The Public Health Service Responds to Commonly Asked Questions

This report was prepared by the staff of the Division of Animal Welfare, Office for Protection from Research Risks, National Institute of Health, in Bethesda, Maryland. [The Animal Welfare Division of OPRR was renamed Office of Laboratory Animal Welfare (OLAW) in 2000.]

The National Institutes of Health's (NIH's) Office for Protection from Research Risks (OPRR) is responsible for developing, implementing, and overseeing compliance with the Public Health Service (PHS) Policy on the Humane Care and Use of Laboratory Animals (Policy). The PHS Policy, along with the U.S Department of Agriculture's (USDA's) Animal Welfare Regulations, are the two principal federal documents setting forth requirements for animal care and use by institutions using animals in research, testing, and education. A primary function of OPRR in assisting institutions in implementing PHS Policy is to respond to policy-related questions.

The following represent a few of the most commonly asked questions from institutions and the OPRR responses:

1. Are avian embryos covered by the PHS Policy, i.e., must their proposed use be reviewed and approved by institutional animal care and use committees (IACUCs)?

PHS Policy is applicable to proposed activities that involve live vertebrate animals. While embryonal stages of avian species develop vertebrae at a stage in their development prior to hatching, OPRR has interpreted "live vertebrate animal" to apply to avians (e.g., chick embryos) only after hatching.

2. May our institution apply the requirements of the PHS Policy exclusively to activities that are supported by the PHS? In other words, may we apply different requirements for application and proposal review when the proposed work is funded by another agency or is it to be conducted with internal institutional funds?

Institutional adherence to PHS Policy is a requirement for all activities supported by the PHS, most commonly through NIH grants or contracts, but also including other forms of PHS support such as collaborations and postdoctoral stipends. Since the 1985/1986 revisions to the PHS Policy, the vast majority of institutions filing Animal Welfare Assurances with OPRR have chosen to apply the Policy requirements to all activities involving animals at their institution.

Until 1989, dual mechanisms with PHS-supported and non PHS-supported activities were theoretically possible. With the finalization in 1989 of Part 2 of the USDA regulations, which includes administrative requirements for proposal review, veterinary care, and personnel qualifications, such dual systems are impractical. Part 2 of the USDA regulations are virtually identical to the PHS Policy. Thus, institutions using species covered by the USDA regulations (which currently exclude mice and rats) must establish programs and follow procedures identical to those required by the PHS Policy in order to meet USDA requirements. A more pragmatic reason for having a uniform institutional policy has to do with the public relations dilemma of trying to defend a double standard of humane care for animals. Accordingly, institutional policies should be designed with an emphasis on the desired outcome of appropriate humane care and use of all animals at the institution.

3. Our institution requires that when the IACUC meets, not only must a majority of the members be present, but that the quorum must include the institutional veterinarian and a nonaffiliated member. Is this requirement in keeping with PHS Policy?

Two issues are actually contained in this question: (1) Must the veterinarian and/or nonaffiliated member be present for all formally convened meetings of the IACUC? and (2) May an institution impose requirements more stringent than the corresponding provision of the PHS Policy? The PHS Policy is silent on the first question. OPRR has interpreted the Policy to provide that, with respect to the IACUC, all members are equal. Thus there is no requirement that the veterinarian and/or the nonaffiliated member be present for every IACUC meeting. Attention should be paid by institutions to attendance at IACUC meetings ensuring that an appropriate mix of members attends all meetings and that frequent absences from such meetings by any member are avoided. No member may be excluded from any IACUC function (e.g., semiannual reviews). A history of nonattendance by IACUC members, especially those required by statute, will always arouse the suspicion of a site visitor or inspector.

With regard to the second question, institutionally imposed requirements that exceed those of the PHS Policy are not proscribed by the Policy. Additional requirements may be imposed by the institution at its discretion, bearing in mind that the spirit of the PHS Policy is to promote humane care and use of animals, while facilitating the pursuit of legitimate scientific objectives.

4. Is it permissible under PHS Policy to reimburse the nonaffiliated member of the IACUC?

Meeting fully the letter and spirit of the PHS Policy (and USDA regulations) requires that the nonaffiliated IACUC member be completely disinterested in the institution's profit or benefit from proposed activities that involve animals. While in the vast majority of instances effective nonaffiliated IACUC members may be willing to serve without reimbursement, in other instances remuneration may allow for participation by effective individuals that would not otherwise be possible. Both OPRR and USDA maintain that nominal compensation is permissible without jeopardizing a member's nonaffiliated status, if it is only in conjunction with service on the IACUC. The level of reimbursement varies from payment of travel and related expenses, such as parking and meals, to modest monetary payments for participation in this capacity. The dollar amount of compensation, if any, should not be so substantial as to be considered an important source of income or to influence voting on the IACUC.

5. In fulfilling its requirements under PHS Policy and USDA regulations, must the IACUC inspect every laboratory or other site where investigators use animals?

When considering IACUC responsibilities for semiannual review, it is important to keep in mind that the institution, usually acting through the IACUC and/or the facility veterinarian, is responsible for all animal-related activities of the institution, regardless of where animals are maintained or the duration of their stay. The PHS Policy allows institutions some discretion regarding specific methods to assure compliance, but the institution is clearly responsible for what happens to animals in investigators' laboratories. The degree, method, and frequency of IACUC oversight depends a great deal on the nature of the activity. For example, satellite holding facilities or areas where surgical manipulation is conducted should always be included in the semiannual review. Other activities, such as routine dosing, weighing, or immunization of animals in laboratories, may be monitored using other methods such as random evaluation.

Inclusion of these laboratories in the semiannual IACUC review would be another way to satisfy the PHS Policy requirements. In any case, the IACUC must have access to all investigators' laboratories for the purpose of verifying that activities involving animals are conducted in accordance with the proposal approved by that committee.

6. The PHS Policy requires semiannual IACUC inspection of all facilities where animals are held for 24 hours or more, while the USDA regulations require such inspections of sites where animals are kept for 12 hours or more. How should our IACUC deal with this discrepancy?

The PHS Policy requires compliance with the Animal Welfare Act. The USDA regulations apply to animal study areas where USDA-covered species are maintained for more than 12 hours. These areas of the facility must be included in the semiannual review. The PHS Policy definition of satellite facility and duration of stay requirements remain unchanged, and may be applied to species such as rats and mice that are covered by the Policy but not by USDA regulations. The important point to remember is that the institution remains accountable for all activities involving animals, regardless of any technical differences in definitions and time limits. Again, institutional policies should be designed with an emphasis on the desired outcome of appropriate humane care and use of all animals at the institution.

7. To what extent, if any, is the IACUC responsible for assessing the scientific merit of proposals it reviews?

Peer review of the scientific merit of a proposal is considered to be the purview of the PHS funding component, acting through an initial review group (IRG). The PHS Policy requires the funding component to verify that the IACUC has reviewed and approved animal activities before the PHS awarding unit makes an award. Additionally, the IRG has the authority to raise specific animal concerns. The primary focus of the IRG is scientific merit, whereas the primary focus of the IACUC is animal welfare. It is evident, however, that there is some overlap of function between the two bodies.

Although not intended to conduct peer review of research proposals, the IACUC is expected to include consideration of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals in Testing, Research, and Training (PHS Policy) in its proposal review process. Principle II calls for an evaluation of the relevance of a procedure to human or animal health, the advancement of knowledge, or the good of society. Other references (sections IV.C. I and IV.D. 1.) include language such as "consistent with sound research design," "rationale for involving animals," and "in the conduct of scientifically valuable research," which presumes that the IACUC will consider in its review the general scientific relevance of the proposal. The presumption is that a study that could not meet these basic tests would be inherently invalid or wasteful and, therefore, not justifiable.

8. The PHS Policy requires that the IACUC "conduct continuing review of activities" at least every 3 years, while the USDA regulations require such review annually. How can our IACUC best meet both these requirements?

The frequency of IACUC consideration of approved, ongoing activities is one of the few areas in which the PHS and USDA have differing requirements, that is, PHS requires it at least once every 3 years, whereas USDA requires it annually. While USDA's exclusion of rats, mice, and birds allows for dual mechanisms of IACUC monitoring of activities involving USDA- covered species annually and activities involving all other species triennially, many institutions will choose to establish uniform procedures that satisfy both of these federal requirements.

It is helpful in considering this issue to refer to the evaluation of ongoing activities by use of the term monitoring, as opposed to the function that the IACUC performed at the outset of a new activity and at the expiration of an approved activity, which may be called review. OPRR has interpreted the PHS Policy to require an institutional process that provides review of proposed activities, with committee approval for a specified period of time not to exceed 3 years. This review and approval may be accomplished by either convened committee action or by a designated reviewer/expedited review process that meets the PHS Policy requirements of Section IV.C.2.

During this period of approval, monitoring may be done on an annual basis to meet USDA requirements. The purpose of monitoring is to ensure that no changes have taken place inadvertently in the approved activity that might require further review by the IACUC and that any new requirements of the PHS, USDA, or the institution are transmitted to the investigator. Monitoring need not require convened IACUC or designated reviewer/expedited action. A relatively simple mechanism to meet both federal requirements is to circulate annually to all investigators with IACUC-approved activities a standard form giving current basic information, such as IACUC approval number, IACUC approval date, title of project, and species used. The investigator then notes that either no changes have taken place, or he/she describes any changes that have occurred. Responses are reviewed by an IACUC-designee for assessment of the changes reported. Any changes to the approved activity that are deemed of sufficient magnitude to merit further consideration may then be presented to the IACUC. All of these dispositions should be documented as official IACUC actions.