them in house will require additional expense and time, which would be fine if it actually did some good but, with animals whose resistance to infection is high this is completely unnecessary.


Comment 2:
Second, I am concerned about the new rigid requirements for caloric restriction. My concerns are two fold. First, the paperwork requirements will impose additional burden on many investigators, especially those in small institutions. Their work is valuable and should not be discouraged.

Second,however, is that food or caloric restriction should not be viewed as an exception but rather as the rule. As the new manual notes, rodents on ad lib diets become exceptionally obese, making them unhealthy and poor biomedical models. The guide should do all that it can to make control over caloric intake easy to do and should push for its becoming the norm.

525 04/27/2011 at 11:15:59 AM Self     Comment 1:
No--I recommend that NIH not adopt the New Guide.

My rationale for this recommendation is based on multiple factors that include:

-the financial and administrative cost of complying with new regulations and the resulting disruption in research

-the burden of guidance to either use pharmaceutical grade chemicals or to justify not using them, despite a lack of evidence to suggest that pharmaceutical grade chemicals improve animal welfare or science

-vague language subject to multiple interpretations on many issues such cage sizes, use of restraint, and use of food restriction


Comment 2:
Implementation should be delayed until at least March 2015.

My rationale for this recommendation is based on my view of the extensive revisions promulgated by the New Guide and the extensive changes in research procedures, administrative procedures and infrastructure that will be required to comply with the New Guide.

526 04/27/2011 at 04:40:58 PM Self     Comment 1:
NO


527 04/27/2011 at 05:37:09 PM Organization University of Hawaii, Laboratory Animal Service Honolulu, HI Comment 1:
The requirements for housing rat mothers with litter will impact our institution. New larger cages and racks to hold them will need to be purchased. The requirements for housing female mice with litters will also impact our researchers due to the limitations of the current floor space in the IVC cages. The mice and rats have been doing well under the current housing conditions, therefore these new requirements will have a detrimental economic effect if caging/racks need to be re-purchased.


528 04/27/2011 at 05:56:55 PM Self     Comment 1:
1. Please allow harem breeding: At our institution we are only allowed one male and one female in a mating cage. This is highly inefficient and costly, limiting production of pups. There is no harm in having two moms and litters in a cage.

2. increase the maximum number of mice per cage to 6.

It is extremely costly to do mouse work and the rising costs and limited space are pushing investigators away from this important work.


529 04/27/2011 at 10:11:01 PM Self     Comment 1:
I urge you to vote against adopting the 2010 Guide as PHS policy, maintaining adherence to the 1996 Guide. The 2010 Guide can significantly increase the financial burden of animal research for small-scale animal research and teaching programs. These small programs are essential for promoting and providing a broader range of trainees access to basic bio-social research—especially with access to training in research methods in this area.

If you feel compelled to adopt the guide because there currently are no guidelines for aquatic species, then identify the 2010 guide as the authority for aquatic species specifically, and exempt other species at this time.


Comment 2:
In the event the 2010 guide is adopted, provide researchers at least 4 years (e.g., 2015) to come into compliance given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

NIH should develop instrumentation grant programs to assist facilities in meeting any new guidelines. Of particular importance is funding to maintain teaching programs. It is impractical for educational institutions to charge students laboratory fees of sufficient magnitude to recoup the costs for upgrading equipment and related practices.

530 04/28/2011 at 02:29:30 AM Organization Cascades Biosciences Consultants, Inc Sisters, Oregon Comment 1:
The eighth Guide adds unnecessary administrative burdens, regulatory compliances, and substantial capital costs for caging of rabbits, breeder rodents, and primates. The seventh edition of the Guide has proven well in advancing animal care, welfare, and support for animals in research. Edition 8 falls short on concrete evidence of improving animal welfare. It discourages investigators who are dedicated with improving animal welfare and advancement in science. An economic impact document is needed The Guide is a USA regulatory document since it is cited by the US Public Health Service Policy authorized by HHS Law. In this sense, a legitimate question is raised as why 4 of the 14 ILAR committee members were not US Citizens.


Comment 2:
The 8th edition must not be adopted. In essence, a new committee is needed if an 8th edition is deemed necessary by the Institutes of Medicine, NAS.

531 04/28/2011 at 11:05:11 AM Self     Comment 1:
I think that revision of the guide is not necessary, and that implementation would add a great regulatory burden for IACUC and laboratory animal veterinary staff, when we are in a period of funding restriction. I am opposed to revision of the guide, and I believe that the new guide should NOT be adopted.


532 04/28/2011 at 08:49:33 PM Self     Comment 1:
I am very much against the expanded space requirements for a mouse breeding trio plus progeny. THis added requirement will force us to remove one of the two males which will significantly prolong the period between new births and render the cost of breeding our mice much higher. I also do not approve of the prohibition on including space occupied by nesting material in the total space requirements for mice. This may be OK for pigs and dogs, but mice need the nesting material to keep warm and seclude themselves.


533 04/28/2011 at 09:29:44 PM Self     Comment 1:
O.The new guide was originally supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures.


Comment 2:
OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

534 04/29/2011 at 11:43:51 AM Organization Biotechnology Industry Organization Washington, DC Comment 1:
April 29, 2011

Dr. Francis Collins Director, National Institutes of Health Bethesda, MD 20892 (submitted electronically)

Dear Dr. Collins,

The Biotechnology Industry Organization (BIO) appreciates the opportunity to provide input on the NIH's adoption of the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service (PHS) support for activities involving animals. BIO represents 1,100 member organizations that research, develop, and produce innovative health care, agricultural, industrial, and environmental technologies. Our members depend on accurate research as a part of the discovery and development of these technologies. In order to model diseases, find treatments, and perform translational research, many of our companies utilize animals in their research. The proper care and use of research animals is a high priority for our members.

Though research with rodent models continues to provide useful information, grasping a more complete fundamental understanding of specific biological questions and translating the knowledge gained to improve both animal and human health and reproduction require the use of models that more closely resemble each other developmentally and physiologically or that exhibit similar susceptibility to common zoonotic pathogens. As treatments become closer to use in humans, even more complex models are necessary to test these hypotheses. The use of domestic agricultural species to address priority research areas of high impact to biomedicine and agriculture allows a more thorough characterization of research findings. The areas of investigation and experimental approaches may involve the generation of animals that model human diseases, elucidation of the etiology involved in disease or transmission of pathogens, a determination of environmental insults underlying developmental or epigenetic changes leading to pathophysiology, metabolic studies focused on obesity, or the identification of diagnostic tools (genetic markers, biomarkers, or antibodies). This research effort is expected to deepen the fundamental knowledge of biological mechanisms essential to both humans and farm animals, highlight the utility of domestic agricultural animals as more appropriate animal models for specific mechanistic studies, and encourage investigators with farm animal expertise to be involved in research benefiting both agriculture and biomedicine. The use of these more complex models requires animal care that expands beyond that which is required for rats and mice.

Reviews of the Institute for Laboratory Animal Research (ILAR) "Guide for the Care and Use of Laboratory Animals" (the "ILAR Guide") provided to us demonstrate the ILAR Guide needs to be enhanced in order to properly accommodate the use of these other species. The ILAR Guide currently contains few items related to farm animal care and treatment, and we are concerned the stringent use of the ILAR Guide as drafted could yield the unintended consequence of negatively impacting farm animal welfare. A review of the ILAR Guide recommendations by scientists trained specifically in farm animal welfare has revealed several examples of recommendations for space allotment, temperature control, and animal management that are not in line with scientifically reviewed literature in the area. A more thorough review of the literature would have allowed the ILAR Guide to recommend measures that more appropriately addressed the needs of the animals, which do not vary whether the animal is in a biomedical or an agricultural research study.

In January 2010, the Federation of Animal Science Societies (FASS) published an updated Guide for the Care and Use of Agricultural Animals in Teaching and Research (Ag Guide). This document was written by 64 professionals with expertise in farm animal care and contains a wealth of substantive technical information about the care of farm animals in teaching or research (agricultural or biomedical). The Ag Guide was originally developed to ensure a single science-based source for the most appropriate, tested, and pragmatic protocols for the care, treatment, handling, and housing of farm animals used in agricultural and biomedical research. It was written to ensure scientists in biomedical research would have the best available information. The Ag Guide utilizes scientific literature to identify care conditions for each individual farm animal species, while the ILAR Guide is deficient in these individual husbandry requirements. The use of animals in research from PHS grants can be enhanced through incorporation of the Ag Guide's recommendations and use of the Ag Guide as the primary, if not sole, reference, for farm animal care.

Other associations have realized the value of utilizing experts in a species-specific field of animal welfare when providing guidelines for animal use and care. The Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) has decided to utilize multiple animal care and use guides as its standards. AAALAC states that, "During the Fall (September through November) 2011 trimester, AAALAC International's Council on Accreditation will begin to use three primary standards to evaluate animal care and use programs: the 8th Edition of the Guide for the Care and Use of Laboratory Animals (Guide), NRC 2011; the Guide for the Care and Use of Agricultural Animals in Research and Teaching (Ag Guide), FASS 2010; and the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, Council of Europe (ETS 123). The Council on Accreditation has used all three documents for several years and their adoption by AAALAC's Board of Trustees as primary standards signifies the importance of these performance based guidelines in the accreditation process."

We recommend that the PHS not accept the ILAR Guide as the sole basis for evaluation of programs receiving Public Health Service funded support for agricultural animals in research. We support the use of animals in research, and want to ensure their proper care through the use of best techniques from scientifically-reviewed animal welfare expert research.

Sincerely, Biotechnology Industry Organization


Comment 2:
no comment

535 04/29/2011 at 02:26:16 PM Organization University of Utah Salt Lake City, Utah Comment 1:
NO


536 04/29/2011 at 08:27:48 PM Self     Comment 1:
I am registering strong opposition against the proposed revision of the Guide, for the following reasons:

1. The revised Guide will have major negative impact upon the NIH-funded research by enormously increasing costs and administrative burdens and reducing availability of animal holding space across the U.S. WITHOUT ANY SCIENTIFICALLY BASED BENEFIT TO THE ANIMAL WELFARE. 2. The revised guide will reduce the efficacy of animal breeding and will potentially lead to deaths of many of the newborn mice because it prohibits duo and trio breeding, despite the fact that this arrangement, currently recommended in the 7th edition of the Guide, has been shown to be the most conducive to litter survival and animal welfare. 3. The new restrictive policy is inconsistent with data from multiple peer-reviewed publications evaluating the effects of cage density. Data in peer-reviewed papers published since the 7th edition show that a number of common mouse strains can be housed at twice the density recommended by 7th edition of the Guide, in some cases with apparent benefits to health. Therefore, it is troubling from both animal health and financial perspectives that maximum recommended caging densities were not relaxed to reflect this new information. 4. The new guide has not been vetted by the scientific community it is meant to serve. In too many cases changes have been mandated without scientific justification, and in many cases new scientific information has been ignored. And too often, the new Guide makes generalizations and creates ambiguities both in lines of responsibility and logical application to specific laboratory organisms.


Comment 2:
In concert with the above comments, neither the Guide nor the facility evaluation recommendations should be adopted.

537 05/01/2011 at 09:03:39 PM Self   Chicago, IL Comment 1:
This letter is submitted in response to the National Institutes of Health's solicitation of comments concerning the Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) that appeared in the Federal Register on February 24, 2011 ((78 Federal Register 10279-80.

As a clinical veterinarian with 14 years of experience "in the trenches" and on the front line to improve animal welfare in biomedical research, I strongly encourage OLAW to reject the recommendations for mouse breeding cages outlined in the Eighth Edition of the Guide. The Guide recommends 51 square inches for a single female mouse and her litter. When factoring in the requirements for the male (15 square inches), the total space requirement would be 66 square inches. The floor of a standard micro isolator cage at our facility is 66 square inches. These recommendations, if endorsed by OLAW would commit PHS-funded institutions to follow a monogamous pair breeding scheme for mice. There are major reasons why OLAW should reject this recommendation.

I am sure that OLAW has received numerous comments from directors and managers describing how adoption of these changes will impose insurmountable costs to already financially stressed animal care programs. For example, to move from our current occupancy guidelines for mouse breeding cages which alllows for trio (1 male: 2 females) to monogamous (1 male: 1 female) breeding, we would literally need to double the number of breeding cages to maintain the same number of mice. We, as well as other institutions, do not have the finances or space to support these changes.

These changes will negatively impact investigators who must breed genetically engineered mice to support their PHS-funded research programs. The investigators I have communicated with are seriously concerned about the proposed changes. Their concerns are that their budgets will not allow for it and many of their mice will not breed well as monogamous pairs. As scientists, they want to know what the scientific justification is for such dramatic changes. Unfortunately, there is no scientific justification to support the change to monogamous breeding of mice. It should be noted that the Jackson Laboratory, the number one vendor of genetically engineered mice, recommends that investigators breed their genetically engineered mice as trios. One reason for this is that breeding is a social activity in mice, and their extensive data on mouse breeding shows optimal breeding indices when mice are bred as trios. Another reason Jackson recommends trio breeding is that many mutant mice do not lactate well. Finally, the majority of mutant mice have smaller litters than outbred and even inbred strains of mice. Not only is the number of mice per litter smaller, but the mice themselves are smaller, and therefore take less space. As a result, trio breeding of genetically engineered mice does not result in overcrowding or unsanitary cage conditions.

I urge OLAW to consider the negative impact these changes will have on animal welfare. In the wild, mice breed in single male: multiple female arrangements. It would make sense for the Guide to provide to provide recommendations to breed mice in a way that most closely mimics their natural history within the confines of the laboratory mouse cage. OLAW must consider how adopting the recommendations for mouse breeding cages outlined in the Eighth of the Guide will negatively impact not only the ability of institutions to support and investigators to perform quality research, but also the breeding performance and welfare of the laboratory mouse.


538 05/02/2011 at 11:04:12 AM Self   Grand Forks, ND 58201 Comment 1:
Please do NOT adopt the eighth addition of the Guide. The new guide ignores scientific literature on rodent behavior and group structure. The animals are 'happier' and display more normal behaviors when housed in larger groups than when housed with one or two other animals.