Compliance at the Institutional and Programmatic Level - 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.

Program Compliance

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 in research.

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 are present.

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.

References

Laws
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).

Regulations
Animal Welfare, 9 CFR, Parts 1,2, and 3.

Policies
Public Health Service Policy on Humane care and Use of Laboratory Animals, September 1986.

Guide for the Care and Use of Laboratory 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 20, 1985.

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