Protocol Review - Lab Animal 26(3), 1997

Optimal Animal Use

One of an IACUC’s primary responsibilities is to ensure that the number of animals proposed for use are the minimum necessary for the study. The Great Eastern University IACUC members took this responsibility seriously. In conjunction with the animal resources division, they developed a database to enable researchers to procure certain tissues or organs from animals to be euthanized in unrelated studies. The committee wanted a paper trail for any use of animal parts, and therefore instituted a system of “exempt” review, whereby investigators received IACUC permission to obtain these tissues or organs without submitting a full protocol. Investigators using tissues or organs obtained from a slaughterhouse followed the same procedure.

The system worked well, until a new veterinarian arrived at the university. Citing the procedures used at his former institution, he accused the IACUC of violating the Animal Welfare Act (AWA). Specifically, he said, the regulations define an animal as “any live or dead dog, cat, nonhuman primate [etc.] which is being used, or is intended for use for research, teaching, testing, experimentation, or exhibition purposes, or as a pet.” He said that there was no ambiguity at all in that definition, and therefore any sharing of animal tissues or organs requires an IACUC protocol and review, just as if it were a study with live animals.

Needless to say, the IACUC was not pleased. A review of the definitions provided in the AWA regulations did not help to resolve the problem, nor did a review of the AWA’s published explanatory comments. In fact, those documents suggested that the veterinarian was correct. A telephone call to the USDA resulted in an ambiguous response, implying that a gray area may exist. To add to the confusion, some IACUC members believed that the discussion was immaterial because the protocols did not involve the use of whole animals. Others felt that asking investigators to fill out an entire protocol form was the more intelligent option, and the IACUC would have to bite the bullet and review them.

How would you approach the problem facing this IACUC?

Don’t Sweat the Legal Issue

James D. Henderson, Jr., DVM, MS

The IACUC’s policy to permit the use of animal organs or tissues from animals euthanized for other committee-approved projects does not violate the regulations of the AWA. In fact, using tissues obtained from slaughterhouses or animals in unrelated studies is an exemplary way to promote the 3Rs (refinement, reduction, replacement of animals) in biomedical research. In spite of what the policy was at the new DVM’s previous employer, animal tissues and organs do not constitute whole animals (live or dead). The IACUC has no responsibility under section 3.31 of the AWA to review protocols that involve only animal tissues or organs. On the other hand, if an institution purchased the animal and harvested tissues or organs from the animal as part of the primary research protocol, then the new DVM would have a case. While the database that the IACUC developed to track the use of animal parts is laudable, it is not legally necessary, either.

The issue of exempting the use of animal tissues or organs from full protocol review by the IACUC is not as well-defined, as indicated by the USDA’s response to the inquiry from Great Eastern University. It is important, however, to distinguish between needed and required. Clearly, there are times when there is a need for an animal use protocol although only animal tissues are being used in a research project. This might include the use of tissues containing infectious agents, carcinogens, radioisotopes, or toxic substances. The animal use protocol can serve as a focal point for identifying special shipping, handling, or disposal requirements for the tissues and organs.

The IACUC should discuss the issue of exempting the use of animal tissues or organs, since the new DVM seems concerned about the current practice violating the AWA. The IACUC may elect to modify its policy on the use of animal tissues or organs at Great Eastern University, but this decision is not mandated by AWA regulation.

Henderson is Institutional Veterinarian, Medical College of Wisconsin and Chief, Veterinary Medical Unit, Zablocki VA Medical Center, Milwaukee, WI.
 

Great Eastern: The IACUC Tissue War

Howard M. Kaplan, PhD

Great Eastern IACUC may have to reconsider their approach to their animal care and welfare responsibilities. If the current dilemma is any indication, the old procedures are not as effective as they once were. The committee’s traditional approach to the new veterinarian’s concerns caused it to define the issue—“do we have to conduct full protocol reviews of research that uses dead animal parts?”—more narrowly than necessary: as a result, they truncated their options and left themselves no closer to a solution.

First, they sought comparable precedents: does the IACUC at the new veterinarian’s previous institution really treat the sharing of animal tissues or organs as situations requiring full IACUC review of complete protocols? Apparently so. Next, they sought acknowledged authorities to cite: what does the AWA really say about an IACUC’s responsibilities vis-á-vis dead animals, and do USDA representatives view the Act as relevant to tissues, organs, and other parts of dead animals? Finally, they attempted to redefine the issue so it would not seem to apply to the Great Eastern situation: since the USDA’s stance apparently leaves some room for maneuvering, how about if we local IACUC folks stipulate that dead animal parts are outside the Act’s purview and, therefore, not our concern? When none of these approaches provided compelling support for the IACUC’s no-protocol-for-dead-animal-parts position, Great Eastern was ready to respond in the time-honored way: CYA (Cover Your Accountability). They would ask investigators to fill out the complete protocol forms and give full IACUC reviews to those forms.

The Great Eastern IACUC members have only side-stepped the dilemma. A more productive resolution requires a less traditional approach. Rather than treating the problem as a given and seeking ways to get around it, they could begin with the solution they want and seek ways to support or justify it. For example, to support the position that tissues and other parts of dead animals are not equivalent to the dead animals with which the AWA regulations are concerned, the committee could first find out the Act’s developers’ intent when they included dead animals in the definition. The March 15, 1989 Federal Register includes a discussion of how and why the Secretary responded to the “numerous comments” prompted by USDA’s proposal to define an animal as any live or dead dog, cat, or nonhuman primate. The writer explains, “The word dead was added to the definition of animal as part of the 1970 Amendments to the Act, due to the mistreatment of animals obtained for euthanasia and laboratory specimens...We agree that many of the standards published elsewhere in this issue of the Federal Register, would not apply to dead animals1.”

A brief analysis of the above comments indicates that not only did the original AWA not include dead animals, but one could easily view the term’s use here as a misnomer. In fact, the amended definition of dead animals relates to a concern about mistreatment of live animals that are being prepared for death; not to the dead animals themselves, and, therefore, not to tissues, organs, or any other parts of dead animals.

If there is any issue, it lies with the IACUC’s responsibility for overseeing the conditions, preparations, and processes that affect the animal’s euthanasia. The new veterinarian’s previous school notwithstanding, the AWA, as amended, provides no basis for requiring IACUC review of research on any parts of dead animals, or their cadavers for that matter. As a point of contrast, I’d note that the USPHS regulations concerned with the welfare of vertebrate animals, and the protection of human subjects from research risks, is quite clear that both relate only to the living: Any live, vertebrate animal and human subject means (only) a living human individual 2, 3.

The Great Eastern IACUC should announce that, effective immediately, they will not require full protocols from researchers who intend to use only tissues or other parts of dead animals. At the same time, the IACUC should incorporate the AWA/PHS paper trail in easily accessible files. Not only will this document the rationale and support for their decision; it might also prove valuable if and when the new veterinarian decides to test the whistle-blowing waters.

Kaplan is a former IACUC Chair and is currently Administrator of IACUC support service. He is Director of Research Services and Sponsored Programs, Georgia Southern University, Statesboro, GA.

References

1. Federal Register, Department of Agriculture, Animal and Plant Inspection Service, 9 CFR Parts 1, 2, and 3. Animal Welfare; Proposed Rules. pp. 10821-10954. Government Printing Office, Washington DC, March 15, 1989.

2. PHS Policy on the Care and Use of Laboratory Animals, OPRR, 1996.

3. Protection of Human Subjects, OPRR Reports, Revised 6/18/91.

OPRR and USDA/Animal Care Response on Applicability of the Animal Welfare Regulations and the PHS Policy to Dead Animals and Shared Tissues

Nelson L. Garnett, DVM, and W. Ron DeHaven, DVM

The use of dead animals or parts of animals in research is an area for which a clear institutional policy can help prevent serious misunderstandings and possible compliance problems. The new veterinarian is partially correct in that the definition of “animal” in the Animal Welfare Act (AWA) includes the statement “any live or dead.” However, the definition for “research facility” in the AWA and in 9 CFR [part 1.1 and part 2.30 (a) (1)] states that a research facility is an entity that “uses or intends to use live animals.” Likewise, the Public Health Service (PHS) Policy is applicable to activities involving live vertebrate animals.

Ordinarily, neither the Animal Welfare Regulations nor the PHS Policy protocol review requirements apply to dead animals in the research facility setting. Despite this, many institutions choose to require protocol review for all activities involving living or dead animals. This places the decision-making control at the IACUC level, and the practice may best serve the interests of the institutions for a variety of regulatory and nonregulatory reasons (e.g., public relations, liability, occupational safety).

The use of shared tissues and slaughterhouse material is an effective application of the “three Rs,” and is encouraged where scientifically appropriate. It is also important, however, to avoid the temptation to misuse the dead animal exemption to circumvent policy and regulation. OPRR and USDA/Animal Care are in agreement that a proposal involving animals to be killed for the purpose of using their tissues, or one that involves project-specific antemortem manipulation, is not exempt from protocol review. Likewise, the belief of some of IACUC members that the sole determining issue is whether or not whole animals are involved is incorrect. In all cases, a “paper trail” is important to document that an institution has applied the appropriate standards to the acquisition, use, and disposition of animals.

PHS grant applicants using shared animal tissues or slaughterhouse materials are advised to specify the origins of the tissues when describing their proposed use in an application, especially if the “no” box is checked on the vertebrate animal block of the face page. Any reference to the use of animal tissues in the application is likely to trigger questions about IACUC approval. Therefore, an explanation in the application that the tissues will come from dead animals as a by-product of other IACUC-approved studies, or from a slaughterhouse, will help avoid delays in the peer-review process.

Garnett is Director, Division of Animal Welfare, Office for Protection from Research Risks, National Institutes of Health, Rockville, MD. DeHaven is Acting Deputy Administrator, Animal Care, US Department of Agriculture, Riverdale, MD.