1. Introductory remarks Deviations and departures from the Guide 8 th Edition can be a difficult concept to fully comprehend. The following slides discuss selected “should” statements. Several specifically described exceptions, an approved departure example, and guidance on using Appendix 9 of ACORP (version 4) to document an approved departure are presented.

2. The Continuing Saga of Deviations & Departures Joan T. Richerson, DVM Assistant CVMO Presented at 2013 PRIM&R IACUC Conference March 18, 2013

3. Selected “Should” Statements with specifically described Guide 8 th edition exceptions Note: Exceptions are not departures from the Guide; need not be reported to the IO in the semiannual report. “Should” statement Specifically described Guide exception Implications for the IACUC Food and Fluid Regulation: “The objective when these studies are being planned and executed 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 the conduct of some physiological, neuroscience, and behavioral 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 as prescribed in the Guide, and the IACUC approves the restriction, this would be a specifically described Guide 8 th edition exception.

4. Selected “Should” Statements with specifically described Guide 8 th edition exceptions “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 (see also section on Behavioral and Social Management).” (pg. 51) If the IACUC approves an appropriate justification (i.e. scientific basis, incompatibility, or veterinary care issue) for the single housing, then it is an example of a specifically described Guide 8 th edition exception. Note: Exceptions are not departures from the Guide; need not be reported to the IO in the semiannual report.

5. Selected “Should” Statements with specifically described Guide 8 th edition exceptions Note: Exceptions are not departures from the Guide; need not be reported to the IO in the semiannual report. “Should” statementSpecifically described Guide exception Implications for the IACUC Prolonged restraint: “Prolonged restraint, including chairing of nonhuman primates, should be avoided …” (pg. 29) “…unless it is essential for achieving research objectives and is specifically approved by the IACUC (NRC 2003b).” (pg. 29) If the IACUC grants approval because the investigator has scientifically justified the prolonged restraint and met the guidelines for restraint described in the Guide, this would be a specifically described exception based on scientific justification.

6. Selected “Should” Statements with specifically described Guide 8 th edition exceptions Note: Exceptions are not departures from the Guide; need not be reported to the IO in the semiannual report. “Should” statementSpecifically described Guide exception Implications for the IACUC Non-pharmaceutical grade (NPG) chemicals and other substances: “The use of pharmaceutical-grade chemicals and other substances ensures that toxic or unwanted side effects are not introduced…They should therefore be used “... when available, for all animal- related procedures (USDA 1997b …” (pg. 31) The use of non- pharmaceutical-grade chemicals and other substances should be described and justified in the animal use protocol and be approved by the IACUC (Wolff et a,. 2003); for example, the use of non-pharmaceutical grade chemical or substance 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 investigator justifies the use of a NPG agent in their protocol and complies with other Guide considerations related to the use of non-NPG agents in order to meet a scientific goal, and the IACUC approves the use, this would be a specifically described Guide 8 th edition exception.

7. Selected “Should” Statements with specifically described Guide 8 th edition exceptions Note: Exceptions are not departures from the Guide; need not be reported to the IO in the semiannual report. “Should” statementSpecifically described Guide exception Implications for the IACUC Euthanasia method that deviates from AVMA Guidance: “…methods should be consistent with the AVMA Guidelines on Euthanasia (AVMA 2007 or later editions).” (pg. 123) “Unless a deviation is justified for scientific or medical reasons, … (pg. 123) If the IACUC approves an investigator’s scientific or medical justification for a method of euthanasia that deviates from the AVMA Guidelines on Euthanasia but the method is consistent with other guidance for euthanasia outlined in the Guide, this would be a specifically described exception.

8. When does a specifically described exception to a “Should” Statement become an “Approved Departure”?

9. ACORP Appendix 9 (example) ACORP Appendix 9 Departures from “Must” and “Should” standards in the Guide (2011) VERSION 4 Briefly summarize the “Must” or “Should” standard, and provide the number(s) of the page(s) on which it appears in the Guide. ► “Regulation of food or fluid intake may be required for the conduct of some physiological, neuroscience, and behavioral research protocols. Body weights should be recorded at least weekly and more often for animals requiring greater restrictions (NRC 2003b).” (pg. 31)

10. ACORP Appendix 9 (example continued) Describe the specific alternate standard(s) that will be met on this protocol, and how they will be monitored. ► Rhesus monkeys will be weighed every two weeks, as opposed to the Guide recommendation of at least weekly, to minimize the negative effects of anesthesia on appetite and behavioral test performance. Body weight and body composition analysis using EchoMRI™ will be collected every two weeks; in addition, food consumption (number of biscuits consumed – compared to number consumed during ad libitum feeding), urine output (gross observation of waste pan), and overall attitude and activity will be tracked and recorded on a daily basis.

11. ACORP Appendix 9 (example continued) Provide the scientific, veterinary medical, or animal welfare considerations that justify this departure. ► As part of this study, the animals will be food restricted to 90% of their ad libitum consumption of a diet high in Omega-3 fatty acids. In a previous experiment, anesthetizing the animals weekly to measure body weights caused inappetence and weight loss in the monkeys, and interfered with the behavioral testing essential to the study. Measuring body weights while the animals are anesthetized for BCA will minimize the confounding effects of anesthesia, while the health and well-being of the animals will be monitored daily as described above.

12. ACORP Appendix 9 (example continued) ACORP App. 9 Last Name of PI ► XXXXXX Protocol No. Assigned by the IACUC ► YYYY Official Date of Approval ► 03/07/13 ________________________________________________________ The date the IACUC approves the “approved departure” is entered in the header for Appendix 9 as shown above. Note: The completed appendix 9 may be copied (with the PI name and the protocol number redacted) for inclusion in semiannual reports.

13. Confused? Still have questions? CONTACT : Office of Laboratory Animal Welfare Division of Compliance Oversight olawdco@mail.nih.gov olawdco@mail.nih.gov 301-915-9466