Survey of Regulatory Documents

1. Survey of Regulatory Documents “Another flaw in the human character is that everybody wants to build and nobody wants to do maintenance.” Kurt Vonnegut (1922 - ), Hocus Pocus

2. Law vs. Regulations vs. Guidance

3. USDA is King… • Most important agency regulating animal research is the United States Department of Agriculture (USDA). • Congress gave the USDA broad authority to regulate animal research in the Animal Welfare Act. • USDA established Animal Welfare Act Regulations (AWAR), which take precedence over regulatory documents produced by all other agencies. • The USDA has published a Policy Manualthat clarifies how some of the language in the USDA Animal Welfare Act Regulations should be interpreted.

4. Animal Care • The Animal Care office in the Animal and Plant Health Inspection Service at USDA administers the AWAR

5. Animal Welfare Act USDA Animal Welfare Act Regulations Part 2 Regulations Part 1 Def of Terms Part 3 Standards Definitions § 1.1 Subpart ALicensing- §2.1-2.11 Subpart B Registration- §2.25-2.27 Subpart C Research Facilities- §2.30-2.38 Subpart D Veterinary Care (exhibitors)- §2.40 Subpart E ID of Animals- §2.50-2.55 Subpart F Stolen Animals- §2.60 Subpart G Records- §2.75-2.80 Subpart H Compl with Stds/Holding Periods- §2.100-2.102 Subpart I Miscellaneous §2.125-2.133 Subpart A Dogs and Cats - §3.1-3.19 Subpart B Guinea Pigs and Hamsters- §3.25-3.41 Subpart C Rabbits- §3.50-3.66 Subpart D Nonhuman Primates- §3.75-3.92 Subpart E Marine Mammals- §3.100-3.118 Subpart F Other Warm-Blooded Animals- §3.125-3.142 Guidance: Policy Manual Policies 1-29

6. Lab Mice and Rats are Not Regulated by USDA "Animal means any live or dead dog, cat, nonhuman primate, guinea pig, hamster, rabbit, or any other warm blooded animal, which is being used, or is intended for use for research, teaching, testing, experimentation, or exhibition purposes, or as a pet. This term excludes: Birds, rats of the genus Rattus and mice of the genus Mus bred for use in research, and horses not used for research purposes and other farm animals, such as, but not limited to livestock or poultry used or intended for use for improving animal nutrition, breeding, management, or production efficiency, or for improving the quality of food or fiber. With respect to a dog, the term means all dogs, including those used for hunting, security, or breeding purposes." (USDA AWAR Part 1, Definitions)

7. Public Health Service (PHS) Policy • PHS Policy on Humane Care and Use of Laboratory Animals (“PHS Policy”) incorporates compliance with the USDA AWAR. • Congress gave PHS authority to regulate animal research at its awardees in the Health Research Extension Act of 1985. • PHS Policyis functionally equivalent to USDA regulations. • OLAW provides written guidancethat clarifies PHS Policy, equivalent to USDA Policy Manual. • PHS insiders refer to PHS Policy as “the” PHS Policy.

8. Office of Laboratory Animal Welfare • The Office of Laboratory Animal Welfare at NIH administers PHS Policy

9. Health Research Extension Act of 1985 PHS Policy on Humane Care and Use of Lab Animals U.S. Govt Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Main Body Report of the AVMA Panel on Euthanasia Guide for the Care and Use of Laboratory Animals I. Introduction II. Applicability III. Definitions IV. Implementation by Institutions A. Animal Welfare Assurance B. Functions of the Institutional Animal Care and Use Committee C. Review of PHS-Conducted or Supported Research Projects D. Information Required in Apps and Proposals Submitted to PHS E. Recordkeeping Requirements F. Reporting Requirements V. Implementation by PHS A. Responsibilities of the Office of Laboratory Animal Welfare B. Responsibilities of PHS Awarding Units C. Conduct of Special Reviews/Site Visits D. Waiver Guidance: OLAW Letters and Articles

10. PHS Policy Definition of Animal • "Animal- Any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes." (PHS Policy, Section III.A) • Covers lab rodents, but only live ones.

11. US Government Principles- IRAC, 1980’s • Part of PHS Policy. Critical concepts for IACUC reviewers. I. The transportation, care, and use of animals should be in accordance with the Animal Welfare Act (7 U.S.C. 2131 et. seq.) and other applicable Federal laws, guidelines, and policies. II. Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society. Justification for Use of Animals

12. III. The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered. IV. Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals. Alternatives- the 3 R’s Philosophy of IACUC Pain/Distress Evaluation

13. V. Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents. VI. Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure. Sole Use of Paralytics Prohibited Need for Endpoint Criteria

14. VII. The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated. VIII. Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals. Veterinary Care Required Training Required

15. IX. Where exceptions are required in relation to the provisions of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle II {justification for animal use},by an appropriate review group such as an institutional animal care and use committee. Such exceptions should not be made solely for the purposes of teaching or demonstration. IACUC Review and Oversight Needed

16. VA Programs Follow USDA AWAR and PHS Policy • Federal law requires VA animal research programs to comply with USDA Animal Welfare Act Regulations (Animal Welfare Act, item 2(e)), reiterated in 1200.7, item 4b(5)) • VHA Handbook 1200.7 (Use of Animals in Research) stipulates that VA programs follow PHS policy whether or not PHS funds are utilized(1200.7, item 4b(4))

17. VA Policy- 1200.7, “Use of Animals in Research” • Equivalent to USDA regulations but without criminal penalties. • Similar to PHS Policy- to get PHS funds, PHS Policy must be followed; to get VA funds, VA Policy must be followed. • Philosophy of VA Policy: USDA and PHS provide adequate framework for animal research; additional VA policies only needed to address gapsor consistent problems in VA programs.

18. VA Authorizing Legislation; Title 38 United States Code (U.S.C.) Section 7303 VHA Handbook 1200.7, Use of Animals in Research Appendix A: CVMO Contact Info Appendix B: Special Aged Rodent Procurement Appendix C: Occupational Health and Safety Appendix D: Animal Component of Research Protocol (ACORP) Appendix E: VA IACUC Semi-Annual Self-Review Items Sections 1. Purpose 2. Background 3. Definitions 4. Scope 5. Chief Veterinary Medical Officer (CVMO) VA Central Office 6. Organization at VA Medical Centers 7. VMU Operations at the VA Medical Center 8. Institutional Animal Care and Use Committees 9. Visits to VA Animal Facilities by Non-VA Federal Regulators 10. Occupational Health and Safety 11. References Main Body

19. Association for Assessment and Accreditation of Laboratory Animal Care, International (AAALAC) Rules of Accreditation • Participation in AAALAC program is voluntary for most of the world, but mandatory for VA programs. (1200.7, item 7e) • ORD pays for a contract that covers all VA programs. (1200.7, item 7e) • All accredited programs must agree to follow AAALAC’s rules.

20. Office of Res Oversight (ORO) and Office of Res and Development (ORD)- Missions Secretary of the VA Undersecretary for Health ORO Network/VISNs ORD Monitoring Research Compliance Performing and Supporting Research Developing Policy, Funding Research

21. ORO and ORDAnimal Research Policies Secretary of the VA Undersecretary for Health ORO Network/VISNs ORD Memo- “What to Report to ORO” (VISN Research Policies) 1200.7, Use of Animals in Research

22. Memo- What to Report to ORO, September 8, 2005 • Page 2, item 4: Stipulates format of deficiency reports • Pages 3-4: 12 types of animal research deficiencies that must be reported to ORO Note: Handbook 1200.7, paragraph 8g and subparagraphs, has additional guidance on what must be reported, how it should be reported, and who should be notified.

23. Memo- What to Report to ORO, September 8, 2005 Note: VHA Handbook 1058.1 (November 19, 2004) entitled "Reporting Adverse Events In Research to The Office of Research Oversight" addresses only reporting requirements for human subjects research programs.

24. ORO/OLAW Documents • ORO has an agreement with OLAW (PHS Policy) to share information. • Item IV.B: “The cooperating agencies agree to share information, to the extent permitted by law, of mutual concern and interest regarding animal welfare at VA and VA-affiliated PHS assured institutions, including, but not limited to, evidence of serious noncompliance with standards for the care and use of laboratory animals, significant adverse findings regarding animal care and use investigated, inspected, or site-visited, and actions taken by the agencies in response to the findings.”

25. Shared Compliance Information • VA ORO has an agreement with OLAW • USDA and OLAW have an agreement with FDA “Conceal a flaw, and the world will imagine the worst.” Marcus Valerius Martialis (Latin poet; 40 AD-103 AD)

26. Managing Regulatory Complexity is Difficult: Some Strategies • Design forms (ACORP , semi-annual review forms) and SOPs to help investigators, IACUC [Tab U], and animal care staff meet regulatory expectations. • Provide training so that forms and SOPs can be used effectively. • Use software to manage tasks of tracking protocol expiration dates, tracking animal use, generating correspondence, agendas and minutes, and generating standard regulatory reports.