1. NWI Way VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM VA Animal Research IACUC

2. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM IACUC (Institutional Animal Care and Use Committee) Charged with ensuring compliance ACORP (Animal Component of Research Protocol) Official VA animal protocol form AAALAC (Assoc. for Assessment & Accreditation of Lab Animal Care) Accrediting body for animal research recognized by VA OLAW (Office of Laboratory Animal Welfare) PHS office that administers policy on animal use and care. ORO (Office of Research Oversight) VA advising office on compliance and assurance

3. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM The Components of our Animal Research Program The lines of authority and responsibility for administering the animal research program and ensuring compliance. Marci Mylan, Ph.D., DIRECTOR Omaha Veterans Affairs Medical Center Research and Development Committee Subcommittee of Animal Studies IACUC John Hudson II, Ph.D. Administrative Officer Ellis G. Jensen, D.V.M. P.D. Westenburg, D.V.M. Veterinary Consultants Debra Romberger, M.D. Associate Chief of Staff/Research Service ACOS/R&D Robert Wiegert ARF Supervisor T. Norman Thomas Animal Caretaker Subcommittee of Animal Studies IACUC Ellis G. Jensen, D.V.M. Veterinary Consultant Robert Wiegert ARF Supervisor IACUC Coordinator: Wendy Inselman, 995-3940 Wendy.Inselman@va.gov

4. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM IACUC Self-regulatory body for animal research Responsibilities:  Perform review and oversight functions PHS Policy- The Guide VHA Handbook 1200.7  Perform semi-annual program and facility reviews AAALAC Review this fall NEW ACORP VERSION 4

5. 4 Announcements concerning AAALAC review: 1.Please check expiration dates on all substances (food, drugs, chemicals and other materials). Bob W. will be inspecting for this before Sept. 1 2.Please make sure that all secondary containers are properly labeled.

6. 5 Version 4 is major update over Version 3 – begin use as soon as possible- New forms must be used for review at the September IACUC meeting (August 25 th deadline). Separate files for forms and instructions (instruction files include more detailed explanations, references, and examples) Substantive updates to address new regulatory emphases Harm-benefit analysis Use of non-pharmaceutical agents Managing deviations/departures NEW ACORP VERSION 4 From Central Office:

7. 6 Application to perform animal research http://www.nebraska.va.gov/services/Research/iacuc/iacuc_forms.asp http://www.research.va.gov/programs/animal_research/http://www.research.va.gov/programs/animal_research/.

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9. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM Animal specific forms: OLD 8

10. 9 Version Number NEW FORMS (August 2013) 4 Animal Component of Research Protocol (ACORP) Main Body (ACORP Instructions)Main BodyACORP Instructions Appendix 1Appendix 1– Additional Local Information (ACORP App. 1 Instructions)ACORP App. 1 Instructions Appendix 2Appendix 2– Antibody Production (ACORP App. 2 Instructions)ACORP App. 2 Instructions Appendix 3Appendix 3– Biosafety (ACORP App. 3 Instructions)ACORP App. 3 Instructions Appendix 4Appendix 4-- Ante-mortem Specimen Collection (ACORP App. 4 Instructions)ACORP App. 4 Instructions Appendix 5Appendix 5– Surgery (ACORP App. 5 Instructions)ACORP App. 5 Instructions Appendix 6Appendix 6– Special Husbandry and Procedures (ACORP App. 6 Instructions)ACORP App. 6 Instructions Appendix 7Appendix 7– Use of Patient Care Equipment or Areas for Animal Studies (ACORP App. 7 Instructions)ACORP App. 7 Instructions Appendix 8Appendix 8– Use of Explosive Agent(s) within the VMU or in Animals (ACORP App. 8 Instructions)ACORP App. 8 Instructions Appendix 9Appendix 9– Departures from "Must" and "Should" Standards in the Guide (ACORP App. 9 Instructions)ACORP App. 9 Instructions

11. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM Use of NEW forms: Required submissions: Initial – entire ACORP Annual Continuing review Triennial – entire ACORP Optional submissions: Amendment –entire ACORP with highlighted changes AND all appropriate appendixes Amendment to add new personnel:  expedited- DMR

12. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM Initial / Triennial / Amendments– NEW ACORP 11

13. 12 Substantive updates to address new regulatory emphases Harm-benefit analysis Use of non-pharmaceutical agents Managing deviations/departures Harm-Benefit Analysis is now explicitly addressed in Item B of Main Body

14. 13 Harm-Benefit Analysis ACORP Main Body B.Description of Relevance and Harm/Benefit Analysis. … describe how this research project is intended to improve the health of people and/or other animals, or otherwise to serve the good of society, and explain how these benefits outweigh the pain or distress that may be caused in the animals … ► ACORP Instructions B.Description of Relevance and Harm/Benefit Analysis. (US Government Principles, Principle II) … The IACUC is obligated to weigh the benefits to be gained from the work against potential concerns about animal welfare (AAALAC FAQs, C.3, Guide, p. 27), so it is important for the protocol to provide the information that the IACUC needs to assess this.

15. 14 Substantive updates to address new regulatory emphases Harm-benefit analysis Use of non-pharmaceutical agents Managing deviations/departures Non-pharmaceutical-grade agents are now addressed explicitly in Appendix 3

16. 15 Non-Pharmaceutical Agents Note: Every material that appears anywhere in the ACORP should be listed in item 1, regardless of whether there are any biosafety concerns

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18. 17 Expanded instructions for the table in Item 2 of Appendix 3 are given in the Instructions file 2.Summary of How Materials will be Administered. Provide the details … OLAW requires that only pharmaceutical grade compounds be administered to animals unless the use of non-pharmaceutical grade compounds is justified by scientific necessity and the lack of availability of an acceptable veterinary or human pharmaceutical grade compound (OLAW FAQs, F.4). … Mark with a * each material, diluent, or vehicle to be administered to the animals on this protocol that is not pharmaceutical grade. For each of these, provide the justification for using a non-pharmaceutical grade compound, and describe how it will be ensured that the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, formulation, and pharmacokinetics of the material will be suitable for use in the animals (Guide, p. 31).

19. 18 Substantive updates to address new regulatory emphases Harm-benefit analysis Use of non-pharmaceutical agents Managing deviations/departures Appendix 9 is a new feature in Version 4 of the ACORP and is used to record D EPARTURES FROM “M UST ” AND “S HOULD ” S TANDARDS IN THE G UIDE (2011). ** The Instructions for Appendix 9 include test questions and a flow chart for determining deviations /departures.

20. 19 Appendix 9 is a new feature in Version 4 of the ACORP and is used to record D EPARTURES FROM “M UST ” AND “S HOULD ” S TANDARDS IN THE G UIDE (2011). ***Appendix 9 is used to document DEPARTURES that have been approved by the IACUC for your protocol ***DEPARTURES are determined from “deviations” from the “Guide”— most commonly appear in the following questions: Main ACORP: C.2.c : description of animal use M: husbandry T: endpoint criteria U: termination or removal from protocol V: special procedure Appendices: 2,4,5,6,7

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22. 21 When a deviations is a DEPARTURE and requires Appendix 9 submission

23. When a deviation does not require Appendix 9 submission Example 1 “Should” statement Specifically described Guide exception Implications for the IACUC Food and Fluid Regulation: “The objective should be to use the least restriction necessary to achieve the scientific objective while maintaining animal well–being.” (pg. 30-31) “Regulation of food or fluid intake may be required for some research protocols. Body weights should be recorded at least weekly and more often for animals requiring greater restrictions (NRC 2003b).” (pg. 30-31) If the IACUC confirms that food restriction is scientifically justified and the animals are weighed weekly, and the IACUC approves the restriction, this would be a specifically described Guide 8 th edition exception. No appendix 9 required

24. Example 2 “Should” statementSpecifically described Guide exception Implications for the IACUC Individual housing: “Social animals should be housed in stable pairs or groups of compatible individuals…” (pg. 51) “…unless they must be housed alone for experimental reasons or because of social incompatibility If the IACUC approves an appropriate justification then it is an example of a specifically described Guide 8 th edition exception. No Appendix 9 required When a deviation does not require Appendix 9 submission

25. Example 3 “Should” statementSpecifically described Guide exception Implications for the IACUC Non-pharmaceutical grade (NPG) chemicals and other substances: “The use of NPG substances ensures that toxic or unwanted side effects are not introduced…They should therefore be used “... The use of NPG substances should be described and justified in the animal use protocol and be approved by the IACUC (Wolff et a,. 2003); NPGs may be necessary to meet the scientific goals of a project or when a veterinary or human pharmaceutical-grade product is unavailable.” (pg. 31) If the PI justifies the use of a NPG agent in their protocol and the IACUC approves the use, this would be a specifically described Guide 8 th edition exception. No appendix 9 required When a deviation does not require Appendix 9 submission

26. 25 When a deviation is a DEPARTURE and requires Appendix 9 submission

27. VA NEBRASKA-WESTERN IOWA HEALTH CARE SYSTEM Summary 26 1.READ instructions 2.Answer all questions: Fill in all tables that apply Answer when prompted ► Enter N/A for any item that does not apply 3. Start using new forms for protocols to be reviewed in Sept (August 25 th deadline) 4. Use resources: GUIDE etc. 5. Ask questions