Animal Care

1
Animal Care Use Programs in VA Research
James M. Trout, Ph.D.

• Office of
• Research
• Oversight

Human Subject Protection
Laboratory Animal Welfare
ORO
Research Laboratory Safety/Security
Research Misconduct
2
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
3
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
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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
5
VA Policies
VHA Handbooks 1200.1 1200.2 1200.7 1200.8 120
0.16 7701.1 1108.1 1108.2 (controlled
substances)
1200.7
www1.va.gov/vhapublications/publications.cfm?pub2
6
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
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Other Policies and Guidance
The Guide for the Care and Use of Laboratory
Animals The Guide 1996 (update
pending) Institute for Laboratory Animal
Research (ILAR) www.nap.edu/openbook.php?record_i
d5140pageR1 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?pageID216 Biosafety in Microbiological and
Biomedical Laboratories 5th Ed. 2007 The
BMBL Describes Animal Biosafety Levels for work
with pathogens www.cdc.gov/OD/ohs/biosfty/bmbl5/B
MBL_5th_Edition.pdf
5th Edition
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Other Policies and Guidance
NIH Guidelines for Research Involving Recombinant
DNA Molecules 2002 National Institutes of
Health If using rDNA in animals www4.od.nih.gov/
oba/rac/guidelines_02/NIH_Gdlnes_lnk_2002z.pdf OS
HA 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.
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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
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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
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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 MOUs
(Memorandum of Understanding) are Critical to
define roles and responsibilities Unique to
individual facilities
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Structure of ACUP
Institutional Official (IO) Attending
Veterinarian VMU Supervisor IACUC (Animal
Studies Subcommittee) The Research Development
Committee
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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
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The Veterinary Medical Officer VMO
Sometimes called the Attending Veterinarian dire
ct 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 PIs prior to protocol
submission Professional guidance and technical
support for animal activities
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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
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Institutional Animal Care and Use Committee
IACUC or the Animal Studies Subcommittee of the
RDC Existence and composition mandated by AWAR,
PHS Policy, 1200.7 Subcommittee of the
RDC RDC 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
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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
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IACUC Composition
One member must also be a member
of RDC SRS Optional members vice-chair anim
al facility (VMU) supervisor safety and health
personnel laboratory technicians second
unaffiliated member lay members alternates Adh
erence to required composition is critical only
a properly constituted IACUC can conduct
business A quorum (501) of VOTING members must
be present to conduct business
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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
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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
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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
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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 1st
and 2nd anniversary De Novo review prior to 3rd
anniversary
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Animal Use Protocols Review by IACUC
Two methods of review recognized by
regulations Full Committee Review FCR
Designated Member Review DMR
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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 Controversia
l 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
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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 PIs see the word
approval and start research
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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
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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
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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
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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
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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_t
o_Report_to_ORO_090805.doc
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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
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Resources

• VHA Handbooks
• www1.va.gov/vhapublications/publications.cfm?pub
  2
• The Guide
• www.nap.edu/openbook.php?record_id5140pageR1
• USDA APHIS (The Animal Welfare Act other
  information)
• www.aphis.usda.gov/animal_welfare/publications_an
  d_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/AnimalWelfareChecklis
  t-05-07-07.doc
• Scientists Center for Animal Welfare
• http//www.scaw.com/
• IACUC.org