Who Owns the Animals?

1
(No Transcript)
2
(No Transcript)
3
Who Owns the Animals?
Kathryn Bayne, M.S., Ph.D., D.V.M., DACLAM Senior
Director Director of Pacific Rim
Activities AAALAC International
4
Oversight authority

• OLAW
• USDA
• AAALAC International

• Follows the money trail
• Covered species on site
• Follows animal ownership

5
PHS Policy

• This Policy is applicable to all PHS-conducted
  or supported activities involving animals,
  whether the activities are performed at a PHS
  agency, an awardee institution, or other
  institution and conducted in the United States,
  Commonwealth of Puerto Rico, or any territory or
  possession of the United States.

6
USDA

• The Animal Welfare Act and accompanying Animal
  Welfare Regulations provide authority (as
  determined by the Secretary) for warm-blooded
  animals
• In research facilities, this includes live
  animals used or intended for use in research,
  testing, or experiments

7
(No Transcript)
8
AAALAC International

• All animals used or to be used in research,
  teaching or testing at accreditable units are to
  be included and evaluated. This includes
  traditional laboratory animals, farm animals,
  wildlife, and aquatic animals. Nontraditional
  animals, inclusive of invertebrate species, are
  also included where they are relevant to the
  unit's mission.

9
What does AAALAC visit?

• If your accredited institution owns animals at
  another accredited institution
• We will not include those animals in your site
  visit they will be addressed during the other
  institutions visit
• If your accredited institution owns animals at a
  non-accredited institution
• You will need to include those animals in your
  Program Description and we will include them in
  the site visit

10

• However, the accredited unit may have a more
  limited contract in which the accredited unit
  owns the animals. In this latter situation,
  AAALAC International considers those facilities
  to be an integral part of the institution's
  animal care program. The services and facilities
  provided by the contractual arrangement must be
  included in the application and annual reports,
  and the facilities will be visited as a part of
  the institution's original and periodic site
  visits to determine compliance with AAALAC
  International standards. Contractual agreements
  made by AAALAC International accredited
  institutions or applicants must provide for the
  inspection of the contracted facilities by AAALAC
  International site visit teams. If the contract
  facility is separately accredited by AAALAC
  International and is currently fully accredited,
  it will not be necessary to visit that facility
  during the site visit.

11
What does AAALAC visit?

• If your accredited institution is involved in a
  collaboration or contract (regardless if the
  performance site is accredited or not), but does
  not own the animals
• This does not need to be described in the Program
  Description, nor declared as part of your
  accredited unit

12

• Institutions may have contractual arrangements
  for certain aspects of their animal care
  activities with other animal care
  agencies/facilities. In some situations, an
  accreditable unit may issue a comprehensive
  contract whereby the contractor provides most or
  all specified facilities, services, personnel,
  animals, etc., and the animals are owned by the
  contractor. In this situation, AAALAC
  International accreditation does not extend to
  the contracted facilities and their associated
  animal care programs.

13
(No Transcript)
14
(No Transcript)
15
Defining ownership (Websters)

• Legal right of possession
• Lawful title to
• Proprietorship (legal title or exclusive right to
  some property)

16
Defining Ownership

• Shades of Grey

17
To define animal ownershipYou may need to get
the lawyers involved

• due to possibly varying state, municipal, and
  international laws regarding property ownership
  specific to your area

18
How to avoid confusion

• During the development of a contractual
  relationship, establish who owns the animals
  (e.g., authority for final disposition of an
  animal)
• If your institution is providing monetary support
  in a collaborative project, use of that money to
  purchase animals should be addressed up front

19
Animal Ownership? Intellectual Property
20
Animals at your institution that you dont own
but which may be reviewed by AAALAC

• Raptors in a rehab program owned by FWS, but used
  for teaching
• Client-owned animals in maintained in a vet
  school that are used in an IACUC approved protocol

21
Animals at your institution that you dont own
but which may be reviewed by AAALAC

• Agricultural animals whose primary purpose is
  other than teaching or research, but which are
  also used for either of those purposes
• Animal not owned by accredited unit, but housed
  in close proximity to those that are, and may
  impact well-being of the animals

22
Responsibility Accountability
23
Contracting Out Research to CROs What are the
Issues?
Wendy J. Underwood, D.V.M., M.S.,
DACVIM Director, Veterinary Services Eli Lilly
and Company
24
Introduction

• Pharmaceutical industry is under increasing
  pressure
• Increasing federal regulations and guidelines
• Increasing costs to deliver new molecular
  entities
• As a result, research institutions are evaluating
  and utilizing contract research organizations
  (CROs)

25
Issues

• Developing an outsourcing strategy
• Identifying and evaluating CROs
• Developing policies and procedures for oversight
  and approval of outsourced studies
• Identifying ongoing outsourced activities
• Assuring regulatory compliance
• Identifying the level of institutional oversight
  necessary for contracted animal work

26
Strategies and procedures

• Utilize only well-established CROs with proven
  records of success that are AAALAC accredited
• Utilize only local CROs so that investigators can
  oversee studies
• Utilize CROs with expertise in certain areas
• Utilize regional CROs with potential research and
  business synergies

27
Who drives the process?

• Investigator driven
• Portfolio driven
• Management driven

28
Each institution should develop its own strategy,
understand its own strategy, and communicate that
strategy prior to launching major outsourcing
efforts.
29
Initial steps

• Establish a centralized process for outsourced
  study approval and management
• Establish a process for veterinary and management
  approval
• Ensure proper provision for research animals
• Ensuring there is an alignment with business
  goals and objectives

30
Identify key internal resources

• Routing of study protocols
• Initial contact of potential CROs
• Scheduling of appropriate internal meetings
• Coordination of CRO communications
• Development of Statements of Work, purchase
  orders, and legal contracts

31
Identify a legal gatekeeper

• Trade secret information
• Proprietary animal models
• Contracts
• Animal ownership
• Assurance that the CRO will comply
• Reporting of adverse events

32
Create a list of all on-going outsourced
activities

• Centralized database
• Identify approved CROs
• Track ongoing outsourced activities
• Identify CRO areas of expertise
• Develop agreed upon criteria for CROs

33
Develop policies for outsourced studies

• CRO approval criteria and process
• Expectations for meeting all local, state, and
  national regulations and guidelines
• Expectations for the level and extent of
  institutional oversight for contracted research
  including
• Ensuring local IACUC review of animal use
  protocols
• Ensuring that the 3 Rs have been addressed
• Ensuring that the use of alternatives have been
  addressed
• Ensuring that the minimum number of animals have
  been used
• Ensuring that duplication of studies has not
  occurred.
• Ensuring appropriate removal from study and
  euthanasia

34
Evaluating CROs

• Develop evaluation criteria for
• animal care and use program
• research program

35
Evaluation criteria

• Animal care and use program
• regulatory status
• IACUC activity
• veterinary program
• animal husbandry

36
Evaluation criteria

• Research program
• technical staff capabilities
• general capabilities
• data collection
• quality assurance programs
• records and record retention system

37
Specifics

• Develop detailed study protocols
• Clearly state the purpose of the study and study
  objectives
• Develop sample handling and transport procedures

38
Harmonization

• Determine if exact harmonization of veterinary
  care, surgical and animal husbandry procedures is
  needed between the CRO and the institution. This
  is critical for study success!

39
Harmonization details

• Specific surgical details
• Caging
• Bedding
• Water

40
Other considerations

• Pilot or parallel studies
• Ethical information (3Rs)
• ABSL 2 or 3

41
Monitoring

• Who will do the monitoring?
• Who will report adverse events?
• Who will oversee
• Data collection?
• Study reports?
• Final study package?
• Who has final study package approval?

42
Conclusions

• Dont abdicate responsibility for the oversight
  of animal welfare!
• Establish company policies and/or guidelines
• Develop accepted CRO criteria
• Evaluate CROs
• Develop a list of approved CROs
• Develop a veterinary and management approval
  process
• Complete thorough written contracts
• Detail study protocols
• Establish lines of communication
• Perform and validate pilot studies
• Develop a process for study monitoring

43
Contracting in Researchto Universities What
are the Issues?
Joseph N. Benoit, Ph.D. Dean, Graduate
School University of North Dakota
44
Contracts are partnerships

• An agreement between two or more parties to do or
  not do something

Contractee (University)

• Contractor
• (Industry)

45
Understanding the partnership

• The key to the successful partnership, however
  is the recognition on both sides that
  universities and industry have distinct missions.
  The mission of the university is the pursuit of
  knowledge for its own sake, the best-known
  strategy for innovation and the mission of
  industries is to make money for their
  stockholders, the best known strategy for
  economic progress. In some contexts, these two
  missions can lead to aims that are antithetical.
  In other contexts, both aims can be fulfilled in
  pursuing a common goal, with corresponding
  benefit to society.
• Zack W. Hall, Ph.D., The Academy and Industry
  A View Across the Divide. In Buying In or
  Selling Out? The Commercialization of the
  American University, D.G. Stein, Ed., Rutgers
  University Press, 2004

46
Contractor expectations

• The party awarded the contract will be able to
  provide the services requested. The contractor
  assumes that the contractee has the expertise and
  infrastructure to perform the work.
• Contractor also expects to own the product of the
  work conducted by the contractee.

47
Contractee views

• The contractee understands that they will conduct
  the work.
• The contractee understands that they will be paid
  for the work that is done.
• The contractee may not fully recognize that their
  ability to to conduct curiosity based research
  may be curtailed by the contract.

48
Universities are becoming more entrepreneurial

• Research generates
• Money
• Prestige
• Intellectual property

49
The publics perspective of the university
mission has changed

• In 1999, North Dakota leaders looked into the
  future and saw challenges and opportunities that
  required immediate action. They committed to
  taking the bold steps needed to improve the
  states economic and demographic picture. These
  leaders believed the North Dakota University
  System to be an integral part of expanding and
  diversifying the states economy and enhancing
  the quality of life for all North Dakotans. As a
  result, profound changes are taking place, many
  of which reflect the growing relationships
  between the NDUS and its many public and private
  partners.
• North Dakota University System

50
What are the issues associated with innovative
university partnerships?

• Oversight
• Regulatory Compliance
• Infrastructure
• Intellectual Property
• Curiosity Driven Research vs. Contract Driven
  Research
• Conflicts of Interest and Conflicts of Time

51
Oversight of animal care use

• Contractor or Contractee IACUC?
• Who owns the animals?
• Protocol review
• Search for alternatives?
• Pain Distress?
• Use of analgesia?
• Removal of animals from study?
• Who provides the veterinary care?
• Employee health and safety?
• Semiannual Review?

52
Regulatory compliance

• USDA
• Which organization is held accountable for
  deficiencies?
• Biohazardous Agents
• Which committee reviews and approves protocol?
• Pharmaceuticals with unknown properties?
• Infectious agents?
• Select agents?
• Radiation
• Who reviews?
• Who monitors?
• Who disposes?

53
Infrastructure

• Adequacy of infrastructure to support the
  contract
• Does the contractor verify that the
  infrastructure exists?
• Economic benefit to the contractee?
• Does the contractee overextend their
  infrastructure for financial gain?

54
Intellectual property

• Who owns the data?
• Where are the data stored and archived?
• Whose record retention policies govern data
  storage and archiving?
• What about tissue samples?
• Curiosity-driven research vs. contract-driven
  research
• Who owns the idea?
• Who owns subsequent ideas?
• Who benefits when new discoveries are made?

55
Academic integrity issues

• Conflict of interest
• Conflict of time

56
Successful contracts involve a complex balancing
act
57
Suggested reading

• Buying In or Selling Out? The Commercialization
  of the American Research University. Donald G.
  Stein, Ed., Rutgers University Press, 2004.
• The Creation of the Future The Role of the
  American University. Frank H. T. Rhodes, Cornell
  University Press, 2001.
• Universities in the Marketplace The
  Commercialization of Higher Education. Derek
  Bok, Princeton University Press, 2003.
• Science, Money and Politics Political Triumph
  and Ethical Erosion. Daniel S. Greenberg, The
  University of Chicago Press, 2001.
• The Uses of the University. 5th Edition. Clark
  Kerr, Harvard University Press, 2001.

58
Neutralizing Dual RegulationsAWRs vs. GLPs
Kathy Laber, D.V.M., M.S., DACLAM Professor Medica
l University of South Carolina
59
Good Laboratory Practices 21 CFR

• Implemented in the late 70s
• In response to the FDA receiving research that
  was poorly conducted
• Assure quality and integrity of the safety data
  conducted in nonclinical laboratory studies.
• GLPs originated without animal impact as a
  specific focus/concern

60
Nonclinical studies

• Part of FDA drug approval process
• Adequate pharmacology/ toxicology drug
  studies using laboratory animals or in vitro
• Supports that its reasonably safe to conduct
  clinical investigations
• Types of Studies
• Single/Repeat dose toxicity, Biocompatibility,
  Reproduction/Development, etc..

61
Animal Welfare Act CFR 7

• Implemented in mid sixties
• AWRs originated with focus on random origin dogs
  cats, facilities and sanitation
• Impact on was very limited in first 2 decades
• Impact exploded with1985 amendments
• Definition of the IACUC
• Definition of AV /Adequate Veterinary Care

62
Intended protocol focus

• GLP
• Study Conduct
• AWA
• Impact of Study on Animal Welfare

63
Critical Player for GLPsStudy director

• study director has overall responsibility for
  the technical conduct of the study..and
  represents the single point of study control
• Does NOT MEAN they may disregard AWA, AV, IACUC
• From 21 CFR Part 58

64
Critical player for AWAAttending veterinarian

• has authority for activities involving animals
• research facility shall assure that the attending
  veterinarian has appropriate authority to ensure
  the provision of veterinary care
• ..shall establish programs of adequate
  veterinary care that include
• daily observation of all animals to assess their
  health and well-being
• From 9 CFR Part 2

65
Regulatory language GLPs

• animals may be treated for disease or signs of
  disease provided that such treatment does not
  interfere with the study.
• diagnosis, authorization of treatment,
  description of treatment, and each date of
  treatment shall be documented
• SOPs written for handling of animals found
  moribund or dead during study
• From 21 CFR Part 58

66
Regulatory languageAWA

• Procedures that may cause more than momentary or
  slight pain or distress will
• Involve in their planning, consultation with the
  Attending Veterinarian..
• Animals that would otherwise experience severe or
  chronic pain or distress that cannot be relieved
  will be painlessly euthanized at the end of the
  procedure, or, if appropriate, during the
  procedure
• From 9 CFR Part 2

67
Missing language from both CFRs

• Useful discussion of End Points
• GLP driver- Evidence of Product Safety
• AWA driver- Alleviation of pain/distress
• Defined Interface between Study Director (PI) and
  Veterinarian
• Study Director (Tox Management) reports to FDA
  and hosts FDA audits
• Attending veterinarian leads reporting of animal
  use (by pain category) to USDA and hosts USDA
  inspections

68
Dueling CFRs

• Toxicologists and Vets may resort to the use of
  their regulations as hammer
• Type A personalities- difficult to resist the
  temptation to trump each other with higher
  authority for action/inaction

69
(No Transcript)
70
(No Transcript)
71
(No Transcript)
72
(No Transcript)
73
Failure to address spirit of GLPs

• Insufficient safety information to support
  clinical testing
• Repetition of studies and increased animal use
• Increased time to make important therapies
  available to the public
• Increased cost that is forwarded to public

74
Failure to address spirit of AWA

• Negative impact on animal
• Unrelieved animal care staff pain/distress
• Reportable incident to regulatory agencies
• USDA citation/fine
• Adverse public relationships

75
AAALACs perspective

• Goal is avoid /minimize distress and pain in
  concert with sound science
• References AWA
• Does NOT reference GLPs

76
AAALACs perspective

• ..Euthanasia occurred only after receiving
  permission from the study directorcontrary to
  principles of Guide-MUST ensure AV has necessary
  authority to ensure prompt euthanasia.

77
AAALACs perspective

• study director determined whether or not
  veterinary assessment should occur. The study
  control by the study director does not supersede
  the requirement to assess animals by the
  veterinary staff..attending veterinarian
  MUST..have the oversight authority for aspects of
  animal care and use

78
AAALACs perspective

• DEFFERED
• PROBATION
• INTENT TO REVOKE
• REVOKE

79
(No Transcript)
80
Solution to challenge

• TEAM APPROACH TO SAFETY STUDIES
• COMMUNICATE
• Avoid GLP (us) versus AWA (them) debate
• LEARN EACH OTHERS BUSINESS

81
Solution to challenge

• Pre-emptive strike critical to success
• Protocol development
• SOP development
• Study conduct
• Diagnosis or treatment is permitted as long as
  it does not interfere with study objective. If
  the treatment interferes, the animal can be
  removed.

82
(No Transcript)
83
(No Transcript)
84
Research Collaborations at Land Grant
Institutions What are the Issues?
Joseph R. Haywood, Ph.D. Professor and
Chairperson Department Pharmacology
Toxicology Michigan State University
85
Land grant institutions represent a special
challenge

• Agriculture- and animal science-based education
• Large numbers of undergraduate students
• Outreach efforts 4H Clubs, tours
• Wildlife and natural resources
• Many species of animals
• Diversity of funding sources

86
Institutional philosophy

• USDA Intellectual and Property Ownership
• AAALAC Control
• PHS Money
• Issues
• What are the standards of the institution?
• PHS assurance?

87
Scenarios

• Taking the bull by the horns
• Shared ownership of animals
• Snakes, Snakes, Snakes What a zoo?
• No ownership, but faculty involvement
• Follow the shells Where is the teaching animal?
• Informal or formal relationships with privately
  owned animals
• Production animals or teaching animals?

88
Scenarios

• Out-of-site, Out-of-mind
• Off-site farms
• Trans-state-genics
• Large animal transgenics maintained on a private
  farm
• Large animal antibody-production on a private farm

89
Scenarios

• Lab for Rent The mobile laboratory
• Lab ownership, but not animals
• Swimming with the fishes
• Studies with state-owned wildlife on campus and
  off campus

90
Other known scenarios

• Spay-neuter clinic
• Veterinary clinical studies on client-owned
  animals
• Blood donors
• Wildlife recovery ward

91
The power of communication

• Memoranda of Understanding
• Plan for Adequate Veterinary Care
• Protocol Review
• Others
• Disaster Plan
• Occupational Health concerns
• Training issues

92
Practical considerations

• Think logically and talk it through
• Dont create problems
• Not every laboratory has four walls and HVAC
• What would 60 Minutes ask me?

93
Names, locations, and species are changed to
protect the victims
94
International Research Contracts and
Collaborations InvolvingLaboratory Animals
Dennis M. Stark, D.V.M., Ph.D., DACLAM Executive
Director Veterinary Sciences Bristol-Myers
Squibb Pharmaceutical Research Institute
95
What are the issues?

• Good Science
• Appropriate Animal Care
• Regulatory Compliance
• Institutional Standing
• Planned Oversight

96
Why the concern about standards?

• Regulations
• Cultures
• Legal Codes
• Ethical Codes
• Language

97
Due diligence

• IACUC Review
• Legal Review
• Site Visits Pre/Ongoing
• Written Agreement

98
What needs to be clear?

• Study Design
• Animal Care
• Veterinary Care
• Intellectual property
• Roles

99
Contracts, agreements and memos of understanding

• Delineate who is responsible for what
• Regulations covering laboratory animal use
• Inspections/auditing defined/by whom
• Review of contract, institution program, and
  inspection reports
• Notice of all changes in accreditation and
  regulatory standing
• Protocol reviews

• Ownership of laboratory animals
• Animal and veterinary care
• Protect Intellectual Property
• Confidentiality provisions
• Security
• Data/Records/Samples

100
What can we learn from granting agencies?

• Public Health Service
• The National Institutes of Health
• National Science Foundation
• Department of Defense
• National Academies of Science
• U.S. Department of Agriculture
• Organization for Economic Cooperation and
  Development

101
NIH supported activities

• NIH will not make an award for research involving
  live
• vertebrate animals unless the applicant
  organization and all performance sites are
  operating in accordance with an approved Animal
  Welfare Assurance.
• Foreign organizations proposing activities
  involving
• vertebrate animals are required to comply with
  the PHS
• Policy or provide evidence that acceptable
  standards for the humane care and use of animals
  will be met.

102
Statement of Compliance with Standards for
Humane Care and Use of Laboratory Animals by
Foreign Institutions

• In reference to the Public Health Service Policy
  on Humane Care and Use of Laboratory Animals, it
  will comply with laws, regulations, and policies
  regarding humane care and use of laboratory
  animals of the jurisdiction in which the research
  will be conducted.
• This Institution is guided by the International
  Guiding Principles for Biomedical Research
  Involving Animals developed by the Council for
  International Organizations of Medical Sciences.
• This Institution acknowledges and accepts
  responsibility for the care and use of animals
  involved in activities covered by this Statement
  of Compliance.

103
International Guiding Principles for Biomedical
Research Involving Animals

• Basic Principles (XI)
• Special Provisions
• Acquisition
• Transportation
• Housing
• Environmental Conditions
• Nutrition
• Veterinary Care
• Records

• Monitoring
• Alternatives

104
Resources

• PHS Policy on Humane Care and Use of Laboratory
  Animals
• http//grants2.nih.gov/grants/olaw/references
  /PHSPolicyLab Animals.pdf
• NIH Grants Policy Statement http//grants1.nih.g
  ov/grants/policy/nihgps_2003/NIHGPS_Part5.htm_Toc
  54600087
• International Guiding Principles for Biomedical
  Research Involving Animals
• http//www.cioms.ch/1985_texts_of_guidelines.
  htm
• Application of the OECD Principles of GLP to the
  Organization and Management of Multi-Site
  Studies_ENV/JM/MONO(2002)9
• www.oecd.org/ehs/
• International Regulations
• http//www.aaalac.org/resources/international
  regs.cfm

105
Association For Assessment And Accreditation of
Laboratory Animal Care International
106
Thank you
A sincere thanks to the following who helped with
the preparation of this talk

• Kathryn Bayne (AAALAC)
• Denis Doyle (NIH-OLAW)
• Terrance Hawk (GlaxoSmithKline)
• Michael Kastello (sanofi-aventis)
• Hilton Klein (Merck)
• Dale Martin (sanofi-aventis)
• Timothy Morris (GlaxoSmithKline)
• Edward Mundy (NSF)

• Mary Newman (BMS)
• Mary Pat Nowack (NAS)
• Gregory Reinhard (Merck)
• James Swearengen (AAALAC)
• Robert Trotta (BMS)
• Axel Wolff (NIH OLAW)
• Joanne Zurlo (NAS-ILAR)

107
Contact AAALAC Internationalaccredit_at_aaalac.org
www.aaalac.org301.231.5353