Office of Laboratory Animal Welfare
Compliance at the Institutional and Programmatic Level
|From: Lab Animal 23(8):28-29,1994
By Axel V. Wolff, MS, DVM and Paul D. Smith PhD
At the time this article was published the authors, Axel V. Wolff, MS, DVM and
Paul D. Smith PhD, were affiliated with the Animal Welfare Division of the office of Protection from Research Risks.
The Animal Welfare Division of OPRR was renamed Office of Laboratory Animal Welfare (OLAW) in 2000. Axel Wolff is now Senior Assurance Officer, Division of Assurances, Office of
Laboratory Animal Welfare, NIH.
Although this commentary focuses on institutions funded through the Public
Health Service (PHS), it is generally applicable to all institutions because
PHS policy requires institutions to comply with the Animal Welfare Act and other
Federal statutes and regulations relating to animals. The PHS policy does not
affect those state or local laws or regulations which impose more stringent
standards for the care and use of laboratory animals. Animal facilities not
supported by the PHS come under USDA jurisdiction, follow the regulations outlined
in the Animal Welfare Act, and are administered thorough the Animal and Plant
Health Inspection Service (APHIS) via the Regulatory Enforcement and Animal
Care Unit (REAC).
Institutions achieve compliance through the assurance statement filed with
The Office for Protection from Research Risks (OPRR). OPRR is responsible for
implementation and interpretation of PHS Policy, negotiating Animal Welfare
assurances, and evaluating compliance. The Institutional Animal Care and
Use Committee (IACUC) performs a critical element of assuring compliance by
evaluating, at least semi-annually, the institution’s animal program and the
facilities used in supporting the research. The evaluation must describe the
institution’s adherence to the Guide for the Care and Use of Laboratory Animals
(Guide), identify and provide reasons for any departures from the Guide,
distinguish significant (i.e., one that may be a threat to the health
or safety of the animal) and minor deficiencies, and provide a plan and schedule
for correcting the deficiencies. The report is submitted to the institutional
official responsible for implementing the provisions of the Animal Welfare Act
and PHS Policy.
The IACUC may not exclude any member from participating in any aspect of an
evaluation, and it may use subcommittees of no less than two members. The report
must be signed by a majority of the members and must include any minority views.
The IACUC must address such issues as: the institution’s commitment to supporting
an accreditable animal program; the organizational structure and staff in place
to support the research; the mechanisms in place for addressing the human health
needs of the employees; the training programs available to scientists, animal
technicians, and other personnel involved with animal care, treatment, and use;
the procedures established for routine daily operations; the mechanisms available
for reporting irregularities; and other aspects of the animal program. All facilities
used for holding animals and all animal procedure space must be inspected for
compliance with the standards established in the Guide, PHS policy,
and the Animal Welfare Act. The report must include a reasonable and specific
plan and schedule with dates for correcting any deficiency. If the institution
fails to adhere to the plan and schedule, the IACUC must report in writing within
15 business days through the institutional official to OPRR and any federal
agency funding that activity.
The IACUC is authorized to suspend any activity involving animals if it determines
that the activity is not being conducted in accordance with the previously approved
animal study proposal, provisions of the Animal Welfare Act, PHS Policy, the
Guide, or the institution’s assurance. Usually, the IACUC will initiate
suspension of an activity and report through the institutional official to OPRR.
The Animal Study Proposal (ASP) is the first official step a principal investigator
takes to initiate an animal study, and it is usually the first interaction with
the IACUC. Reviewing ASPs is one of the IACUC’s mandates, and it allows assurance
of numerous compliance issues such as humane animal use, suitability of facilities,
training qualifications, etc. We will discuss the items which a typical
ASP should address using the standard NIH form (see reference NIH 3040-2).
The first section deals with administrative data that encompasses information
such as the principal investigator’s name, address, title of the project, and
names of all individuals who will be conducting animal procedures. The animal
requirements (species, sex, numbers of animals to be used) follow, allowing
inquiry into one of the “three Rs,” reduction in the number of animals used
The next section deals with transportation of animals, and if deliveries
from commercial vendors are involved, the IACUC can assess Animal Welfare Act
shipping regulation compliance. In the section outlining study objectives, the
investigator explains the purpose of the study and the necessity for animal
use. The other “Rs”—refinement and replacement—can be addressed here. A description
of the experimental design and the actual procedures performed follows, and is
probably the most important description used by the IACUC to assess actual care
and use. The investigator must address very specific issues including: what
types of inoculations are given; how animals are restrained; whether the animal
will experience pain or discomfort; and the experimental endpoint. In this
vein, the next section specifically addresses the details of survival surgery
and ascertains the surgeon’s qualifications, adherence to the Guide, and
the performance of multiple major procedures.
In a separate category, the investigator must again address pain or distress
by placing study animals in the USDA pain categories (C=minimal or no pain,
D=pain relieved by appropriate measures, E=unrelieved pain) and give the numbers
of animals in each column over the course of the year. This information is specifically
reported to USDA in the yearly report, and at this point the principal investigator
attaches additional justification for any Column E studies.
The next section covers in detail the types and amounts of anesthetics,
analgesics, and tranquilizers used during the course of the study to alleviate
pain and distress. The veterinary representative on the IACUC can determine
appropriateness of the drug for the species studied. A separate section deals
with euthanasia, and comparison with the most recent AVMA Panel on Euthanasia
guidelines determines the appropriateness of the method.
The investigator addresses compliance with related non-animal regulations in
the hazardous agent or biosafety section. Here, questions regarding radioisotopes,
biohazards, dangerous chemicals or drugs, recombinant DNA, and biosafety level
are examined. The institutional safety official determines the application of
the various guidelines for these agents to the study. Another small section addresses the question of
passing biological material through rodent species and whether rodent pathogens
Finally, the signatures of the principal investigator, laboratory chief, IACUC
chairperson, and others affirm the institution’s commitment to the provisions
of the Animal Welfare Assurance statement and PHS policy. In this last section,
the principal investigator, in accord with PHS policy: certifies attendance
at a training course on animal investigation and that staff have been adequately
trained in animal handling and use of proper techniques; states that a literature
search was conducted to determine if alternative procedures exist for Column
D and E studies; and, finally, promises to inform the IACUC of any proposed
significant changes in the study.
By means of the ASP document, the IACUC can assess the effect of the study
on the well-being of the research animals and receives assurances from the investigator
that all applicable rules and regulations will be followed. During review of
the document, the IACUC can ask the investigator questions on any aspects of
the proposal. The unique composition of the IACUC allows it to address veterinary,
safety, public concerns, and research questions. The IACUC ensures compliance
by thorough examination of the proposal prior to approval and subsequent communication
with the investigator after initiation of the work. During the semi-annual inspection
of facilities, the work areas are evaluated, and every year the ASP is renewed
and questions or changes are expressed. Throughout the course of the study,
the IACUC is at liberty to send a representative to visit the animal research
area, and in the case of a possible infraction any employee, is encouraged to
approach the IACUC with concerns. In this fashion, the IACUC oversees the animal
studies performed at the institution.
Received 5/17/94; accepted 7/20/94.
Animal Welfare Act 7 Usc 2131 et. seq. (PL 89-544, August 24,
1966; amended PL 91-579, December 24, 1970; amended PL 94-279, April 22, 1976;
amended PL 99-198, December 23, t985).
The Public Health Services Act as amended by the Health Research Extension
Act, PL 99-158, November 20, 1985 (42 U.S.C. 289d).
Animal Welfare, 9 CFR, Parts 1,2, and 3.
Public Health Service Policy on Humane care and Use of Laboratory Animals,
Guide for the Care and Use ofLaboratory Animals. NIH Publication
No. 85-23. Revised 1985.
US Government Principles for the Utilization and care of Vertebrate Animals
Used in Testing, Research and Training. Federal Register, Vol. 20, No. 97, May
National Institutes of Health. NIH Policy Manual Chapter 3040-2: Animal
Care and Use in the Intramural Program. Appendix 1—Animal Study Proposal.
Article is posted with permission from the authors and Lab Animal Magazine (http://www.labanimal.com).