# Presentation: 541751

## Animal Care & Use Programs in VA Research 

- Office of
-         Research
-                 Oversight

- Human
- Subject
- Protection

- Research
- Laboratory
- Safety/Security

- Research
- Misconduct

- Laboratory Animal
- Welfare

- ORO

- James M. Trout, Ph.D.

## Definitions

**Definitions**

**Animal per VHA Handbook 1200.7**
**	****“****any live vertebrate animal used or intended for use in ****	****research, research training, experimentation, or ****	****biological testing, or for a related purpose.”**
**Animal per Animal Welfare Act Regulations**
**	****“****any live or dead cat or dog, non-human primate, ****	****guinea pig, hamster, rabbit, or any other warm blooded ****	****animal which is being used, or is intended for use in ****	****research, teaching, testing, or experimentation.”**
**	**
**These are referred to as “Regulated Species”**

## Definitions

**Definitions**

**The AWAR excludes:**
**	****Birds**
**	****Rats of the genus *****Rattus***
***	*****Mice of the genus *****Mus***
**Bred for use in research**
**These are referred to as “Non-regulated Species”**
**Also excluded:**
**	****Horses not used for research**
**	****Other farm animals used for food & fiber**
**	****Livestock used for improving**
**	****	****- animal nutrition**
**	****	****- breeding**
**	****	****- management**
**	****	****- production efficiency**
**	****	****- food & fiber quality**
**Not excluded if used for biomedical research**

## Regulations & Policies

**Regulations & Policies**

**USDA – United States Department of Agriculture**
**	****Animal Welfare Act Regulations**
**	****Compliance mandated by law**
**	**
**OLAW – Office of Laboratory Animal Welfare**
**	****PHS (Public Health Service) Policy**
**	****Compliance typically required if PHS funds received**
**	****VA requires compliance regardless of funding**
**	****grants1.nih.gov/grants/olaw**

**www.aphis.usda.gov/animal_welfare/publications_and_reports.shtml**

## 1200.7

**VA Policies**

**VHA Handbooks**
**	****1200.1**
**	****1200.2**
**	****1200.7**
**	****1200.8**
**	****1200.16**
**	****7701.1**
**	****1108.1 & 1108.2 (controlled substances)**

**1200.7**

- www1.va.gov/vhapublications/publications.cfm?pub=2

## VA Policies

**VA Policies**

**VHA handbook 1200.7 – Use of Animals in Research**
**	****Describes principles and procedures that govern**
**	****research, testing and teaching activities involving **
**	****laboratory animals in the VA**
**Incorporates AWAR, PHS Policy, other guidelines and VA policies**

## Other Policies and Guidance

**	*****The Guide***** **
**	****1996 (update pending)**
**	****Institute for Laboratory Animal Research (ILAR)**
**	****www.nap.edu/openbook.php?record_id=5140&page=R1**
**The Guide for the Care and Use of Agricultural Animals **
**	****	****	****in Agricultural Research and Teaching**
**	*****The Ag Guide***
**	****1999**
**	****Federation of Animal Science Societies (FASS)**
**	****www.fass.org/page.asp?pageID=216**
**Biosafety in Microbiological and Biomedical Laboratories 5****th**** Ed.**
**	****2007**
**	*****The BMBL***
**	****Describes Animal Biosafety Levels for work with pathogens**
**	****www.cdc.gov/OD/ohs/biosfty/bmbl5/BMBL_5th_Edition.pdf**

**Other Policies and Guidance**

- 5th Edition

## Other Policies and Guidance

**	****2002**
**	****National Institutes of Health**
**	****If using rDNA in animals**
**	****www4.od.nih.gov/oba/rac/guidelines_02/NIH_Gdlnes_lnk_2002z.pdf**
**OSHA**
**	****Occupational Safety and Health Administration**
**	****Animal programa must implement OHSP**
**	****www.osha.gov/**
**AAALAC**
**	****Association for the Assessment and Accreditation **
**	****	****	****of Laboratory Animal Care International**
**	****“****AAALAC International is a private, nonprofit organization that promotes **
**	****the humane treatment of animals in science through voluntary **
**	****accreditation and assessment programs.”**

**Other Policies and Guidance**

## AAALAC –  www.aaalac.org

**AAALAC –  www.aaalac.org**

**Accreditation for VA animal facilities is MANDATORY**
**VACO maintains contract with AAALAC**
**3 year cycle **
**Letter of notification**
**Submission of Program Description**
**Site visit**
**Correction of deficiencies – if any**
**Evaluation by Council on Accreditation **
**Notification of accreditation status – hopefully Full Accreditation**
**Annual Reports must be submitted**

## Other Mandatory Items

**Other Mandatory Items**

**PHS Assurance**
**	****Required for VA facilities even if no PHS funding received**
**USDA Registration **
**	****Required if regulated species are used at facility**

## Important Note – VA-Affiliate Interactions

**Important Note – VA-Affiliate Interactions**

**Many Possible Scenarios**
**	****VA uses affiliate veterinarian **
**	****VA houses animals at affiliate**
**	****Affiliate houses animals in VA space**
**	****VA uses affiliate IACUC**
**	****VA covered by affiliate:**
**	****	****USDA registration, and/or**
**	****	****PHS assurance, and/or**
**	****	****AAALAC accreditation**
**MOU’s (Memorandum of Understanding) are:**
**	****Critical to define roles and responsibilities**
**	****Unique to individual facilities****	**

## Structure of ACUP

**Structure of ACUP**

**Institutional Official (IO)**
**	**
**Attending Veterinarian**
**VMU Supervisor**
**IACUC (Animal Studies Subcommittee)**
**The Research & Development Committee**

## The Institutional Official - IO

**The Institutional Official - IO**

**Ultimately responsible for compliance with law**
**– ****goes to jail person –**
**For VA facilities – the Medical Center Director**
**	****	**
**Issues letters of appointment for IACUC members**
**Point of contact for correspondence to/from outside organizations**
**If covered under affiliate PHS assurance or AAALAC accreditation ****	****– administrator at affiliate must assume the role of IO**
**If use affiliate IACUC, MCD and Affiliate IO must JOINTLY appoint ****	****IACUC members**

## The Veterinary Medical Officer – VMO 

**The Veterinary Medical Officer – VMO **

**Sometimes called the Attending Veterinarian**
**“****direct or delegated authority and responsibility for activities involving animals” **
**	**
**Experience with laboratory animals**
**	**
**Voting member of IACUC**
**Drafting/reviewing regulatory documents**
**	****AAALAC program description**
**	****PHS assurance**
**	****USDA annual reports**
**	****VA VMU annual report**
**Consultation with PI’s prior to protocol submission**
**Professional guidance and technical support for animal activities**

## VMU Supervisor (and staff)

**VMU Supervisor (and staff)**

**Responsible for operation of the animal research facility (ARF)**
**Handles day to day operations, animal husbandry**
**Develops SOP manual for ARF**
**Maintains essential records**
**Supervised or directed by VMO**

## Institutional Animal Care and Use Committee

**Institutional Animal Care and Use Committee**

**IACUC or the Animal Studies Subcommittee of the R&DC**
**Existence and composition mandated by AWAR, PHS Policy, 1200.7**
**Subcommittee of the R&DC**
**	****R&DC: **
**	****     ****evaluates IACUC function**
**	****     ****ensures appropriate composition**
**	****     ****assists in identifying nominees for appointment by IO**
**	****     ****reviews IACUC minutes**
**	**
**Charged with oversight of animal research**
**	****oversees all aspects of the ACUP**
**Facility can use IACUC of affiliate or another medical center**
**	****	****VMO/VMC & VA Scientist must serve on committee**
**	****	****MOU**

## IACUC Composition

**IACUC Composition**

**Members appointed in writing by IO (MCD) for specific terms**
**	****	****chair – 1 year, renewable**
**	****	****other members – 3 years, renewable**
**Ex officio members**
**	****voting OR non-voting**
**	****no length of term**
**	****eg: VMO is an ex officio voting member**
**Minimum of 5 voting members**
**	****chair**
**	****AV**
**	****scientist involved in animal research**
**	****lay member – not involved in animal research**
**	****unaffiliated member – no affiliation with **
**	****	****facility other than service on IACUC Veterans ****	****	****who volunteer at or receive medical care from ****	****	****the facility are not “unaffiliated”**

## IACUC Composition

**IACUC Composition**

**One member must also be a member of:**
**	****R&DC**
**	****SRS**
**Optional members**
**	****vice-chair**
**	****animal facility (VMU) supervisor **
**	****safety and health personnel**
**	****laboratory technicians**
**	****second unaffiliated member & lay members**
**	****alternates**
**Adherence to required composition is critical**
**	****only a properly constituted IACUC can conduct business**
**A quorum (50%+1) of VOTING members must be present to conduct business**

## IACUC Functions

**IACUC Functions**

**Ensure compliance with regulations and policies**
**Establish internal (facility specific) polices**
**Protocol review & approval**
**Continuing review of protocols – annually**
**Review and approval of amendments**
**Compliance monitoring (post approval monitoring)**
**Semi-annual program review & facility inspection**
**Review and verification of training, including IACUC members**
**Write and publish minutes within 3 weeks of meeting date**

## IACUC Functions

**IACUC Functions**

**Investigate animal care/non-compliance complaints**
**Suspend research activities involving animals**
**Correspond (through the IO) with regulatory agencies**
**Ensure adherence to occupational health and safety regulations **
**	****	****by personnel working with animals**
**Risk assessments of personnel working with animals or **
**	****	****entering the animal research facility**
**Review and verify accuracy of:**
**	****USDA Annual Report**
**	****PHS Assurance and annual update**
**	****AAALAC Program Description**
**	****Annual VMU Report**

## Semi-annual Program Review & Facility Inspection

**Semi-annual Program Review & Facility Inspection**

**Performed every 6 months – longer intervals can result in citation**
**Not just a facility walkthrough**
**Programmatic elements MUST be evaluated**
**Must review IACUC records for 5% (minimum of 5) of active protocol**
**Who?**
**	****At least 2 IACUC members**
**	****No member can be excluded**
**	****Ad hoc consultant may be invited**
**How?**
**	****Sample program review checklist**
**	****	****grants1.nih.gov/grants/olaw/sampledoc/chek1a.htm**
**	****Sample facility inspection checklist**
**	****	****grants1.nih.gov/grants/olaw/sampledoc/chek2a.htm**
**	****Sample report to IO**
**	****	****grants1.nih.gov/grants/olaw/sampledoc/iosamp.htm**

## Animal Use Protocols

**Animal Use Protocols**

**ACORP – Animal Component of Research Protocol**
**ALL research animals at must be covered under a protocol**
**Describes in detail the work to be done**
**NO animal work can begin prior to approval**
**NO changes to protocol except by submission of amendment**
**Valid for a period of 3 years**
**Continuing review (annual review) at 1****st**** and 2****nd**** anniversary**
***De Novo***** review prior to 3****rd**** anniversary**

## Animal Use Protocols – Review by IACUC

**Animal Use Protocols – Review by IACUC**

**Two methods of review recognized by regulations**
**	**
**	****	****Full Committee Review – FCR **
**	****	****Designated Member Review – DMR **

## Animal Use Protocols – Full Committee Review 

**Animal Use Protocols – Full Committee Review **

**Conducted at a convened meeting by a quorum of members**
**“****Conflicted” members CANNOT contribute to quorum**
**In practice much preliminary work can occur prior to meeting**
**Why FCR?**
**	****invasive procedures**
**	****Pain & distress category**
**	****Controversial – eg: death as an endpoint**
**	****Request to deviate from regulations**
**Possible outcomes – by vote of simple majority**
**	****Approve**
**	****Require modifications to secure approval**
**	****Table – pending major revisions**
**	****Withhold approval**

## Animal Use Protocols – Full Committee Review 

**Animal Use Protocols – Full Committee Review **

**What about...**
**	****approved pending changes**
**	****conditional approval**
**	****provisional approval**
**	****approved pending clarifications**
**AVOID these categories**
**Not recognized in the regulations**
**PI’s see the word approval and start research**

## Animal Use Protocols – Full Committee Review 

**Animal Use Protocols – Full Committee Review **

**Final approval for categories:**
**	****Require modifications to secure approval**
**	****Table protocols**
**Vote at next convened meeting after receipt of changes**
**Committee agrees to change to DMR**
**	**

## Animal Use Protocols – Designated Member Review 

**Animal Use Protocols – Designated Member Review **

**NOT expedited review**
**Chair designates one (or more) members to review protocol**
**Full committee has opportunity to read protocol and any ****	****member can call for FCR**
**Not less stringent than FCR**
**Possible outcomes**
**	****approval**
**	****request modifications to secure approval**
**	****refer to full committee**
**	****DMR cannot withhold approval**
**DMR committee cannot approve by majority vote**
**Dissent by any DMR committee member results in automatic ****	****referral to full committee**
**	**

## Protocol Review

**Protocol Review**

**What is Administrative Review?**
**Neither AWAR or PHS policy uses this term**
**Used for *****minor***** changes in approved protocols (amendments)**
**IACUC determines minor changes **
**Establish SOP for administrative review**
**Document in PHS assurance**
**	**

## Protocol Review – Critical Considerations

**Protocol Review – Critical Considerations**

**Investigator/staff training**
**Justification of species**
**Justification of animal numbers**
**Animal sources**
**Pain & distress categories**
**Alternatives search – especially for Cat D & E**
**Surgery, anesthesia, analgesia**
**Requests to deviate from standard of care/housing**
**Death as an endpoint**
**Euthanasia****	**

## Reporting Requirements 

**Reporting Requirements **

**Findings of non-compliance should be self-reported**
**USDA – if regulated species are involved**
**OLAW**
**AAALAC**
**ORD**
**ORO**
**     ****See: *****What to report to ORO***** **
**     ****www1.va.gov/oro/docs/What_to_Report_to_ORO_090805.doc**
**	**

## Common Inspection Findings

**Common Inspection Findings**

**Improperly constituted IACUC**
**Failure to conduct/document semi-annual program and facility review **
**Semi-annual does not include a review of 5% of active protocols**
**Semi-annual report not sent to IO**
**Failure to implement occupational health and safety program **
**Inadequate/undocumented training: IACUC members, investigators, caretakers**
**NO SOP Manual**
**No disaster plan**
**Lack vermin/pest control**
**Failure to report violations to outside groups **
**Inadequate review of Category D and E protocols **
**Inadequate post-surgical care, monitoring, & analgesia**
**Use of outdated and/or non-pharmaceutical grade drugs **
**Inadequate tracking and securing of controlled substance**
**Inadequate record-keeping**
**Insufficient justification for number of animals requested**
**Inadequate alternative searches**
**Implementation of unapproved protocol changes**
**Insufficient post approval monitoring**
**Failure to conduct annual overheat test**

## VHA Handbooks
	www1.va.gov/vhapublications/publications.cfm?pub=2
The Guide 
	www.nap.edu/openbook.php?record_id=5140&page=R1
USDA APHIS (The Animal Welfare Act & other information)
	www.aphis.usda.gov/animal_welfare/publications_and_reports.shtml
OLAW (PHS Policy  & other information)
	http://grants1.nih.gov/grants/olaw/
NIH Guidelines for Research Involving Recombinant DNA Molecules
	http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Gdlnes_lnk_2002z.pdf
OSHA
	www.osha.gov 
AAALAC
	www.aaalac.org
ORO Animal Welfare Checklist
	http://www1.va.gov/oro/docs/AnimalWelfareChecklist-05-07-07.doc
Scientists Center for Animal Welfare
	http://www.scaw.com/ 
IACUC.org
	http://www.iacuc.org/ 
American Association for Laboratory Animal Science
	http://www.aalas.org/index.aspx 
PRIM&R - Public Responsibility in Medicine and Research
	http://www.primr.org/ 
AVMA Guidelines on Euthanasia 
	http://www.avma.org/issues/animal_welfare/euthanasia.pdf 
IACUC Guidebook
	 http://grants1.nih.gov/grants/olaw/guidebook.pdf
ALT Web – Information on alternatives to animal testing
	http://altweb.jhsph.edu/ 
NIH Bioethics Resources on the Web – many links
	http://bioethics.od.nih.gov/animals.html 

- 	_[www1.va.gov/vhapublications/publications.cfm?pub=2](http://www1.va.gov/vhapublications/publications.cfm?pub=2)_
- The Guide
- 	_[www.nap.edu/openbook.php?record_id](http://www.nap.edu/openbook.php?record_id=5140&page=R1)__[=5140&page=R1](http://www.nap.edu/openbook.php?record_id=5140&page=R1)_
- USDA APHIS (The Animal Welfare Act & other information)
- 	_[www.aphis.usda.gov/animal_welfare/publications_and_reports.shtml](http://www.aphis.usda.gov/animal_welfare/publications_and_reports.shtml)_
- OLAW (PHS Policy  & other information)
- 	_[http://grants1.nih.gov/grants/olaw/](http://grants1.nih.gov/grants/olaw/)_
- NIH Guidelines for Research Involving Recombinant DNA Molecules
- 	_[http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Gdlnes_lnk_2002z.pdf](http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Gdlnes_lnk_2002z.pdf)_
- OSHA
- 	_[www.osha.gov](http://www.osha.gov/)_
- AAALAC
- 	_[www.aaalac.org](http://www.aaalac.org/)_
- ORO Animal Welfare Checklist
- 	http://www1.va.gov/oro/docs/AnimalWelfareChecklist-05-07-07.doc
- Scientists Center for Animal Welfare
- 	http://www.scaw.com/
- IACUC.org
- 	http://www.iacuc.org/
- American Association for Laboratory Animal Science
- 	http://www.aalas.org/index.aspx
- PRIM&R - Public Responsibility in Medicine and Research
- 	http://www.primr.org/
- AVMA Guidelines on Euthanasia
- 	http://www.avma.org/issues/animal_welfare/euthanasia.pdf
- IACUC Guidebook
- 	 http://grants1.nih.gov/grants/olaw/guidebook.pdf
- ALT Web – Information on alternatives to animal testing
- 	http://altweb.jhsph.edu/
- NIH Bioethics Resources on the Web – many links
- 	http://bioethics.od.nih.gov/animals.html

**Resources**