Survey of Regulatory Documents

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Survey of Regulatory Documents
Another flaw in the human character is that
everybody wants to build and nobody wants to do
maintenance. Kurt Vonnegut (1922 - ), Hocus Poc
us
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Law vs. Regulations vs. Guidance
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USDA is King

• Most important agency regulating animal
  research is the United States Department of
  Agriculture (USDA).
  
• Congress gave the USDA broad authority to
  regulate animal research in the Animal Welfare
  Act.
  
• USDA established Animal Welfare Act Regulations
  (AWAR), which take precedence over regulatory
  documents produced by all other agencies.
  
• The USDA has published a Policy Manual that
  clarifies how some of the language in the USDA
  Animal Welfare Act Regulations should be
  interpreted.

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Animal Care

• The Animal Care office in the Animal and Plant
  Health Inspection Service at USDA administers the
  AWAR

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Animal Welfare Act
USDA Animal Welfare Act Regulations
Part 2 Regulations
Part 3 Standards
Part 1 Def of Terms
Definitions 1.1
Subpart A Licensing- 2.1-2.11
Subpart B Registration- 2.25-2.27
Subpart C Research Facilities- 2.30-2.38
Subpart D Veterinary Care (exhibitors)- 2.40
Subpart E ID of Animals- 2.50-2.55
Subpart F Stolen Animals- 2.60
Subpart G Records- 2.75-2.80 Subpart H Compl wit
h Stds/Holding Periods- 2.100-2.102
Subpart I Miscellaneous 2.125-2.133
Subpart A Dogs and Cats - 3.1-3.19
Subpart B Guinea Pigs and Hamsters- 3.25-3.41
Subpart C Rabbits- 3.50-3.66 Subpart D Nonhuman
Primates- 3.75-3.92 Subpart E Marine Mammals-
3.100-3.118 Subpart F Other Warm-Blooded Animals
- 3.125-3.142
Guidance Policy Manual Policies 1-29
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Lab Mice and Rats are Not Regulated by USDA

• "Animal means any live or dead dog, cat, nonhuman
  primate, guinea pig, hamster, rabbit, or any
  other warm blooded animal, which is being used,
  or is intended for use for research, teaching,
  testing, experimentation, or exhibition purposes,
  or as a pet. This term excludes Birds, rats of
  the genus Rattus and mice of the genus Mus bred
  for use in research, and horses not used for
  research purposes and other farm animals, such
  as, but not limited to livestock or poultry used
  or intended for use for improving animal
  nutrition, breeding, management, or production
  efficiency, or for improving the quality of food
  or fiber. With respect to a dog, the term means
  all dogs, including those used for hunting,
  security, or breeding purposes." (USDA AWAR Part
  1, Definitions)

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Public Health Service (PHS) Policy

• PHS Policy on Humane Care and Use of Laboratory
  Animals (PHS Policy) incorporates compliance
  with the USDA AWAR.
  
• Congress gave PHS authority to regulate animal
  research at its awardees in the Health Research
  Extension Act of 1985.
  
• PHS Policy is functionally equivalent to USDA
  regulations.
  
• OLAW provides written guidance that clarifies
  PHS Policy, equivalent to USDA Policy Manual.
  
• PHS insiders refer to PHS Policy as the PHS
  Policy.

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Office of Laboratory Animal Welfare

• The Office of Laboratory Animal Welfare at NIH
  administers PHS Policy

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Health Research Extension Act of 1985
PHS Policy on Humane Care and Use of Lab Animals
U.S. Govt Principles for Utilization and Care of
Vertebrate Animals Used in Testing, Research, and
Training
Main Body
Guide for the Care and Use of Laboratory Animals
Report of the AVMA Panel on Euthanasia
I. Introduction II. Applicability III. Defini
tions IV. Implementation by Institutions A.
Animal Welfare Assurance B. Functions of th
e Institutional Animal Care and Use Committee
C. Review of PHS-Conducted or Supported
Research Projects D. Information Required in
Apps and Proposals Submitted to PHS
E. Recordkeeping Requirements
F. Reporting Requirements
V. Implementation by PHS A. Responsibilities
of the Office of Laboratory Animal Welfare
B. Responsibilities of PHS Awarding Units
C. Conduct of Special Reviews/Site Visits
D. Waiver
Guidance OLAW Letters and Articles
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PHS Policy Definition of Animal

• "Animal- Any live, vertebrate animal used or
  intended for use in research, research training,
  experimentation, or biological testing or for
  related purposes." (PHS Policy, Section III.A)
• Covers lab rodents, but only live ones.

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US Government Principles- IRAC, 1980s

• Part of PHS Policy. Critical concepts for
  IACUC reviewers.

I. The transportation, care, and use of animals
should be in accordance with the Animal Welfare
Act (7 U.S.C. 2131 et. seq.) and other applicable
Federal laws, guidelines, and policies.
II. Procedures involving animals should be desig
ned and performed with due consideration of their
relevance to human or animal health, the
advancement of knowledge, or the good of society.
Justification for Use of Animals
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III. The animals selected for a procedure should
be of an appropriate species and quality and the
minimum number required to obtain valid results.
Methods such as mathematical models, computer
simulation, and in vitro biological systems
should be considered. IV. Proper use of animals
, including the avoidance or minimization of
discomfort, distress, and pain when consistent
with sound scientific practices, is
imperative. Unless the contrary is established,
investigators should consider that procedures
that cause pain or distress in human beings may
cause pain or distress in other animals.
Alternatives- the 3 Rs
Philosophy of IACUC Pain/Distress Evaluation
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V. Procedures with animals that may cause more
than momentary or slight pain or distress should
be performed with appropriate sedation,
analgesia, or anesthesia. Surgical or other painf
ul procedures should not be performed on
unanesthetized animals paralyzed by chemical
agents. VI. Animals that would otherwise suff
er severe or chronic pain or distress that cannot
be relieved should be painlessly killed at the
end of the procedure or, if appropriate, during
the procedure.
Sole Use of Paralytics Prohibited
Need for Endpoint Criteria
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VII. The living conditions of animals should be
appropriate for their species and contribute to
their health and comfort. Normally, the housing,
feeding, and care of all animals used for
biomedical purposes must be directed by a
veterinarian or other scientist trained and
experienced in the proper care, handling,
and use of the species being maintained or
studied. In any case, veterinary care shall be
provided as indicated. VIII. Investigators and
other personnel shall be appropriately qualified
and experienced for conducting procedures on
living animals. Adequate arrangements shall be
made for their in-service training, including the
proper and humane care and use of laboratory
animals.
Veterinary Care Required
Training Required
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IX. Where exceptions are required in relation to
the provisions of these Principles, the decisions
should not rest with the investigators directly
concerned but should be made, with due regard to
Principle II justification for animal use, by
an appropriate review group such as an
institutional animal care and use committee. Such
exceptions should not be made solely for the
purposes of teaching or demonstration.
IACUC Review and Oversight Needed
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VA Programs Follow USDA AWAR and PHS Policy

• Federal law requires VA animal research
  programs to comply with USDA Animal Welfare Act
  Regulations (Animal Welfare Act, item 2(e)),
  reiterated in 1200.7, item 4b(5))
• VHA Handbook 1200.7 (Use of Animals in
  Research) stipulates that VA programs follow PHS
  policy whether or not PHS funds are utilized
  (1200.7, item 4b(4))

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VA Policy- 1200.7, Use of Animals in Research

• Equivalent to USDA regulations but without
  criminal penalties.
  
• Similar to PHS Policy- to get PHS funds, PHS
  Policy must be followed to get VA funds, VA
  Policy must be followed.
  
• Philosophy of VA Policy USDA and PHS provide
  adequate framework for animal research
  additional VA policies only needed to address
  gaps or consistent problems in VA programs.

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VA Authorizing Legislation Title 38 United
States Code (U.S.C.) Section 7303
VHA Handbook 1200.7, Use of Animals in Research
Appendix A CVMO Contact Info
Appendix B Special Aged Rodent Procurement
Appendix C Occupational Health and Safety
Appendix D Animal Component of Research Protocol
(ACORP)
Appendix E VA IACUC Semi-Annual Self-Review Item
s
Sections 1. Purpose 2. Background 3. Def
initions 4. Scope 5. Chief Veterinary Medic
al Officer (CVMO) VA Central Office
6. Organization at VA Medical Centers
7. VMU Operations at the VA Medical Center
8. Institutional Animal Care and Use Committees
9. Visits to VA Animal Facilities by Non-VA Fe
deral Regulators 10. Occupational Health and Safe
ty 11. References
Main Body
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Association for Assessment and Accreditation of
Laboratory Animal Care, International (AAALAC)
Rules of Accreditation

• Participation in AAALAC program is voluntary for
  most of the world, but mandatory for VA programs.
  (1200.7, item 7e)
  
• ORD pays for a contract that covers all VA
  programs. (1200.7, item 7e)
  
• All accredited programs must agree to follow
  AAALACs rules.

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Office of Res Oversight (ORO) and Office of Res
and Development (ORD)- Missions
Secretary of the VA
Undersecretary for Health
Network/VISNs
ORD
ORO
Developing Policy, Funding Research
Monitoring Research Compliance
Performing and Supporting Research
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ORO and ORDAnimal Research Policies
Secretary of the VA
Undersecretary for Health
Network/VISNs
ORD
ORO
1200.7, Use of Animals in Research
Memo- What to Report to ORO
(VISN Research Policies)
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Memo- What to Report to ORO, September 8, 2005

• Page 2, item 4 Stipulates format of deficiency
  reports
  
• Pages 3-4 12 types of animal research
  deficiencies that must be reported to ORO

Note Handbook 1200.7, paragraph 8g and
subparagraphs, has additional guidance on what
must be reported, how it should be reported, and
who should be notified.
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Memo- What to Report to ORO, September 8, 2005

• Note VHA Handbook 1058.1 (November 19, 2004)
  entitled "Reporting Adverse Events In Research to
  The Office of Research Oversight" addresses only
  reporting requirements for human subjects
  research programs.

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ORO/OLAW Documents

• ORO has an agreement with OLAW (PHS Policy) to
  share information.
  
• Item IV.B The cooperating agencies agree to
  share information, to the extent permitted by
  law, of mutual concern and interest regarding
  animal welfare at VA and VA-affiliated PHS
  assured institutions, including, but not limited
  to, evidence of serious noncompliance with
  standards for the care and use of laboratory
  animals, significant adverse findings regarding
  animal care and use investigated, inspected, or
  site-visited, and actions taken by the agencies
  in response to the findings.

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Shared Compliance Information

• VA ORO has an agreement with OLAW
• USDA and OLAW have an agreement with FDA

Conceal a flaw, and the world will imagine the
worst. Marcus Valerius Martialis (Latin poet 40
AD-103 AD)
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Managing Regulatory Complexity is Difficult
Some Strategies

• Design forms (ACORP , semi-annual review forms)
  and SOPs to help investigators, IACUC Tab U,
  and animal care staff meet regulatory
  expectations.
• Provide training so that forms and SOPs can be
  used effectively.
  
• Use software to manage tasks of tracking protocol
  expiration dates, tracking animal use, generating
  correspondence, agendas and minutes, and
  generating standard regulatory reports.