Frequently Asked Questions about the Public Health Service - Policy on Humane Care and Use of Laboratory Animals

STEPHEN POTKAY, VMD, NELSON GARNETT, DVM, JOHN G. MILLER, DVM,
CYNTHIA L. POND, DVM, MS, AND DENIS J. DOYLE, MA

Division of Animal Welfare, Office for Protection from Research Risks, National Institutes of Health, 6100 Executive Boulevard, Suite 3B01, MSC 7507, Rockville, MD 20892-7507. [The Animal Welfare Division of OPRR was renamed Office of Laboratory Animal Welfare (OLAW) in 2000.]

Abstract: Adherence to the provisions of the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals and related U.S. Department of Agriculture Animal Welfare regulations is a prerequisite for receiving PHS support for conducting animal-related activities. As one of its duties specified in the PHS Policy, the Office for Protection from Research Risks (OPRR) here provides guidance regarding questions that have been raised by institutions seeking to comply with those requirements. These questions include institutional reporting requirements, collaborative activities, performance of multiple survival surgeries, care and use of cold-blooded vertebrates, tracking of animal use, animal study areas, and other Animal Care and Use Committee issues. In reviewing these questions and answers, readers are asked to keep in mind that many of these issues are highly context-specific and that over-generalization is to be avoided.

The Office for Protection from Research Risks (OPRR) of the National Institutes of Health (NIH) develops, implements, and oversees compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (1). The PHS Policy and the U.S. Department of Agriculture (USDA) Animal Welfare Regulations (2) are the two principal federal documents setting forth requirements for animal care and use by institutions that use animals in research, testing, and education. One of the primary functions of OPRR is to assist institutions in implementing PHS Policy by responding to policy-related questions (3-5). The following are several questions frequently asked by institutions and the OPRR responses.

1. Could you provide examples of "significant" and "minor" deficiencies and suggest appropriate methods for reporting them in the Institutional Semiannual and Annual Reports?

The term "significant deficiency," used in the PHS Policy and the USDA Animal Welfare Regulations, refers to any facility or program deficiency that is or may be a threat to the health or safety of animals. Program or facility deficiencies, including accidents and natural disasters, which cause injury, death, or severe distress to animals, are, by definition, "significant." Although it is not possible to provide an exhaustive listing of examples, some illustrations of significant facility deficiencies include failures in heating, ventilating, and air conditioning systems and their associated electrical systems; inoperative watering systems; and general power failures of sufficient duration to affect critical areas such as isolators, barriers, surgical suites, and intensive care units. Minor deficiencies in animal facilities include infrequent findings of peeling or chipped paint, burnt-out light bulbs, missing floor drain covers, and similar problems for which immediate solutions generally are not necessary to protect life or prevent distress. Repeated detection of minor, area-specific problems, however, should suggest to management that there are substantial program deficiencies resulting failure to develop effective policies or plans or to take corrective actions to prevent recurrences.

Significant program deficiencies generally originate in an institution's failure to fully understand or implement some aspect of its animal care and use program, as required by the PHS Policy (6). Most commonly, they are related to failure of the Institutional Animal Care and Use Committee (IACUC) to function according to commitments made in its institutional assurance. Specific difficulties often are connected with the animal research proposal review process, veterinary care, or institutional training programs, inadequacies of which may pose real or potential threats to the health or safety of animals.

Institutional semiannual reports should categorize any deficiencies found during the IACUC's semiannual program and facility review as being major or minor. For both categories, a reasonable and specific plan must be described for the correction of each deficiency and a schedule for accomplishing the correction. When deficiencies involve serious or continuing noncompliance with the PHS Policy, serious deviations from the Guide for the Care and Use of Laboratory Animals (henceforth referred to as the Guide)(7), or the IACUC suspension of any activity, the circumstances and actions taken must be reported promptly to OPRR as required in section IV.F.3.a-c. of the PHS Policy. Reporting of such deficiencies should not be deferred for inclusion in the institutional annual report. It also should be noted that the USDA Animal Welfare Act regulations require that significant deficiencies not corrected within the time frame of the initial corrective plan and schedule be reported within 15 business days to the Animal and Plant Health Inspection Service (APHIS) and to any Federal agency funding that activity.

2. Investigators at our institution often collaborate with scientists in other countries and sometimes go abroad to collect samples from captive wild animals maintained in zoological collections and in research colonies. Is it necessary for our IACUC to review and approve their protocols? What about samples that are obtained by citizens of the foreign country and sent to our institution?

All animal activities supported by the PHS must be reviewed by the IACUC of the domestic-assured awardee institution that receives such support. Foreign institutions that serve as performance sites must also have Assurances on file with OPRR. The OPRR considers institutions whose scientists are engaged in such collaborative work accountable for the animal-related activities from which they receive animals or animal parts. When a foreign institution holds a PHS Assurance, it also is expected that the institution will conduct the study in accordance with the applicable host-nation's policies and regulations. In the specific case of sample collection, the review should take into account the species involved, nature of the specimen, and the degree of invasiveness of the procedure, giving appropriate consideration to the use of anesthetics and analgesics. In cases in which samples are obtained directly by citizens of a foreign country for subsequent shipment, recipient PHS-supported investigators should determine the proposed methods of collection and present that information to their IACUC for review. Prior to sample collection and regardless of whether specimens are obtained by an awardee institution's investigator directly or by persons in a foreign country, the OPRR strongly recommends that each awardee institution consult with other agencies of the U.S. government concerning importation requirements. Depending on the species involved and the nature of the specimen, the following may be of assistance: the U.S. Fish and Wildlife Service, Department of the Interior (for compliance with the International Convention on Trade in Endangered Species of Fauna and Flora [CITES]), APHIS, U.S. Department of Agriculture (regarding potential animal pathogens), and the Centers for Disease Control and Prevention (concerning importation of nonhuman primates and potential pathogens of human beings).

3. The PHS Policy requires that the IACUC consist of at least 5 members, whereas the Health Research Extension Act states that the committee be composed of at least 3 members. Regulations of the Animal Welfare Act are consistent with the latter. In constituting our committee, which requirement should we adhere to? Also, would you explain the difference between Institutional Official and Chief Executive Officer (CEO)?

When your institution is a recipient of PHS support for animal-related activities, its IACUC must consist of at least 5 members who are appointed by the institution's CEO. It is required that these individuals be qualified through experience and expertise to provide oversight for the institution's animal programs, facilities, and procedures. At a minimum, IACUCs must include a veterinarian, a practicing scientist experienced in animal research, a person whose primary concerns are in nonscientific areas, and a person who is unaffiliated with the institution except as a member of the IACUC. It should be noted that the unaffiliated individual may not be a member of the immediate family of a person who is affiliated with the institution. The veterinarian, in addition to possessing training or experience in laboratory animal science and medicine, must have direct or delegated program responsibility for animal-related activities at the institution. Although an individual who qualifies to fill more than one of the aforementioned categories may be appointed to do so, it is still required that the committee consist of 5 members. For purposes of the PHS Policy, the institutional official is that person in the organization having the administrative and operational authority to commit institutional resources to ensure that the animal care and use program will comply with requirements of the PHS Policy. In some institutions, the institutional official and the CEO may be one and the same, whereas in other institutions, particularly large ones, the CEO may be further removed from the day-to-day program oversight.

4. To describe the responsibilities and qualifications of veterinarians who will participate in our animal program, will the provision of a curriculum vitae suffice? May the veterinarian be unaffiliated with the institution?

It has been OPRR's experience that curricula vitae of veterinarians provided with the submissions of new or renewal Assurances of Compliance usually do not contain the specific information required by the PHS Policy. Therefore, this office recommends that Section III.B. of the Assurance be used to provide the names, professional degrees, and the number of years of pertinent training in laboratory animal medicine for each veterinarian participating in the animal care and use program. An indication of the individuals' training and experience in managing the species involved also is helpful. This should be followed by a description of the duties and responsibilities of those persons and a statement regarding the direct or delegated authority of the individuals to implement the PHS Policy and the provisions of the Guide. It also is important to indicate the approximate percentage of time that those individuals will contribute to the program. In cases in which there is not a full-time veterinarian on the staff, the anticipated number and frequency of visits by the veterinarian should be indicated. Failure to provide the required information will necessitate follow-up requests by OPRR and can result in lengthy processing delays.

In all cases, the veterinarian responsible for implementing the program is, by definition, affiliated with the institution, whether as an official employee or through a written contract for service. It may be noted that some institutions find it helpful to retain the services of a Diplomate of the American College of Laboratory Animal Medicine who is available to consult with its institutional veterinarian for the resolution of certain problems (8).

5. Our IACUC has received a proposal in which nonhuman primates from our institution's breeding colonies would be subjected to multiple cesarean sections in order to obtain viable offspring and to maximize cost effectiveness and the reproductive utility of the colony of a threatened species. Because cesarean sections commonly are performed in other species such as companion animals, will our IACUC have to consider the proposal in the context of a multiple survival surgery?

While discouraging the performance of multiple survival procedures on specific animals, the Guide states that the IACUC may consider special circumstances involving requests to do so. An example of a potentially justifiable request given in the Guide involves performing multiple procedures on an animal when the procedures are related components of a research project. The USDA Animal Welfare Regulations, which are applicable under the PHS Policy, provide further guidance on this matter. Under the regulations, multiple major operative procedures are permitted when 1) scientifically justified by the investigator (in writing) and approved by the IACUC or 2) when needed as a routine veterinary procedure or to protect the health and well-being of an animal, as determined by the attending veterinarian. Proposals that involve exposing an animal to multiple major surgery under conditions not covered by items 1 or 2 must receive prior authorization by the Administrator, APHIS, USDA. When considering proposals such as the one described, specific requests should be made to APHIS on a cases-by-case basis. In its evaluation of such requests, the IACUC must understand that it was the intent of Congress to prohibit subjecting animals to multiple major (survival) surgeries in unrelated research protocols, and that species that are threatened or endangered were not distinguished from those that are not on a threatened or endangered list. Neither the PHS Policy nor the USDA Regulations consider cost savings alone as an adequate justification for performing multiple major surgeries on an animal.

6. Use of amphibians, reptiles, and fishes in research appears to be increasing at our institution. However, neither the PHS Policy nor the Guide provide specific guidelines for our IACUC to follow in its consideration of research proposals involving the care and use of these animals. What advice can OPRR offer to assist our IACUC?

The PHS Policy is intentionally broad in scope and does not prescribe specifics about the care and use of any species, assigning that task to the IACUC and allowing for professional judgment. Many of the principles embodied in the Guide, although not specifically addressing cold-blooded vertebrates, generally can be adapted to animal care and use programs for various kinds of amphibians, reptiles, and fishes. Substantive guidance pertinent to specific species and situations is available in publications prepared by organizations having interest in the appropriate care and use of these species in laboratory and field studies (9-18). It is clear, however, that individual requirements for these 3 classes of vertebrates, which contain more than 28,000 species that have a diversity of requirements, cannot be addressed in a single set of guidelines. Consequently, the OPRR recommends that the advice of experts be obtained to design and develop studies and suitable housing and care procedures when species not commonly used in research are being considered. The OPRR also suggests that the results of their efforts to devise methods for the care and use of these species be published to serve as an aid to others.

7. Is it necessary for our IACUC to track the numbers of animals used in the various protocols it has approved to ensure that the numbers do not exceed those that were approved in the proposal review process? If so, could you provide guidance on the best means for accomplishing this?

[Outdated]

Although neither the PHS Policy nor the USDA regulations explicitly require an institutional mechanism to track animal usage by investigators under IACUC-approved activities, both require that proposals to the IACUC specify and include a rationale for the approximate number of animals proposed to be used. These provisions implicitly require that institutions establish mechanisms to monitor and document the number of animals acquired and used in approved activities. The OPRR is aware of many institutions at which such mechanisms preclude an investigator from using a single animal in excess of the number approved by the IACUC. Other institutions have reported mechanisms that allow the number of rodents acquired to exceed the number approved by a small percentage (e.g., 5%), although they still may require investigators to obtain and use only the precise number of nonrodent mammalian species approved by the IACUC.

Administrative linkage of animal acquisitions to IACUC approval numbers is the method of choice used by many institutions to track the numbers of animals being acquired under approved activities. Many also have described relatively simple automated data processing systems that will alert the systems' operator and generate a report when an investigator has reached a preset percentage (e.g., 80-90% of the animals approved for that activity). This report then is submitted to the investigator with a request to provide a specific justification if they anticipate that the number of animals ultimately required will exceed the number approved. Small institutions that use limited numbers of animals may choose to maintain a hard-copy log of each IACUC-approved activity, merely subtracting the number of animals acquired for each order from the number approved, with verbal or written notification to the investigator as the number of animals approved is approached. Whatever mechanism an institution chooses, however, it must satisfy the PHS Policy requirement that the number of animals used be limited to the appropriate number necessary to obtain valid results.

8. In conducting its semiannual facility reviews, is it necessary for our IACUC to consider laboratories or other sites where animal procedures or holding activities are conducted only sporadically or for periods of less than 24 h? How does our IACUC determine whether to follow the requirements of the PHS or the USDA regarding the definition of "study area?"

Each assured institution, acting through its IACUC or facility veterinarian, is responsible for all animal-related activities at the institution regardless of where the animals are maintained or the duration of their stay. The degree, frequency, and method of IACUC oversight often depends on the nature of the activity. For example, satellite holding facilities and areas in which surgical manipulations are performed must always be included in semiannual reviews, whereas laboratories in which only routine immunization, dosing, and weighing take place may be monitored by other means such as random site visits and evaluations. Regardless of whether such laboratories are included in the semiannual review process or are monitored by other means, the IACUC must have reasonable access to them for the purpose of verifying that activities involving animals are being conducted in accordance with the proposal approved by the IACUC. The PHS Policy requires compliance with the USDA regulations regarding areas where USDA-covered species are maintained for any purpose for more than 12 h. The term "satellite facility", as defined in the PHS Policy, remains unchanged and is applicable to the housing or holding facilities provided for all vertebrate animals. It is important to keep in mind that the institution is accountable for all activities involving animals, regardless of technical differences in definitions and time limits, and that institutional policies should be designed to obtain the desired outcome of both the PHS Policy and the Animal Welfare Act (namely, the appropriate, humane care of all animals at each institution).

1. Public Health Service. 1996. Public Health Service Policy on Humane Care and Use of Laboratory Animals. U.S. Department of Health and Human Services, Washington, D.C. [Reprint of 1986 edition].

    

2. Animal Welfare Regulations. 1985. Code of federal regulations, title 9 (animals and animal subproducts), subchapter A (animal welfare), parts 1-3 (9 CFR 1-3). U.S. Department of Agriculture, Washington, D.C.

    

3. Division of Animal Welfare, Office for Protection from Research Risks. 1991. The public health service responds to commonly asked questions. ILAR News 33:68-70.

    

4. Division of Animal Welfare, Office for Protection from Research Risks. 1993. Frequently asked questions about the public health service policy on care and use of Laboratory Animals. ILAR News 35:47-49.

    

5. Potkay, S., N. L. Garnett, J. G. Miller, et al. 1995. Frequently asked questions about the public health service policy on humane care and use of laboratory animals. Lab. Anim. 24:24-26.

    

6. McLaughlin, R M. 1993. Institutional animal care and use committee review of animal care and use programs. Contemp. Top. Lab. Anim. 32:12-15.

    

7. National Research Council. 1986. Guide for the care and use of laboratory animals. NIH Publication No. 86-23. Public Health Service, Washington, D.C.

    

8. American College of Laboratory Animal Medicine. 1996. Report of the American College of Laboratory Animal Medicine on adequate veterinary care in research, testing, and teaching. American College of Laboratory Animal Medicine, Cary, NC.

    

9. Ferguson HW. 1984. Fish, p. 1-10. In: Guide to the care and use of experimental animals, vol 2., Canadian Council on Animal Care, Ottawa, Ontario, Canada.

    

10. Institute for Laboratory Animal Resources. 1974. Amphibians. In: Guidelines for the breeding, care and management of laboratory animals. National Academy of Sciences, Washington, D.C.

     

11. Institute for Laboratory Animal Resources. 1991. Recommendations for the care of amphibians and reptiles in academic institutions. National Academy of Sciences, Washington, D.C.

     

12. Scientists Center for Animal Welfare. 1992. The care and use of amphibians, reptiles, and fish in research. Schaeffer, D. O., K. M. Kleinow, L. Krulisch (eds.). Scientists Center for Animal Welfare, Greenbelt, MD.

     

13. American Society of Ichthyologists and Herpetologists, American Fisheries Society, American Institute of Fisheries Research Biologists. 1987. Guidelines for the use of fishes in field research. Fish. J. 13(2):1-14.

     

14. American Society of Ichthyologists and Herpetologists, The Herpetologists' League, and Society for the Study of Amphibians and Reptiles. 1987. Guidelines for the use of live amphibians and reptiles in field research. J. Herpetology (Suppl) 4:1-14.

     

15. Orlans, F. B. 1988. Field research guidelines: impact on animal care and use committees. Scientists Center for Animal Welfare, Greenbelt, MD.

     

16. DeTolla, L. J., S. Srinivas, B. R. Whitaker, et al. 1995. Guidelines for the care and use of fish in research. ILAR J. 37:159-173.

     

17. DeNardo, D. 1995. Amphibians as laboratory animals. ILAR J. 37:173-181.

     

18. Greene, H. W. 1995. Nonavian reptiles as laboratory animals. ILAR J. 37:182-186.