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Comment submitted electronically to www.regulations.gov, docket APHIS-2007-0110
On the APHIS Animal Care Policy Manual
The American Physiological Society appreciates this opportunity to comment on the USDA APHIS Animal Care Policy (ACP) Manual. The APS is a scholarly association founded in 1887 to advance understanding of how living systems function. Today there are more than 10,000 APS members throughout the U.S. APS members are involved in research and education in colleges, universities, medical schools, industry, and government. Because physiologists seek to understand how cells, tissues, and organs function in health and disease, their work often involves studying animals as model organisms. The APS has a long-standing interest in animal welfare and is proud of the continuing leadership role it plays in fostering high standards of animal care.
General Comments
It has long been a source of concern to the research community that the ACP Manual, which is a guidance document, has been used as if it had the authority of a regulatory document. It is our hope that through these comments, the use of the ACP Manual will be placed in a more appropriate context in relation to the Animal Welfare Act and its implementing Regulations.
To facilitate compliance by research institutions with USDA’s requirements and expectations, the APS encourages the Department to conduct a congruency review of the Animal Welfare Act, Animal Welfare Regulations, Animal Care Policies, and the Research Facility Inspection Guide.
The APS endorses the comments provided by the National Association for Biomedical Research (NABR), beginning with its recommendation that the ACP Manual should include language indicating that this is an agency guidance document that does not bind the USDA or regulated entities. There should also be a clear statement that regulated entities are entitled to use alternative approaches to satisfy the requirements of the applicable statutes and regulations.
APS further endorses NABR’s recommendation that each individual Policy include the following language: “USDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance describes the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited.” In addition, each page of the ACP Manual should contain the header, “CONTAINS NON-BINDING RECOMMENDATIONS.”
Finally, APS supports the NABR recommendation that each Policy be reviewed in accordance with Section II, h of the OMB’s Final Bulletin for Agency Good Guidance. This section calls upon agencies to eliminate any use of
“mandatory language such as ‘shall,’ ‘must,’ ‘required’ or ‘requirement’ unless these words describe a statutory or regulatory requirement, or the language is addressed to agency staff and will not foreclose agency consideration of positions advanced by affected private parties.”
The revised language should clarify in each case that alternative means to comply with the guidance provided in the Policies are permissible.
The APS also has the following specific comments on Policies 3, 11, 12, 14, 15, and 17.
Policy #3: Veterinary Care
Pharmaceutical-Grade Compounds in Research
This section of Policy # 3 should be modified to clarify when there is an expectation that pharmaceutical grade drugs and compounds are to be used as opposed to instances when no special justification for non-pharmaceutical grade drugs is required. Situations where pharmaceutical grade drugs would be expected to be used include routine veterinary care for non-research-related health problems and research procedures where the health and well-being of the animal are at risk, i.e., for anesthesia, analgesia, and euthanasia.
Policy #3 currently includes this statement regarding the use of non-pharmaceutical grade compounds in a research context:
“Non-pharmaceutical grade chemical compounds should only be used in regulated animals after specific review and approval by the IACUC for reasons such as scientific necessity or non-availability of an acceptable veterinary or human pharmaceutical-grade product.”
Nevertheless, this policy has created considerable confusion. Many IACUCs interpret Policy #3 to mean that the use of non-pharmaceutical grade compounds in anything other than extraordinary circumstances is prohibited. The Policy should be revised to clarify to IACUCs that use of non pharmaceutical drugs in research protocols should be permitted as long as appropriate precautions are taken and the drugs are administered with proper veterinary oversight. The exception to this usage would be cases where the health and well-being of the animals may be risk.
Pre- and Post-procedural Care
The first paragraph of this section of Policy #3 includes this statement:
“However, the attending veterinarian retains the authority to change post-operative care as necessary to ensure the comfort of the animal.”
This section should be revised to state that IACUC approval is not required when the attending veterinarian makes adjustments in post-operative care as necessary to ensure the health and well-being of the animals.
Policy #3 also includes the statement that when research protocols include the potential for pain and distress, “specific details must be approved by the attending veterinarian or his/her designee” (emphasis added.) However, this differs from the wording of the Animal Welfare Regulations, which states that such procedures must “involve, in their planning, consultation with the attending veterinarian or his or her designee” (emphasis added). Beyond the fact that there is no regulatory basis to require the attending veterinarian’s (AV) approval of specific protocol-driven procedural details, requiring AV approval of procedural details would, by default, grant the AV sole power to veto any experimental protocol involving the potential for pain and distress. In addition, the requirement that details be listed in the animal activity proposal is inconsistent with the Animal Welfare Regulations, which do not require such a proposal.
Jump to Top Policy 3 Policy 11 Policy 12 Policy 14 Policy 15 Policy 17Policy #11: Painful Procedures
As NABR has noted, the definition of a painful procedure in Policy #11 differs from the definition contained in Part 1 of Subchapter A, Animal Welfare Regulations. The AWA definition includes the following modifying clause “...that is pain in excess of that caused by injections or other minor procedures.” The definition in Policy #11 should be revised to conform to the definition in the regulations. It is essential that the entire definition be used when an IACUC must determine whether a procedure is likely to cause more pain than that incurred by an injection or other minor procedure because that is critical to the decision as to whether an appropriate anesthetic or analgesic agent should be administered.
Policy #11 has been wrongly interpreted by some VMOs, IACUCs, and others as requiring investigators to conduct an alternatives search even in cases where the procedures do not meet the definition of a painful procedure contained in the Regulations. An example of this would be non-survival, acute surgical procedures. Using the definition contained in the Regulations, there would be no reasonable expectation for the animals to experience pain beyond that of an injection. Therefore, the investigator should not be required to conduct an alternatives search. The same could be said for the use of Freund’s Adjuvant when performed by trained and qualified personnel using appropriate anesthetics and/or analgesics.
Pain
USDA is encouraged to reconsider its “examples of procedures that can be expected to cause more than momentary or slight pain.” Freund’s Complete Adjuvant (FCA) may cause results that can range anywhere from “momentary or slight” to “severe” pain. However, as written this section has been misinterpreted by IACUCs and VMOs to mean that FCA is always painful and always requires classification as pain category D or E when in some cases it could be a Category C procedure. Policy #11 should be clarified to state that with appropriate pain relief, FCA does not cause severe pain and does not automatically require classification in pain category D or E.
Distress
The Institute for Laboratory Animal Research is expected shortly to publish an update to its 1992 report on distress in laboratory animals. The USDA should review this study before implementing any substantive revisions to the elements of its policy on distress.
The APS wishes to point out that the examples of procedures that may cause more than momentary or slight distress are confusing. Paralysis or immobility in a conscious animal when there is no painful procedure does not always result in more than momentary or slight distress. However, the Policy is being misinterpreted to mean that this must always be classified in pain Category E. Policy #11 should be clarified to state that paralysis or immobility in the absence of a painful procedure does not necessarily cause severe distress and does not automatically require classification in category E.
Jump to Top Policy 3 Policy 11 Policy 12 Policy 14 Policy 15 Policy 17Policy #12: Consideration of Alternatives to Painful/Distressful Procedures
Policy #12 is considered by far to be the most onerous and least beneficial to animals of all 29 APHIS Animal Care Policies. Policy #12 exceeds both the Animal Welfare Act and the Animal Welfare Regulations and now constitutes a de facto major rule promulgated without appropriate Federal Register notice and opportunity for public comment as required under the Administrative Procedures Act.
There has been considerable discussion over the years concerning Policy #12’s reliance upon literature searches as the optimum way to identify alternatives to potentially painful or distressful procedures. Although Policy #12 was recently modified to include personal discussions at conferences and colloquia or with subject expert consultants, the modified Policy has onerous requirements in terms of how such discussions must be documented. As currently written, this Policy does not encourage the application of the best and most humane science to answer a research question. Rather, it has become a bureaucratic exercise. Emblematic of this shift is the fact that Policy #12 provides no opportunity for scientists to expound upon the efforts they have undertaken to replace, reduce and refine potentially painful or distressful procedures.
Policy #12 has been further expanded in the field by some VMOs through the inappropriate application of highly prescriptive interpretations of how many databases need to be searched and what constitutes an adequate literature search strategies. In some cases institutions have been cited under Policy #12 because the VMO disagreed with the IACUC’s determination that an adequate alternative search had been performed. This usurps a role delegated to the IACUC.
Policy #12 has also created problems due to inconsistent interpretation and enforcement by VMOs. Individual VMOs have adhered to different standards in terms of whether an alternatives search is adequate, whether the requirement is to search one or more databases, whether search strategies were appropriate, and how scientists and IACUCs determined the relationship of the search to the proposed research and/or teaching activity. The latter is an issue of special concern because Policy #12 does not acknowledge the necessity of repetition in teaching activities.
This Policy describes alternatives or alternative methods in terms of the 3 Rs—reduction, refinement, and replacement—but does not take into account instances where such alternatives have been incorporated in the design of the study itself. For example, this Policy does not allow an investigator to elaborate on a proposal which incorporates a refinement wherein the use of the latest means of managing potential pain and distress as recommended by the veterinarian. This would constitute not only the consideration of but the actual use of alternative methodologies. The same holds true if a proposal includes a power analysis that determines the least number of animals needed to produce statistically valid findings. In that case, not only has an alternative been considered, it has in fact been used. When this occurs, additional justification through a literature search should not be required.
Although engineering standards are generally considered undesirable with respect to animal welfare requirements, for alternatives searches, it might be helpful if the USDA were to formulate a template for optimal responses. This template should be written in clear, unequivocal language, which would reduce the likelihood of disagreement about whether sufficient information was provided and/or the search was adequate.
Another option would be to eliminate the current Policy and replace it with the actual sections of the AWA and the Regulations regarding consideration of alternatives.
Jump to Top Policy 3 Policy 11 Policy 12 Policy 14 Policy 15 Policy 17Policy #14: Major Survival Surgery: Single vs. Multiple Procedures
As noted by NABR, Policy #14 appears to prohibit the use of animals in more than one proposal with a major operative procedure. This limitation exceeds the authority provided in the AWA and the Regulations. Both the Act and the Regulations require that usage for more than one major operative procedure be scientifically justified. However, neither places a blanket prohibition on involving animal in more than one study with a major procedure. Policy #14 should be revised to make it consistent with AWA statutory and regulatory language.
Policy #14 should also be revised to clarify what constitutes a major operative procedure. Some IACUCs define any procedure that involves the opening of a body cavity as a major procedure, even when the procedure is conducted laparoscopically. However, laparascopic procedures cause minimal discomfort and pose a minimal health risk. Similarly, some IACUCs consider a tiny laminectomy to collect a sample of spinal fluid to be a major operative procedure. If animals that have undergone such minimal procedures are considered ineligible for use in a separate study with a major survival surgery, the result is an increased number of animals needed to accomplish research objectives. Neither of these outcomes are in keeping with the intent of the Act, the Regulations, or the 3Rs.
The APS also recommends revising the last sentence of the first paragraph of Policy #14 to allow animals that have had major operative procedures as part of proper veterinary care ordered by the attending veterinarian apart from any research protocol to be included in protocols requiring a major survival operative procedure. A specific exception should be noted for spays and neuters.
Jump to Top Policy 3 Policy 11 Policy 12 Policy 14 Policy 15 Policy 17Policy #15: IACUC Membership
This Policy exceeds the committee membership criteria found in the Animal Welfare Regulations. The Regulations state:
(ii) At least one shall not be affiliated in any way with the facility other than as a member of the Committee, and shall not be a member of the immediate family of a person who is affiliated with the facility. The Secretary intends that such person will provide representation for general community interests in the proper care and treatment of animals.
Laboratory animal users are no less capable of representing general community interest than non-animal users yet may offer expertise not available elsewhere. Laboratory animal users should not be categorically barred from serving as unaffiliated community representatives on IACUCs outside their own institutions.
Jump to Top Policy 3 Policy 11 Policy 12 Policy 14 Policy 15 Policy 17Policy #17: Annual Report
This Policy references AWA Section 2143(a)(7)(A) which requires an annual report from research facilities to include “information on procedures likely to produce pain or distress in any animal.” (Emphasis added.) There is no mention, nor even an implication, of a requirement to report numbers of animals used. Moreover, it is clear that Congress intended for registrants to report animals identified during a prospective assessment of the proposed activities. However, this Policy indicates not only that the information reported be gathered retrospectively but that such animal usage information be based on “an accounting method sufficient to support” the numbers reported. The requirement that the report contain numbers of animals used and be "certified as correct" reinforces the message that this must be a retrospective accounting.
This Policy should include a confirmation that institutions can provide information gathered prospectively as suggested in the Animal Welfare Act.
Jump to Top Policy 3 Policy 11 Policy 12 Policy 14 Policy 15 Policy 17Back to Comments Archive