The PHS Policy requires institutions to establish and maintain proper measures to ensure the appropriate care and use of all live vertebrate animals involved in research, research training, and biological testing activities that are conducted or supported by the PHS. It is applicable to all PHS-conducted or supported activities involving such animals. The major provisions of the Policy are as follows:

• A written assurance stating that the institution will comply with the Policy must be submitted to, and accepted by, OPRR before the institution undertakes any activity supported by PHS resources that involves animals. Approval of an assurance is for a time period up to 5 years. As part of the assurance, the institution must provide:
• a listing of every branch or component of the institution;
• the lines of authority for administering and enforcing the program;
• the qualifications and responsibilities of the participating veterinarian and the percent of time devoted to those duties;
• the membership list of the IACUC and the procedures that they will follow;
• the health program for personnel working in the facilities;
• a synopsis of the training and instruction on humane care and the minimization of the use of animals that are offered to those involved in the research and animal care program;
• the gross square footage of each animal facility, the species, and the average daily inventory, by species, of animals in each facility;
• and any other pertinent information requested by OPRR.
• The IACUC, as required by the Health Research Extension Act, must review the care and treatment of animals in all study areas and facilities of the research institution every six months. The PHS Policy further defines this requirement as a review of the institution’s program for humane care and use of animals and the facilities (including satellite facilities), every six months, and the preparation of a report of this review to the appropriate institutional official. A satellite facility is a containment outside of a core facility or centrally designated or managed area in which animals are housed for more than 24 hours.
• The IACUC, according to the PHS Policy, must be composed of at least five members. It must review each proposed research project, and significant changes to ongoing projects, to confirm that they will be conducted in accordance with the Animal Welfare Act, are consistent with the Guide for the Care and Use of Laboratory Animals, and meet a variety of additional requirements including the minimization of pain, discomfort, and distress.

• The IACUC, according to the PHS Policy, must conduct a continuing review of ongoing research projects, and must conduct a complete review at least once every three years.
• The IACUC, by law, must provide a report to NIH every 12 months. The PHS Policy specifies that this report is to be submitted through the Institutional Official and will identify any change in the program that would place the program in a different category, any change in the description of the program, any change in the IACUC membership, and the dates that the IACUC conducted its semiannual evaluation. In addition, the IACUC must report any continuing non-compliance, serious program deviation, or program suspension to OPRR as it occurs.
• OPRR staff, according to the PHS Policy, may conduct site visits to institutions in order to assess the adequacy of the program and the institution’s compliance with the Policy. Approximately 10 site visits are made per year.

The USDA requires the registration of all non-Federal research facilities that perform research utilizing animals, rather than the assurance required by PHS. This registration must be updated every three years. Their jurisdiction currently extends to all laboratory warm-blooded animals except birds, laboratory rats and mice. They require the following:

• Institutions must provide their animals with care that meets or exceeds USDA standards for veterinary care and animal husbandry. These standards include requirements for handling, housing, feeding, sanitation, ventilation, shelter from extreme weather, and separation of species when necessary.
• The IACUC, as required by the Animal Welfare Act, must be composed of at least three members. It must review the institution’s program for humane care and use of animals, and the facilities including the study areas every six months, and prepare a report of its review to the appropriate institutional official. A study area, unlike a satellite area specified by OPRR, is defined in the regulations as a containment outside of the core facility or centrally designated or managed area in which animals are housed for more than 12 hours.
• The IACUC, according to USDA regulations, must review all new proposals to assure that the activities are in accordance with the USDA regulations. Assessments that they must make, not explicitly identified in the PHS regulations but incorporated by reference, include requirements stated in the Animal Welfare Act that the investigator has considered alternative procedures when more than momentary pain or distress is likely to occur, and that no animal will be used in more than one major operative procedure unless it meets one of the criteria listed for exception.
• The IACUC, according to USDA regulations, must conduct a continuing review of ongoing research projects at appropriate intervals but no less than annually. This differs from the PHS Policy, which requires this review every three years.
• Each facility, as required by the Animal Welfare Act, must provide a report to USDA on or before December 1 of each year providing assurances with regard to the professional standards governing care, and that the principal investigators considered alternatives to painful procedures. In addition, a variety of information specific to animals is requested, including data on the number of animals participating in research by species, and categorized by levels of pain that they did or did not experience.
• USDA, as required by the Animal Welfare Act, undertakes at least one compliance inspection per year of each research facility. These inspections are unannounced.

AAALAC accredits active animal care and use programs, including animals, facilities, equipment, professional, technical, and administrative support, and policies and programs for institutional responsibilities, animal husbandry and veterinary care. Any public or private institution maintaining, using, importing, or producing animals for the purpose of scientific research, teaching or testing may be accredited. All animals used or to be used in research, teaching, or testing are to be included and evaluated.

• The Guide for the Care and Use of Laboratory Animals serves as the basic guide to the establishment of specific standards for accreditation.
• Site visits are normally conducted every three years. However, interim or additional follow-up visits may be required to confirm the correction of deficiencies or if there are major changes in program or facilities.
• An annual report, which generally provides an update on any changes to the program and the IACUC from the previous year, is required annually.

As can be seen, while there are often similar requirements, the details are often different (different reports, different reporting times, different inspection periods, etc.).

In order to put potential issues and solutions into the appropriate context, members identified the intended level of protections, i.e., the objectives that must be achieved if the program of animal care and use is to be considered effective. It is the members’ view that the protections that should be achieved by a program of animal care and use should be consistent with various principles articulated in the Guide for the Care and Use of Laboratory Animals. As such, they concluded that a credible policy has to achieve the following elements:

• Ensure that the total program of animal housing, environment, and care provides the achievement of good health and well-being of animals and minimizes variations that might affect research results.
• Ensure that the research investigators follow the principles articulated in the Guide, i.e., the design and performance of procedures on the basis of relevance to human or animal health, and advancement of knowledge for the good of society; use of appropriate species, quality and numbers of animals; avoidance or minimization of discomfort, distress, and pain in concert with sound science; use of appropriate sedation, analgesia, or anesthesia; provision of appropriate husbandry by qualified persons; and the conduct of experimentation only by, or under the close supervision of, qualified and experienced persons.
• Ensure that the personnel conducting and supporting the animal care and use program are sufficient in number, and adequately and appropriately trained.
• Ensure active oversight and evaluation of the institution’s animal program, procedures and facilities through the use of IACUCs committed to good science and good animal care and empowered to carry out its objective.

These objectives recognize, at their core, that the goal of animal research is to reduce human disease and suffering, that animals are essential for the conduct of research, and that good animal care and good science go hand-in-hand. In addition, both the institution and the Federal agencies have an obligation to assure the public that animals are being used humanely. In examining existing legislation, regulations, policies and practices, the members firmly agreed that any changes proposed to reduce regulatory burden should be consistent with the achievement of these objectives.

Following the development of the objectives that a credible animal care and use program must achieve, the members identified those issues that were of concern. This list included issues related to the legislation, the regulations and the inconsistency between the agencies on some aspects and interpretation of the regulations, and policies and practices of the agencies. It should be noted that the purpose of the workgroup was not necessarily to come to consensus. While there was general agreement on the issues and the proposed solutions, there was not necessarily unanimity on each.

• Redundancy of program reviews and inspections – Members raised the issue of the redundancy of reviews and inspections of programs by the three organizations having oversight responsibility, and the resultant paperwork. IACUCs currently are required by the Health Research Extension Act and the Animal Welfare Act to conduct both an in-depth review of the institution’s program for the humane care and use of animals, and an inspection of its facilities, every six months. In addition, current law also requires that the USDA inspect every facility once a year. While the intensity of the USDA inspection is not specified in law, the USDA current policy is to inspect "every animal in every facility." Furthermore, AAALAC conducts a full accreditation site visit every three years for those institutions that voluntarily seek accreditation. As a result, each institution is having its programs and facilities reviewed a minimum of 3 times per year, and a minimum of 4 times per year for AAALAC-accredited institutions in the years that it conducts its site visit. The paperwork requirement related to these multiple reviews is significant. This redundancy is particularly burdensome for large institutions where a large number of facilities must be inspected. While in some sense, setting an ideal time period between inspections is arbitrary, a frequent comparison source is the Joint Commission on Accreditation of Healthcare Organizations’ (JCAHO) accreditation review of hospitals that occurs once every three years.
• Inconsistency among yearly reports required by OPRR, USDA, and AAALAC – OPRR requires that the IACUC submit a yearly report detailing changes to the program and IACUC membership that have occurred over the past year, the dates that the semi-annual inspections and the semi-annual reviews were conducted, and the dates that the reports were provided to the Institutional Official. No submission date is specified, the only requirement being that it be provided every 12 months.

  USDA, by statute, requires a report by December 1 of every year that provides assurances with regard to the professional standards governing care, and that the principal investigators considered alternatives to painful procedures. In addition, a variety of information specific to animals is requested, including data on the number of animals participating in research by species, categorized by levels of pain that they did or did not experience.

  AAALAC requires an annual report that provides a program and facility update. As is the case with OPRR, there is no required submission date but it is strongly suggested that it be consistently submitted at the same time, every 12 months.

  Members observed that coordination among the three organizations could likely yield a common report that would reduce duplication and overlap while satisfying the needs of all three organizations.

• Inconsistency between USDA and OPRR on protocol reviews.
• Timing of protocol reviews - OPRR policy requires that the IACUC conduct a continuing review of each previously approved ongoing study at intervals determined by the IACUC, with a complete review at least once every three years. The purpose of the review is to assure that the research project is consistent with the PHS Policy, the Animal Welfare Act, and the Guide unless there is an acceptable reason for departure. The review must also assure that the project is addressing a variety of requirements identified in the policy document regarding the avoidance or minimization of pain, animal care, and personnel training.

The USDA regulations require that continuing review of the activities be conducted to assure consistency with the Animal Welfare Act. Timing is at the discretion of the IACUC but, unlike the OPRR guidance, the review must occur not less than annually.

• Performing protocol reviews for other institutions participating in a multi-site project – There was some confusion regarding the requirements imposed on institutions or their investigators that are taking the lead in a multi-site project. Specifically, there was a concern that the lead investigator or institution was responsible in some way for the adherence of the participating institutions to the approved protocol. It was clarified in discussions with OPRR that it is the responsibility of the lead institution and the PHS awarding unit to ascertain that all participating institutions have a negotiated assurance with OPRR. If not, the awarding unit is to notify OPRR to negotiate such an assurance. With assurances in place, each institution would be responsible for adhering to the PHS policies.
• Several USDA requirements would benefit from reexamination - The members identified several USDA requirements that might benefit from a reexamination as they are not perceived to be effective in their current form. Those identified are as follows:
• Documentation of literature searches of alternative research procedures - The Animal Welfare Act (Section 13 (a)(3)(B)) requires that the principal investigator consider alternatives to any procedure likely to produce pain and distress. USDA regulations (9 CFR, Part 2, Section 2.31 (d)(1)(ii)) go on to require a written narrative description of the methods and sources used to determine that alternatives are not available when pain and distress may be caused. Animal Care Policy #12 defines how to be in compliance by stating that, at a minimum, the written narrative should include the databases searched or other sources consulted, the date of the search, the years covered by the search, and the keywords and/or search strategy used to identify alternatives to the procedure. The scientific community contends that this rarely will provide an understanding of the thought given by the scientist to the examination of alternatives and the best methodological approach to the hypothesis being tested. In addition, while committed to the principle of using the least painful procedures, the members thought the IACUC should be determining documentation requirements since it has, at its core, a mandate to address the "3R’s" of reduction, replacement, and refinement.
• Limitations on major operative procedures - The Animal Welfare Act (Section 13(a)(3)(D,E) states that no animal can be used in more that one major operative experiment except in the case of scientific necessity or special circumstances defined by the Secretary, and exceptions may be made only when specified by the research protocol. The regulations (9 CFR, Part 2, Section 2.31(d)(1)(x)) essentially restate the law but allow routine veterinary procedures, procedures required to protect the well-being of the animal, or other special circumstances as defined by the Administrator on an individual basis, as exceptions. Animal Care Policy #14 goes on to clarify that multiple surgeries are permissible if part of the same protocol and approved by the IACUC, but not permissible if it involves separate protocols. Exceptions to this policy must be approved by the Deputy Administrator, Animal Care, APHIS.

Members support the dual objectives of minimizing the pain and distress that individual animals must experience and minimizing the number of animals used in research. However, members noted that the restriction to a single survival surgery for the life of an animal does not necessarily support the reasonable use of animals, nor does it reduce the number of animals used in research. In fact, this restriction may cause more animals to be used in research. This restriction is particularly burdensome for research with nonhuman primates, which may live for 20-50 years, depending on the species. Many humans undergo multiple surgeries during their lifetime and, if performed after full recovery from the previous surgery, there is no evidence that subsequent surgeries are more traumatic to the individual. In addition, members observed that the definition of major surgery (currently defined in USDA regulations and the Guide as any surgical intervention that penetrates and exposes a body cavity, or produces permanent impairment of physical or physiological functions), is not current as it does not consider the advances made with minimally invasive surgical techniques, i.e., laparoscopy. Finally, the restrictions are so inflexible that they will not be able to adapt to new technologies or the future need for long-term measurement of physiological variables, e.g., the possible need to replace instrumentation in animals involved in aging studies. The net result is that the policy may not strike the appropriate balance between the objectives to minimize pain and limit the number of animals used in research to the minimum, with possibly more animals used for research and exposed to surgery than necessary.

• Pain classifications and the associated paperwork requirements - The USDA currently classifies pain experienced by animals in research in the following three categories: C-experiment produces no pain, distress, or use of pain-relieving drugs; D-experiment produces pain or distress which is appropriately relieved; and E-experiment causes pain or distress but relief of that pain or distress would adversely affect the results of the experiment. Members expressed the concern that USDA may be changing the existing pain classifications to create a larger number of categories through a policy change. In addition, they are concerned that those experiments in category D are subject to documentation requirements verifying the consideration of alternative procedures. The apparent basis for this requirement is USDA’s interpretation of Section 2.31(d)(ii) of the regulations that the PI consider, and document the consideration of, alternatives to procedures that may cause more than momentary pain or distress to animals. Members contend that animals whose pain is being relieved should be exempt from documentation requirements.
• Animal housing, environmental, and management standards – Members observed that such standards should be based on current scientific standards rather than relatively arbitrary engineering standards. For example, the USDA regulations (9 CFR Part 3, Section 3.80b(2)(iv)) state that the minimum space requirement for animals that are housed together is the USDA minimum space requirement for a single animal multiplied by the number of animals housed. However, members contend that such a policy is shortsighted and ultimately is a disadvantage to animals that would benefit from being housed in groups, but who are not, because institutions don’t have cages that meet these rigid requirements. They cite a study by the National Research Council entitled the Psychological Well-Being of Non-human Primates, which concludes that the requirement contained in the regulations is "indefensible" because cage design should be the result of a thoughtful understanding of the needs of animals, not by determining multiples of body weight calculations. It goes on to say that "…many nonhuman primates in single cages today would benefit from a compatible cagemate, even if the cage sizes do not precisely meet the letter of the law." This policy of emphasizing the advantage of group housing even if it results in slightly less space per animal is also advocated in the Guide for the Care and Use of Laboratory Animals.

Although the USDA regulations do allow the IACUC to make exceptions to these space requirements for group housing, the process entails needless paperwork. It is burdensome, at the least, to be required to request an exception to a regulation that is scientifically flawed.

• Inconsistent interpretation of regulations and policies and unfamiliarity with the research environment – Given the involvement of multiple oversight organizations, the members reported frequent instances of receiving conflicting interpretations of similar requirements across organizations and within the same organization itself. Members believed this to be an issue that creates sufficient confusion within the research community that it needs to be addressed by all three organizations - OPRR, USDA, and AAALAC. Protocol review was cited as an example. USDA requires an annual review of research projects while OPRR requires a three year review. Confusion exists as to (1) the difference in review cycles, and (2) what is expected at the OPRR three year review. There is a similar discrepancy in requirements for facility inspections. Coordination of efforts and/or staff training about specific differences in requirements for USDA, OPRR, and AAALAC personnel would eliminate some of this confusion. In addition, members also reported that USDA inspectors, because of USDA’s broader mandate (meat inspections, animal park inspections, etc.), are sometimes unfamiliar with research and the research environment.
• Complexity of regulations governing the transportation of animals and biological materials from non-human primates – Regulations administered by the Department of Interior’s Fish and Wildlife Service (FWS) to protect endangered species, and their rigid interpretation of these regulations, have the unintended consequence of impeding research, and can also be life-threatening. These regulations flow from the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Under the regulations, procedures were established to regulate the import and export of imperiled species covered by the treaty. There are three levels of control depending on the degree to which the animal is imperiled. The highest level of control is on those animals threatened with extinction, where a permit is required from both the importing and exporting country; those not threatened with extinction, but likely to be so without trade regulation, require an export certificate; and species for which any of the 100 signatory nations has designated a restriction requires an export permit, a re-export certificate, or a certificate of origin.

  For those animals that are threatened with extinction, the regulations apply, not only to the transport of the animals themselves, but also to its "parts and products". The FWS has interpreted this phrase to include materials routinely used by research scientists such as blood, tissue, DNA, etc. While this phrase is not explicitly mentioned in the second category listed above, the FWS has extended it to that category also. The end result is that for routine international collaborations, in which samples are drawn from animals bred specifically for research, the research institution must navigate this process which incurs a minimum time delay of a month, and likely significantly longer on average. However, even worse than this delay is the potential for personal harm. A workgroup member described an incident involving an individual bitten by a zoo animal (non-endangered) in Canada where a blood sample from the animal could not be immediately shipped to the U.S. for tests to ascertain the possibility of transmission of a deadly disease.