Transcript Contracts_Collaborations_and Co

Who Owns the Animals?
Kathryn Bayne, M.S., Ph.D., D.V.M., DACLAM
Senior Director &
Director of Pacific Rim Activities
AAALAC International
Oversight authority
 OLAW
 USDA
 AAALAC International
 Follows the money
trail
 “Covered” species on
site
 Follows animal
ownership
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….”
USDA
 The Animal Welfare Act and accompanying
Animal Welfare Regulations provide authority
(as determined by the Secretary) for warmblooded animals
 In research facilities, this includes live animals
“used or intended for use in research, testing, or
experiments”
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.
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 institution’s
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
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.
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”
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.
Defining ownership (Webster’s)
 Legal right of possession
 Lawful title to
 Proprietorship (legal title or exclusive right
to some property)
Defining Ownership
Shades of Grey
To define animal ownership:
You may need to get the lawyers
involved…
…due to possibly varying state,
municipal, and international laws
regarding property ownership specific
to your area
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
Animal Ownership
≠
Intellectual Property
Animals at your institution that you
don’t “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
Animals at your institution that you
don’t “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
Responsibility & Accountability
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
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)
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
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
Who drives the process?
 Investigator driven
 Portfolio driven
 Management driven
Each institution should develop
its own strategy, understand its
own strategy, and communicate
that strategy prior to launching
major outsourcing efforts.
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
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
Identify a legal gatekeeper
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“Trade secret” information
“Proprietary” animal models
Contracts
Animal ownership
Assurance that the CRO will comply
Reporting of adverse events
Create a list of all on-going
outsourced activities
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Centralized database
Identify approved CROs
Track ongoing outsourced activities
Identify CRO areas of expertise
Develop agreed upon criteria for CROs
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:
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Ensuring local IACUC review of animal use protocols
Ensuring that the 3 R’s 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
Evaluating CROs
 Develop evaluation criteria for:
 animal care and use program
 research program
Evaluation criteria
 Animal care and use program:
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regulatory status
IACUC activity
veterinary program
animal husbandry
Evaluation criteria
 Research program:
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technical staff capabilities
general capabilities
data collection
quality assurance programs
records and record retention system
Specifics
 Develop detailed study protocols
 Clearly state the purpose of the study
and study objectives
 Develop sample handling and transport
procedures
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!
Harmonization details
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Specific surgical details
Caging
Bedding
Water
Other considerations
 Pilot or parallel studies
 Ethical information (3Rs)
 ABSL 2 or 3
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?
Conclusions
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Don’t 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
Contracting in Research
to Universities:
What are the Issues?
Joseph N. Benoit, Ph.D.
Dean, Graduate School
University of North Dakota
Contracts are partnerships
 An agreement between two or more
parties to do or not do something
Contractee
(University)
Contractor
(Industry)
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
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.
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.
Universities are becoming
more entrepreneurial
 Research generates
 Money
 Prestige
 Intellectual property
The public’s 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 state’s economic and
demographic picture. These leaders believed the
North Dakota University System to be an integral part
of expanding and diversifying the state’s 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
What are the issues associated with
innovative university partnerships?
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Oversight
Regulatory Compliance
Infrastructure
Intellectual Property
Curiosity Driven Research vs. Contract
Driven Research
 Conflicts of Interest and Conflicts of Time
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?
Regulatory compliance
 USDA
 Which organization is held accountable for deficiencies?
 Biohazardous Agents
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Which committee reviews and approves protocol?
Pharmaceuticals with unknown properties?
Infectious agents?
Select agents?
 Radiation
 Who reviews?
 Who monitors?
 Who disposes?
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?
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?
Academic integrity issues
 Conflict of interest
 Conflict of time
Successful contracts involve
a complex balancing act
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.
Neutralizing Dual Regulations:
AWRs vs. GLPs
Kathy Laber, D.V.M., M.S., DACLAM
Professor
Medical University of South Carolina
Good Laboratory Practices
21 CFR
 Implemented in the late 70’s
 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
Nonclinical studies
Part of FDA drug approval process
 Adequate pharmacology/ toxicology drug
studies using laboratory animals or in vitro
 Supports that it’s reasonably safe to conduct
clinical investigations
Types of Studies
Single/Repeat dose toxicity, Biocompatibility,
Reproduction/Development, etc…..
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
Intended protocol focus
 GLP
 Study Conduct
 AWA
 Impact of Study on Animal Welfare
Critical Player for GLPs
Study 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
Critical player for AWA
Attending 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
Regulatory language
GLP’s
 “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…”
 “SOP’s written for : handling of animals found
moribund or dead during study”
From 21 CFR Part 58
Regulatory language
AWA
 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
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
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
Failure to address spirit of GLP’s
 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
Failure to address spirit of AWA
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Negative impact on animal
Unrelieved animal care staff pain/distress
Reportable incident to regulatory agencies
USDA citation/fine
Adverse public relationships
AAALAC’s perspective
 Goal is avoid
/minimize distress
and pain in concert
with sound science
 References AWA
 Does NOT reference
GLP’s
AAALAC’s perspective
 “..Euthanasia occurred only after receiving
permission from the study director—
contrary to principles of Guide-MUST
ensure AV has necessary authority to
ensure prompt euthanasia.”
AAALAC’s 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
AAALAC’s perspective
DEFFERED
PROBATION
INTENT TO REVOKE
REVOKE
Solution to challenge
 TEAM APPROACH TO SAFETY STUDIES
 COMMUNICATE
 Avoid GLP (us) versus AWA (them) debate
 LEARN EACH OTHER’S BUSINESS
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.
Research Collaborations
at Land Grant Institutions:
What are the Issues?
Joseph R. Haywood, Ph.D.
Professor and Chairperson
Department Pharmacology & Toxicology
Michigan State University
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
Institutional philosophy
 USDA: Intellectual and Property
Ownership
 AAALAC: Control
 PHS: Money
Issues
 What are the standards of the institution?
 PHS assurance?
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?
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
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
Other known scenarios
 Spay-neuter clinic
 Veterinary clinical studies
on client-owned animals
 Blood donors
 Wildlife recovery ward
The power of communication
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Memoranda of Understanding
Plan for Adequate Veterinary Care
Protocol Review
Others
 Disaster Plan
 Occupational Health concerns
 Training issues
Practical considerations
 Think logically and talk it through
 Don’t create problems
 Not every laboratory has four walls and
HVAC
 What would “60 Minutes” ask me?
Names, locations, and species
are changed to protect the
victims
International Research Contracts
and Collaborations Involving
Laboratory Animals
Dennis M. Stark, D.V.M., Ph.D., DACLAM
Executive Director Veterinary Sciences
Bristol-Myers Squibb
Pharmaceutical Research Institute
What are the issues?
 Good Science
 Appropriate Animal Care
 Regulatory Compliance
 Institutional Standing
 Planned Oversight
Why the concern about standards?
 Regulations
 Cultures
 Legal Codes
 Ethical Codes
 Language
Due diligence
 IACUC Review
 Legal Review
 Site Visits – Pre/Ongoing
 Written Agreement
What needs to be clear?
 Study Design
 Animal Care
 Veterinary Care
 Intellectual property
 Roles
Contracts, agreements
and memos of understanding
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Delineate who is responsible for
what
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Regulations covering laboratory
animal use
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Inspections/auditing defined/by
whom
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Review of contract, institution
program, and inspection reports
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Notice of all changes in
accreditation and regulatory
standing
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Protocol reviews
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Ownership of laboratory animals
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Animal and veterinary care
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Protect Intellectual Property
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Confidentiality provisions
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Security
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Data/Records/Samples
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
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.
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.
International Guiding Principles for
Biomedical Research Involving Animals
 Basic Principles (XI)
 Monitoring
 Special Provisions
 Alternatives
 Acquisition
 Transportation
 Housing
 Environmental Conditions
 Nutrition
 Veterinary Care
 Records
Resources
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PHS Policy on Humane Care and Use of Laboratory Animals
http://grants2.nih.gov/grants/olaw/references/PHSPolicyLab Animals.pdf
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NIH Grants Policy Statement
http://grants1.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part5.htm#_Toc54600087
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International Guiding Principles for Biomedical Research Involving Animals
http://www.cioms.ch/1985_texts_of_guidelines.htm
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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/
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International Regulations
http://www.aaalac.org/resources/internationalregs.cfm
Association For Assessment And Accreditation
of Laboratory Animal Care International
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)
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Mary Newman (BMS)
Mary Pat Nowack (NAS)
Gregory Reinhard (Merck)
James Swearengen
(AAALAC)
 Robert Trotta (BMS)
 Axel Wolff (NIH – OLAW)
 Joanne Zurlo (NAS-ILAR)
Contact AAALAC International
[email protected]
www.aaalac.org
+301.231.5353