Title: Who Owns the Animals?
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3Who Owns the Animals?
Kathryn Bayne, M.S., Ph.D., D.V.M., DACLAM Senior
Director Director of Pacific Rim
Activities AAALAC International
4Oversight authority
- OLAW
- USDA
- AAALAC International
- Follows the money trail
- Covered species on site
- Follows animal ownership
5PHS 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.
6USDA
- The Animal Welfare Act and accompanying Animal
Welfare Regulations provide authority (as
determined by the Secretary) for warm-blooded
animals - In laboratory animal programs, this includes live
animals used or intended for use in research,
teaching, testing, or experiments
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8AAALAC 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.
9What 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.
11What 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.
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15Defining ownership (Websters)
- Legal right of possession
- Lawful title to
- Proprietorship (legal title or exclusive right to
some property)
16Defining Ownership
17To 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
18How 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
19Animal Ownership? Intellectual Property
20Animals 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
21Animals 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
22Responsibility Accountability
23Contracting OutWhat are the Issues?
Wendy J. Underwood, DVM, MS, DACVIM Director,
Veterinary Resources Eli Lilly and Company
24Introduction
- 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)
25Issues
- Developing an outsourcing strategy
- Identifying, evaluating and approving 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
26Strategies 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
27Who drives the process?
- Investigator driven
- Portfolio driven
- Management driven
28Each institution should develop its own strategy,
understand its own strategy, and communicate that
strategy prior to launching major outsourcing
efforts.
29Initial steps
- Establish a centralized process for outsourced
study approval and administrative management - Establish a process for veterinary and management
approval - Ensure proper provision for research animals
- Ensure alignment with business goals and
objectives
30Identify key internal resources
- Routing of study protocols and contracts
- Initial contact of potential CROs
- Scheduling of appropriate internal meetings
- Coordination of CRO communications
- Development of Statements of Work, Purchase
Orders, and legal contracts
31Identify a legal gatekeeper
- Trade secret information
- Proprietary animal models
- Contracts should be detailed
- Ownership of animals
- Assurance that the CRO will comply
- Reporting of adverse events
32Centralized database
- List approved CROs
- Identify CRO areas of expertise
- List all outsourced activities
- Track ongoing outsourced activities
33The institution should develop policies for
outsourced studies!
- CRO approval criteria
- Expectations for meeting all local, state, and
national regulations and guidelines - Expectations for the level and extent of
institutional oversight including - Ensuring 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
34Evaluating CROs
- Develop evaluation criteria for
- animal care and use program
- research program
35Evaluation criteria
- Animal care and use program
- regulatory status
- veterinary program
- animal husbandry
- physical plant
- security
36Evaluation criteria
- Research program
- organizational structure
- technical staff capabilities
- general research capabilities
- data collection methods and capabilities
- quality assurance programs
- records and record retention systems
37CRO specialties
- Surgical models
- surgeon qualifications
- number and location of surgical sites
- surgeon turnover and training
- Breeding programs
- genetic integrity
- record keeping and animal tracking
- biosecurity and veterinary care
- security and transportation
38Many issues arise, but can be addressed!
- Develop detailed study protocols
- Clearly state the purpose of the study and study
objectives - Develop sample handling and transport procedures
39Harmonization
- 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!
40Harmonization details
- Health status
- Veterinary program
- Specific surgical details
- Husbandry
- Caging
- Bedding
- Water
41Other considerations
- Pilot or parallel studies
- Ethical information (3Rs)
- Biosafety ABSL level 2 or 3?
42Monitoring
- 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?
43An informal survey was done for benchmarking
purposes
- Went to COMPMED, Council, colleagues
- 32 responses
44Question 1 What type of contracting organization
- 14 private
- 11 pharma (6-disc 4-disc/tox 1-ASR)
- 3 biotech
- 18 public
- 4 were vet schools
- 12 were universities
- 1 was a hospital
- 3 mixed
-
45Q2 Asked if profit, nonprofit, AAALAC, USDA,
etc.
- 24/32 were AAALAC Accredited
- 28/32 were USDA registered
- 20/32 were PHS Assured
- 30/32 had an IACUC
- Indicates general compliance
- Contractors can use this information
46Q3 Is the process official?
- 14/32 had an official process
- 13/32 had an unofficial process
- 5/32 had no process
47Q4 What did the formal approval process include?
- 2/32 said a thorough process was created and
required a site visit, but 7/32 said the process
could be better - Other
- 4-AAALAC, 5-PHS 7-USDA
- 6-9 policy/guideline based
- Tox units required official visits and AAALAC
Accreditation
48Q5 What did the informal process include?
- 6/32 req AAALAC 18 prefer, 3 dont
- 16/32 req USDA 3 prefer, 3 dont
- 11/32 req PHS 4 prefer 4 dont
- 7/32 req GLP 6 prefer 7 dont
- Private sector puts more emphasis on USDA and
GLP, while public sector puts more emphasis on
USDA and PHS.
49Q6 What official paperwork is required?
- 6/32 said none
- 10/32 said official IACUC approval letters by
both institutions! 9/32 were from Private
sector!) - So, institutions do require some paperwork, and
the public sector usually requires IACUC
documentation.
50Q7 If concerned about differing standards for
ACU.
- 13/14 for-profit said Yes
- 8/18 not-for-profit said Yes
- Implies general concern for differing standards
for animal care and use.
51Q8 Who coordinates contracted studies?
- 27/32 had an over sight program
- 9/32 said Lab Animal Management
- 8/32 said Research Management
- 10/32 said other, IACUC
- So, a variety of organizational units
administrate contracted studies.
52Q9 Is the unit moving toward a more official
process?
- 18/32 said Yes!
- 12/14 for-profit private institutions said
Yes - 6/18 not-for-profit public said Yes
- Interesting! For-profit units also indicated
(Q7) concern about differing standards.
53Q10 Does lab animal management know the total
number of studies contracted?
- 14/32 said Yes
- 9/18 not-for-profit said Yes
- 5/14 for-profit said Yes
54Q 11 Does the IACUC know the number and type of
studies outsourced?
- 15/32 said Yes
- 3/14 of for-profit said Yes
- 12/18 of not-for-profit said Yes
- Interesting contrast!
55Conclusions
- Dont abdicate responsibility for the oversight
of animal welfare! - Establish company policies and/or guidelines
- Develop database of approved CROs
- Establish an institutional approval process for
outsourced studies
56Conclusions (contd)
- Develop thorough written contracts
- Create detailed study protocols
- Perform and validate pilot studies
- Establish lines of communication
- Develop a process for study monitoring
57Contracting in Researchto Universities What
are the Issues?
Joseph N. Benoit, Ph.D. Dean, Graduate
School University of North Dakota
58Contracts are partnerships
- An agreement between two or more parties to do or
not do something
Contractee (University)
59Understanding 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
60Contractor 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.
61Contractee 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.
62Universities are becoming more entrepreneurial
- Research generates
- Money
- Prestige
- Intellectual property
63The 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
64What 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
65Oversight 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?
66Regulatory 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?
67Infrastructure
- 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?
68Intellectual 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?
69Academic integrity issues
- Conflict of interest
- Conflict of time
70Successful contracts involve a complex balancing
act
71Suggested 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.
72Neutralizing Dual RegulationsAWRs vs. GLPs
Kathy Laber, DVM, MS, DACLAM Professor Medical
University South Carolina
73Good 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
74Nonclinical 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..
75Animal Welfare Act CFR 7
- Implemented in mid sixties
- AWRs originated with focus on random origin dogs
cats, facilities and sanitation - Impact was very limited in first 2 decades
- Impact exploded with1985 amendments
- Definition of the IACUC
- Definition of AV /Adequate Veterinary Care
76Intended protocol focus
- GLP
- Study Conduct
- AWA
- Impact of Study on Animal Welfare
77Critical 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
78Critical 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
79Regulatory 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
80Regulatory 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
81Missing 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 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
82Dueling 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
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87Failure 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
88Failure 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
89AAALACs perspective
- Goal is avoid /minimize distress and pain in
concert with sound science - References AWA
- Does NOT reference GLPs
90AAALACs 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.
91AAALACs 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
92AAALACs perspective
- DEFFERED
-
- PROBATION
-
- INTENT TO REVOKE
- REVOKE
93Double-click on image to play
94Solution to challenge
- TEAM APPROACH TO SAFETY STUDIES
- COMMUNICATE
- Avoid GLP (us) versus AWA (them) debate
- LEARN EACH OTHERS BUSINESS
95Solution to challenge
- Pre-emptive strike critical to success
- Protocol development
- Diagnosis or treatment is permitted as long
as it does not interfere with study objective.
If the treatment interferes, the animal can be
removed - SOP development Study conduct i.e. define
nursing care -
96Solution to challenge
- Define endpoints
- Minimize mortality, opt for human euthanasia
- Rapid weight loss (15-20)
- Extended period of weight lossgtemaciation
- Prolonged lethargy
- Debilitating/prolonged diarrhea
- Condition that interferes with animals ability to
eat/drink i.e. ataxia/weakness - Bleeding, marked icterus, anemia
-
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99Research Collaborations at Land Grant
Institutions What are the Issues?
Joseph R. Haywood, Ph.D. Professor and
Chairperson Department Pharmacology
Toxicology Michigan State University
100Land 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
101Institutional philosophy
- USDA intellectual and property ownership
- AAALAC control
- PHS money
- Issues
- What are the standards of the institution?
- PHS assurance?
102Scenarios
- 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?
103Scenarios
- 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
104Scenarios
- 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
105Other known scenarios
- Spay-neuter clinic
- Veterinary clinical studies on client-owned
animals - Blood donors
- Wildlife recovery ward
106The power of communication
- Memoranda of Understanding
- Plan for Adequate Veterinary Care
- Protocol Review
- Others
- Disaster Plan
- Occupational Health concerns
- Training issues
107Practical considerations
- Think logically and talk it through
- Dont create problems
- Not every laboratory has four walls and HVAC
- What would 60 Minutes ask me?
108Names, locations, and species were changed to
protect the victims
109International 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
110What are the issues?
- Good science
- Appropriate animal care
- Regulatory compliance
- Institutional standing
- Planned oversight
111Why the concern about standards?
- Legal codes
- Regulations
- Ethical codes
- Cultures
- Language
112Due diligence
- Site visits pre/ongoing
- Written agreement
- Legal review
- IACUC review
113What needs to be clear?
- Study design
- Animal care
- Veterinary care
- Roles
- Intellectual property
114Contracts, agreements and memos of understanding
- Delineate who is responsible for what
- Regulations covering laboratory animal use
- Inspections/auditing defined
- Periodic contract, program, and inspection report
review - Notice of 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
115What can we learn from public agencies?
- Public Health Service
- The National Institutes of Health
- National Science Foundation
- Department of Defense
- National Academies of Science
- US Department of Agriculture
- Organization for Economic Cooperation and
Development
116NIH 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.
117Statement 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 acknowledges and accepts
responsibility for the care and use of animals
involved in activities covered by this Statement
of Compliance. - This Institution is guided by the International
Guiding Principles for Biomedical Research
Involving Animals developed by the Council for
International Organizations of Medical Sciences.
118International Guiding Principles for Biomedical
Research Involving Animals
- Basic Principles (XI)
- Special Provisions
- Acquisition
- Transportation
- Housing
- Environmental conditions
- Nutrition
- Veterinary care
- Records
- Monitoring
- Alternatives
119Resources
- 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
120Association For Assessment And Accreditation of
Laboratory Animal Care International
121Thank you
A sincere thanks to the following who helped with
the research for this talk
- Kathryn Bayne (AAALAC)
- Denis Doyle (NIH-OLAW)
- Betty Goldentyer (USDA)
- 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 Wolf (NIH OLAW)
- Joanne Zurlo (NAS-ILAR)
122Contact AAALAC Internationalaccredit_at_aaalac.org
www.aaalac.org301.231.5353