Protection of Animal Subjects in Research

1. Protection of Animal Subjects in Research Nona Phillips, Director, Office of Animal Welfare October 14, 2011 Gerberding 142 University of Washington

2. Which Animals Require Approval? • Laws and regulations apply to “live vertebrate animals” • Eggs: upon emergence from the egg, the animal is covered by laws and regulations • Birds: Upon hatching • Fish & Amphibians: Larval forms (upon emergence from the egg even if the yolk sac is attached) • Rodent Breeding Colonies: all pups born must be included on the protocol; even culls that were not included in experiments

3. Wildlife Studies When is IACUC approval required for a field study? • anytime an animal will be captured, handled, etc. or if the animal’s environment will be disturbed in some substantive way that is expected to affect the animal (such as removing eggs from nests) • anytime animals will be held/housed in the field, such as in a field aviary • simple observation of animals in the field, with no manipulation - IACUC approval is not required

4. Behavioral Studies • All behavioral studies of animals held in UW research facilities require IACUC approval, even if all procedures are non-invasive. • For behavioral studies utilizing aversive stimuli, scientific justification must be provided. The IACUC cannot approve the proposal otherwise (legally or ethically).

5. Are there “Exempt” Categories? • The word “exempt” is not used in the laws and regulations pertinent to use of animals in research and teaching. • Any use of live vertebrate animals, as defined in the laws or regulations, requires exactly the same review and approval process. For example: • If you use left-over blood taken from an animal for clinical reasons, you are not using a live animal for research and so no IACUC approval is required. • If ANY extra blood is taken during the clinical sampling in order to provide it to you for research, then a live animal has been used for research and ALL requirements for review and approval apply.

6. Tissue Sharing • What is “tissue use” vs. “live animal use”? • Tissues obtained from a slaughterhouse do not require IACUC approval because the animal was not euthanized for purposes of the research. • Tissues from another IACUC approved project that are not needed for that project do not require approval, provided: • the animal was euthanized for the approved protocol (not for you) and there were no other changes to the use of the animal in order to provide the tissues to you

7. Is “Sponsored Funding” Required? • A grant or a contract is not a requirement for IACUC protocol approval. However, scientific merit review is required. For scientific merit review the IACUC relies on either: • granting agency review (e.g., NIH, NSF) • internal review by department chair or their designee - some departments have a committee, some appoint a reviewer, etc.

8. Office of Animal Welfare Responsibilities What do we do? • process and help review IACUC (Institutional Animal Care and Use Committee) protocol submissions • review grants and provide IACUC approval information for sponsors • provide courses including species-specific procedure labs • provide personal one-on-one post-approval assistance to researchers via our “Post-Approval Monitoring” (PAM) program • coordinate IACUC semi-annual site visits to animal housing and use locations

9. OAW Structure Administrative Team: processes IACUC submissions and informs PIs of upcoming protocol and training expirations Scientific Reviewer Team: reviews IACUC submissions and grants involving live animals Training Unit: in conjunction with Department of Comparative Medicine veterinary staff, provides courses including species-specific labs, surgery, etc. Site Visit Team: coordinates all aspects of IACUC semi-annual site visits and tracks deficiencies and corrections. Post-Approval Monitor Team: meets with PIs to review protocols and plans, and advise/assist them as needed – a specific OAW staff member is assigned to each PI

10. Other Key Departments:Comparative Medicine (DCM) • Department of Comparative Medicine • houses and maintains species other than non-human primates (NHPs) • provides veterinary care for species other than NHPs • orders animals other than NHPs • Web site (http://depts.washington.edu/compmed/) provides information including: • animal order forms and information • per diem rates • Veterinary Services information

11. Other Key Departments:Washington National Primate Research Center (WaNPRC) • WaNPRC provides many services including: • housing and maintenance of non-human primates (NHPs) • veterinary care for NHPs • animal ordering and project assignment • research support staff • Web site (http://www.wanprc.org/) provides additionalinformation

12. IACUC Protocol Business Process • PI submits new IACUC protocol, annual or 3-year renewal, or changes to an approved protocol • IACUC members receive items twice monthly • IACUC members have 1 week to review and submit questions/comments (members may request Full Committee Review of any item) • IACUC questions/comments forwarded to PI • PI responds back to committee with answers & protocol revisions

13. IACUC Protocol Business Processcont. • an OAW scientific reviewer reviews PI answers/protocol revision • reviewer works with PI on any outstanding issues and then either: • protocol is approved or • protocol is assigned to the agenda for the next monthly convened IACUC meeting if Full Committee Review was/is requested by any IACUC member

14. IACUC Protocol Forms • Forms and other information are on the OAW web site: https://depts.washington.edu/iacuc/ • forms are currently Word documents • active process is ongoing to identify a web solution for protocol development, submission to IACUC and for animal ordering • Note: The web site is being revised to provide much more information. The changes will be on the web very soon.

15. Timing for Submissions to IACUC • Allow plenty of time for IACUC review/approval. Submit items to the OAW as follows: • new or 3-year renewals – at least 2 months prior to when you need to start animal work (longer if the plan is very long and/or very complicated) • annual renewal – 1 month prior to expiration • changes – up to 2 months before you need to implement the changes, depending on complexity of requested changes • adding new personnel – a few days or longer, depending on when training requirements and enrollment in Occupation Health Program are completed

16. Occupational Health (OH) Program • Regulations require that animal health and human health are both protected. • An OH Program for people working with animals, or in animal areas, is required. • You will be provided with OH recommendations for your protocol during the review process, based on species to be used and other factors. • Each individual working with the animals must complete an “Animal Use Medical Screening” form (see OAW web site). Form goes to OH nurse not to OAW – health information is confidential. The nurse will interact directly with the individual.

17. Protocol Assistance • OAW: • can help with determining animal numbers needed • can assist with suggestions for complicated situations such as writing a protocol for providing core services to other researchers • will assist with room changes to your approved protocol by completing a form for the protocol for you! • Veterinarians: • consult with veterinarians in DCM or WaNPRC regarding anesthetics, analgesics, monitoring for potential pain, etc.

18. IACUC Policies • Policies reviewed and approved by the IACUC can be viewed and/or downloaded at: https://depts.washington.edu/iacuc/policies/index.html

19. Grants & Contracts • Competing proposals • Just-in-Time (after submission to sponsor but prior to award - OAW needs to review when potentially fundable score is received) • bring OAW a copy of proposal, note the eGC1 number for the proposal, and in SAGE add “Animal Subjects” as a watcher to the eGC1 • Non-competing proposals • at time of submission bring copy of proposal to OAW • eGC1 automatically routes to OAW for approval • IACUC approval info must be included for animal work at other institutions, if applicable

20. Grant/Contract ReviewBusiness Process • OAW reviews grant and associated UW protocol(s) to assure concordance and if applicable, assures that approvals from other institutions are documented • OAW provides letter to sponsor regarding IACUC approval based on sponsor requirements • OAW can provide other documents as required by the sponsor – let us know what they’ve requested

21. Vertebrate Animals & Sponsor Issues • Most sponsors have requirements associated with proposals for live vertebrate animal work, such as: • IACUC approval for ALL animal work proposed in the application (for all years, not just year 1). • inclusion of all performance sites for the grant, including for companies you may contract with for production of custom antibodies, creation of genetically modified mice, etc. All sites must have an Animal Welfare Assurance. Contact OAW for help.

22. NIH Terms & ConditionsChanges in Scope • Changes in scope require prior approval by NIH and include: • adding use of animals when the grant indicated “no” for animals. The answer is “yes” even if all work will be conducted at a non-UW site (including contracting for custom antibodies). • a change in the animal model (e.g., grant includes mice and you want to add fish or dogs) • addition of a foreign performance site (including for contract antibody production)

23. NIH Terms & ConditionsUse of Funds • NIH funds may only be used for approved activities, so keep in mind: • NIH requires reimbursement if funds are spent on unapproved activities, including salary funds for those who performed them. • Unapproved activities include procedures not in the IACUC protocol as well as procedures performed during a complete lapse of approval (i.e., after 3-year expiration date). • NIH may refuse to make an award if pilot data in a proposal were unapproved.

24. Additional Sponsor Requirements • Many sponsors require that the institution has an Animal Welfare Assurance on file with the NIH Office of Laboratory Animal Welfare (OLAW). • Many expect/require accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care, Int. (AAALAC). • Some (e.g., DOD) require copies of specific documents such as the actual letters from OLAW and AAALAC regarding our Assurance approval and accreditation. Contact OAW for copies.

25. Training • Federal regulations require institutions to: • ensure that animal caretakers are trained and qualified • ensure that researchers are qualified through training or experience to perform the procedures they will conduct • provide training/instruction in minimizing the number of animals to be used and in methods to minimize distress

26. Training Opportunities • Courses are offered on-line and in person • Courses include: • general laws and regulations, • decentralized animal care and record keeping requirements • species-specific labs and certifications as required • facility orientations • Training specific to non-human primates is offered by the Washington National Primate Research Center. • See the Animal Use Training web site for details and course registration instructions: http://depts.washington.edu/auts/index.html

27. Post-Approval Monitoring • Federal regulations require that institutions have methods for helping assure post-approval compliance. • Many functions of the IACUC, OAW and veterinarians help in this regard including facility site visits, monitoring of animals by veterinary staff, etc. • Many institutions have developed formal post-approval monitoring programs with dedicated staff.

28. UW Post-Approval Monitoring Program • Each research group is assigned a compliance advisor from the OAW. • The compliance advisor is a resource for the research group. • The compliance advisor meets once or twice yearly with the PI (and lab manager and/or others per PI’s preference). • Visits include review of protocols, operating procedures, and planned changes, and advice regarding IACUC review requirements.

29. Post-Approval Compliance • Non-compliance can occur even though we are all working together to stay in compliance. • There are several areas of compliance concern related to IACUC approvals including: • post-procedure animal care issues • IACUC protocol related issues, such as: • implementing “Significant Changes” prior to approval • continuing work beyond 3-year expiration (note: regulations disallow administrative extensions of approval)

30. Veterinary Care Issues Examples - Areas where non-compliance may occur include: • post-procedure monitoring of animals to ensure well-being (by responsible party, i.e., veterinary staff and/or research staff) • following of veterinary medical orders by animal care and use personnel or researchers

31. IACUC Protocol Related Issues Examples - Areas where non-compliance may occur include: • conduct of animal-related activities without IACUC approval • failure to adhere to specifics of a protocol (e.g., criteria for euthanasia, anesthetic agent) • continuation of activities after protocol completely expires

32. What if a Non-Compliance Occurs? • The UW’s Animal Welfare Assurance requires a prompt report to OLAW. • The non-compliance must be reported to the IACUC. • The IACUC takes action (such as a letter of counsel to the PI) based on the specifics of the non-compliance. • If federally sponsored work was involved, the sponsor needs to be notified of any disallowed expenditure of funds (e.g., NIH). • AAALAC requires that they are informed also.

33. IACUC Site Visits – Self Regulation • Federal regulations require semi-annual visits to all animal housing and use locations. • The IACUC must assure that: • housing requirements are met for primary and secondary enclosures, including sanitation issues, temperature and air flow issues, animal welfare and enrichment requirements, etc. • procedure related requirements are met, such as dedicated space for surgery • in-date items are used on animals, drug storage is compliant, etc.

34. IACUC Site Visit Business Process • The IACUC conducts semi-annual site visits to animal housing and use rooms during January-April and July-October. • OAW requests available times, in advance, from research groups and then schedules a visit accordingly. • The PI or facility supervisor receives a written report after the visit. • If there are deficiencies a reply with correction plan and completion date(s) is required.

35. Hints for Success • Contact OAW whenever you have questions regarding your use of animals, including when you may be unsure of whom to contact. • We will help you or refer you to the appropriate office or department.