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ANIMAL RESEARCH
IN A GLOBAL
ENVIRONMENT
MEETING THE CHALLENGES
Proceedings of the November 2008
International Workshop
Institute for Laboratory Animal Research
Division on Earth and Life Studies
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing
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tute of Medicine. The members of the committee responsible for the report were chosen
for their special competences and with regard for appropriate balance.
This workshop was supported by Contract No. N01-OD-4-2139, TO 205, between the
National Academy of Sciences and the National Institutes of Health. Any opinions, find-
ings, conclusions, or recommendations expressed in this publication are those of the au-
thor(s) and do not necessarily reflect the views of the agency that provided support for
the project.
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Printed in the United States of America
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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of
distinguished scholars engaged in scientific and engineering research, dedicated to the
furtherance of science and technology and to their use for the general welfare. Upon the
authority of the charter granted to it by the Congress in 1863, the Academy has a mandate
that requires it to advise the federal government on scientific and technical matters. Dr.
Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the
National Academy of Sciences, as a parallel organization of outstanding engineers. It is
autonomous in its administration and in the selection of its members, sharing with the
National Academy of Sciences the responsibility for advising the federal government.
The National Academy of Engineering also sponsors engineering programs aimed at
meeting national needs, encourages education and research, and recognizes the superior
achievements of engineers. Dr. Charles M. Vest is president of the National Academy of
Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences
to secure the services of eminent members of appropriate professions in the examination
of policy matters pertaining to the health of the public. The Institute acts under the re-
sponsibility given to the National Academy of Sciences by its congressional charter to be
an adviser to the federal government and, upon its own initiative, to identify issues of
medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute
of Medicine.
The National Research Council was organized by the National Academy of Sciences in
1916 to associate the broad community of science and technology with the Academy’s
purposes of furthering knowledge and advising the federal government. Functioning in
accordance with general policies determined by the Academy, the Council has become
the principal operating agency of both the National Academy of Sciences and the Na-
tional Academy of Engineering in providing services to the government, the public, and
the scientific and engineering communities. The Council is administered jointly by both
Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest
are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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STEERING COMMITTEE FOR THE INTERNATIONAL WORKSHOP
ON ANIMAL RESEARCH IN A GLOBAL ENVIRONMENT:
MEETING THE CHALLENGES
Members
Coenraad F.M. Hendriksen, Chair, Netherlands Vaccine Institute, Bilthoven,
The Netherlands
Stephen W. Barthold (IOM), Center for Comparative Medicine, University
of California, Davis
Kathryn A. Bayne, Association for Assessment and Accreditation of
Laboratory Animal Care International, Frederick, Maryland
Jeffrey Everitt, GlaxoSmithKline Research & Development, Research
Triangle Park, North Carolina
James G. Fox (IOM), Division of Comparative Medicine, Massachusetts
Institute of Technology
Joseph W. Kemnitz, Institute for Clinical and Translational Research,
University of Wisconsin, Madison
Hilton J. Klein (formerly with Merck Research Laboratories), Lansdale,
Pennsylvania
Judy A. MacArthur Clark (formerly with Pfizer), Animals Scientific
Procedures Inspectorate, Home Office, London, United Kingdom
Staff
Joanne Zurlo, Director (until April 2010)
Frances E. Sharples, Acting Director
Lida Anestidou, Senior Program Officer
Kathleen Beil, Administrative Coordinator (until April 2011)
Cameron H. Fletcher, Senior Editor
Rhonda Haycraft, Senior Project Assistant (until January 2011)
Jason Worthy, Program Assistant
v
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INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL:
2008 MEMBERSHIP
Stephen W. Barthold (IOM), Chair, Center for Comparative Medicine,
University of California, Davis
Kathryn A. Bayne, Association for Assessment and Accreditation of
Laboratory Animal Care International, Waikoloa, Hawaii
Myrtle A. Davis, Toxicology, Drug Disposition, and Pharmacokinetics,
Lilly Research Laboratories, Greenfield, Indiana
Jeffrey Everitt, Comparative Medicine and Investigator Support,
GlaxoSmithKline Research and Development, Research Triangle Park,
North Carolina
James G. Fox (IOM), Divisions of Comparative Medicine and of Biological
Engineering, Massachusetts Institute of Technology, Cambridge
Nelson L. Garnett, Consultant, Laboratory Animal Care and Use Programs,
Dickerson, Maryland
Estelle B. Gauda, Division of Neonatology, Johns Hopkins University School
of Medicine, Baltimore, Maryland
Joseph W. Kemnitz, National Primate Research Center, University of
Wisconsin, Madison
Judy A. MacArthur Clark, Animals Scientific Procedures Inspectorate,
London, United Kingdom
Martha K. McClintock (IOM), Institute for Mind and Biology, The
University of Chicago
Leticia V. Medina, Animal Welfare and Compliance, Abbott Laboratories,
Abbott Park, Illinois
Timo Olavi Nevalainen, National Laboratory Animal Center, University of
Kuopio, Finland
Bernard E. Rollin, Department of Animal Sciences, Colorado State
University, Fort Collins
Abigail Smith, School of Veterinary Medicine, University of Pennsylvania,
Philadelphia
Stephen A. Smith, Department of Biomedical Sciences and Pathobiology,
VA-MD Regional College of Veterinary Medicine, Virginia
Polytechnic Institute and State University, Blacksburg
James E. Womack, Department of Veterinary Pathobiology, Texas A&M
University, College Station
vi
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INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL:
2011 MEMBERSHIP
Members
Floyd E. Bloom (IOM), Chair, Molecular and Integrative Neuroscience
Department (emeritus), Scripps Research Institute, La Jolla, California
Kathryn A. Bayne, Association for Assessment and Accreditation of
Laboratory Animal Care International, Frederick, Maryland
Myrtle A. Davis, Division of Cancer Treatment and Diagnosis, National
Cancer Institute, National Institutes of Health, Bethesda, Maryland
Nelson L. Garnett, Consultant, Laboratory Animal Care and Use Programs,
Dickerson, Maryland
Judy A. MacArthur Clark, Animals Scientific Procedures Inspectorate,
London, United Kingdom
Daniel S. Marsman, Personal Health/Feminine Care Safety, Procter &
Gamble, Mason, Ohio
Garry Neil, Corporate Office of Science and Technology, Johnson & Johnson,
New Brunswick, New Jersey
Timo O. Nevalainen, Professor Emeritus, University of Eastern Finland,
Kuopio
Steven M. Niemi, Center for Comparative Medicine, Massachusetts General
Hospital, Charlestown
Melinda A. Novak, Department of Psychology, University of Massachusetts,
Amherst
Menelas Pangalos, Innovative Medicine Units, AstraZeneca, Alderley Park,
United Kingdom
Bernard E. Rollin, Departments of Philosophy, Behavorial Sciences, and
Animal Sciences, Colorado State University, Fort Collins
James A. Roth, Center for Food Security and Public Health, College of
Veterinary Medicine, Iowa State University, Ames
Staff
Frances E. Sharples, Acting Director
Lida Anestidou, Senior Program Officer
Cameron H. Fletcher, Managing Editor, ILAR Journal
Jason Worthy, Program Assistant
vii
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Preface
THE GLOBALIZATION OF ANIMAL RESEARCH:
SCIENCE AND ETHICS AS A FOUNDATION FOR STANDARDS
Impacts of Globalization
International economist Jagdish Bhagwati has called globalization the
“most powerful force for social good in the world today” (Bhagwati 2004, ix).
Yet, in the wake of highly publicized news stories about counterfeit pharmaceu-
ticals, the 2007 pet food recall, and tainted heparin supplies, other voices loudly
criticize the loss of jobs in America and of quality assurance for products asso-
ciated with international outsourcing.
In addition, pressures on both the health care industry—which relies heav-
ily on animal models for biomedical research and preclinical trials—and science
in general continue to build. A variety of sources provide data showing that de-
mands for new and better medications and for research on health and quality of
life will grow, in large part due to the expanding global population.
In 2006 the United Nations noted that in just 12 years the world popu-
lation was expected to climb from 6.7 billion to 7.6 billion (UN 2006b).
The American Veterinary Medical Association has described the health
risks to this increasing population: “The convergence of people, animals, and
our environment has created a new dynamic in which the health of each group is
inextricably interconnected. The challenges associated with this dynamic are
demanding, profound, and unprecedented” (AVMA 2008, 3).
The World Health Report states that “the global health economy is
growing faster than gross domestic product (GDP)…. In absolute terms, ad-
justed for inflation, this represents a 35% growth in the world’s expenditure on
health over a five-year period” (WHO 2008, xii).
And three of the UN Millennium Development Goals (www.un.org/
millenniumgoals) specifically address health: child health (Goal 4), maternal
health (Goal 5), and the prevention and treatment of HIV/AIDS, malaria, and
other diseases (Goal 6).
ix
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x Preface
Animal research will play an essential role in efforts to meet these increas-
ing demands for global health care. Yet the animal research community faces
the challenge of overcoming negative impressions that industry and academia
engage in international collaborations in order to conduct work in parts of the
world where animal welfare standards are less stringent. Thus the importance of
ensuring the international harmonization of the principles and standards of ani-
mal care and use cannot be overstated. A number of national and international
groups are actively working toward this goal.
The Role of the Institute for Laboratory Animal Research
The Institute for Laboratory Animal Research (ILAR), a program unit of
the US National Research Council, is committed to promoting both the welfare
of animals used in research and the quality of the resulting science. To that end,
it convenes those involved in such research and related activities—investigators,
attending veterinarians and animal care technicians, policymakers and oversight
committee members, and educators, from academia, industry, professional so-
cieties, and government—to participate in workshops that address both broad
and particular challenges in the increasing globalization of animal research.
In 2003 ILAR hosted an international workshop to examine the Develop-
ment of Science-Based Guidelines for Laboratory Animal Care (NRC 2004).
Participants discussed the available knowledge that could positively influence a
framework of standards of laboratory animal care and identified gaps in critical
information. A common thread in the discussions was the subject of harmoniza-
tion of animal care standards, specifically its merits and challenges. While scien-
tific evidence was certainly identified as critical to decisions regarding animal
care, participants also recognized cultural context as an intrinsic factor in such
decisions. Many speakers and participants observed that, despite much progress
in the establishment of standards for the objective evaluation of animal care and
housing practices, a great deal of work remained to be done.
In 2007 ILAR convened an international meeting of laboratory animal
medicine specialists to review the regulatory and guidance documents of several
countries; the group analyzed descriptions in these documents of the role of the
veterinarian in this type of work and also determined whether training in areas
specific to laboratory animal species is required or recommended. This review
(Zurlo et al. 2009) revealed both commonalities (e.g., in the provision of clinical
care) and significant differences (e.g., in the designation of who at the institution
has decision-making authority regarding euthanasia).
In 2008, to follow up on the 2003 event, ILAR convened a workshop to
define more precisely the types of information still needed and to identify the
data necessary to enable prioritization of research and funding support for re-
lated initiatives. This workshop, on Animal Research in a Global Environment:
Meeting the Challenges, brought together 200 participants from 17 countries
with a diversity of perspectives. The speakers and participants noted that the
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Preface xi
landscape of animal-based research had changed in some significant ways since
the 2003 workshop. Globalization of biomedical research was well under way.
Outsourcing of research, sometimes to countries with widely divergent regula-
tory systems of oversight, had become an important element of the biomedical
research enterprise, and academic collaborations across country borders were
commonplace. Yet air transportation of animals was becoming more restricted.
And there was increasing public concern about the quality of products and ser-
vices from certain regions of the world. Calls for improvement in laboratory
animal welfare and data quality became more prominent and the need for glob-
ally accepted approaches to the responsible and ethical conduct of animal re-
search more pressing.
Organization and Content of the Workshop
Fully cognizant of the demands and cautions related to the globalization of
animal research, ILAR appointed a Workshop Steering Committee, composed of
US and foreign individuals from academia, industry, and the nonprofit sector, to
design the program for the 2008 workshop such that session speakers might
identify and promote better understanding of important challenges in the con-
duct of animal research across country boundaries. These challenges appear in
the sourcing of animals; the quality of veterinary care; appropriately qualified
and competent staff; the provision of a suitable environment (including nutri-
tious food and potable water) for animals, both during transport and at the insti-
tution; ethical review of the proposed work and ongoing oversight of the animal
program; suitable facilities and equipment in which to conduct the work; appro-
priate policies and procedures; and protection of the personnel involved in the
animal program.
General topics that framed the first day of discussions were challenges and
opportunities for harmonization, with representatives from seven organizations
providing a variety of international perspectives; operational challenges of
working across differing global standards, with representatives from the phar-
maceutical industry, contract research organizations (CROs), and academia de-
scribing their experiences; and the training and educational challenges of work-
ing across different global standards, with colleagues from various regions of the
world illustrating how training programs can overcome those challenges.
On the second day speakers examined in more detail specific issues that
require attention. They discussed the varying standards and state of veterinary
care for research animals around the world as well as potential steps toward
harmonizing veterinary education in laboratory animal medicine and standards
for laboratory animal care. Presenters also described international principles and
approaches to pain, distress, euthanasia, and humane endpoints.
The third day opened with a session concerning efforts to coordinate in-
ternational rodent resources, for example by facilitating transportation, enhanc-
ing databases, and addressing repository issues. The afternoon presentations
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xii Preface
were devoted to nonhuman primate resources, reviewing the scope of the need
for primates in research, the concept of an International Primate Plan to investi-
gate and report on supply and demand, the need for harmonized care standards,
and transportation concerns.
Impacts of the Workshop
The impact of this 2008 workshop has extended beyond the oral presenta-
tions conveyed in these proceedings. It has been a vital bridge for diverse col-
leagues and organizations around the world to advance initiatives designed to
fill gaps in standards, professional qualifications, and coordination of animal
use.
The World Organization for Animal Health (the OIE), with the involve-
ment of speakers from the 2008 ILAR workshop, has published standards on the
use of animals in research as part of its Terrestrial Animal Code, which includes
a specific chapter regarding the care and use of research animals. Thanks to the
OIE’s status as a reference organization for the World Trade Organization
(WTO), the Code serves as a standards template for the 178 member countries
and territories of the OIE and thus applies to numerous economies and cultures.
In addition, ILAR, the OIE, and the International Association of Colleges
of Laboratory Animal Medicine (IACLAM) convened focus groups to assess the
laboratory animal veterinary community’s perspective on harmonizing global
veterinary qualifications and training in laboratory animal medicine. These
groups met in 2010 at three pivotal laboratory animal science meetings held in
Europe, the United States, and Asia: the June meeting of the Federation of Labo-
ratory Animal Science Associations (FELASA) in Helsinki; the September
meeting of the Association for Laboratory Animal Science (AALAS) in Atlanta;
and the November meeting of the Asian Federation of Laboratory Animal Sci-
ence (AFLAS) Associations in Taipei. More than 100 individuals representing
27 countries participated in the three meetings, the results of which will be pub-
lished in the online ILAR Journal.
Finally, development of an International Primate Plan (IPP) continues to
gain momentum. In 2009 ILAR hosted an international meeting in Irvine, Cali-
fornia, to determine the outline and approach to the plan. The participants repre-
sented key stakeholders such as researchers, veterinarians, and suppliers. Fo-
cused meetings were held in association with the 2010 AFLAS congress, and the
IPP has been discussed with the National Institutes of Health (NIH), EUPRIM-
NET (the European Primate Network), and the Interagency Research Advisory
Committee (IRAC) of the US federal government. Substantial progress has been
made toward the launch of the plan.
The papers in these proceedings describe important topics facing the bio-
medical research enterprise. Time has not stood still since the workshop and
there has been progress in some areas, yet much work remains to be done—
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Preface xiii
requiring additional attention and resources—to address many of the issues de-
scribed in the following papers.
A Note about the Transcripts
The transcripts in these proceedings are those approved by the speakers;
presentations shown on the agenda but without a corresponding transcript are
those for which the speaker did not provide permission for publication. The
transcripts have been only lightly edited, largely for clarity, the addition of
sources, and, when appropriate and possible, updating to incorporate the out-
come of reports issued or events held since 2008. The report and speakers’ slides
are posted on the ILAR website.
Acknowledgments
ILAR thanks the US National Institutes of Health, which sponsored this
workshop, and the members of the Workshop Steering Committee.
Kathryn A. Bayne
Global Director, AAALAC International
References
AVMA [American Veterinary Medical Association]. 2008. One Health: A New Profes-
sional Initiative. Available online (www.avma.org/onehealth/onehealth_final.pdf),
accessed on April 14, 2011.
Bhagwati J. 2004. In Defense of Globalization. New York: Oxford University Press.
NRC [National Research Council]. 2004. Development of Science-Based Guidelines for
Laboratory Animal Care: Proceedings of the November 2003 International Work-
shop. Washington: National Academies Press.
OIE [World Organization for Animal Health]. 2010. Use of Animals in Research: Terres-
trial Animal Health Code. Available online (www.oie.int/index.php?id=169&L=
0&htmfile=chapitre_1.7.8.htm), accessed on April 14, 2011.
UN [United Nations]. 2006a. The Millennium Development Goals Report 2006. Avail-
able online (http://mdgs.un.org/unsd/mdg/Resources/Static/Products/Progress2006/
MDGReport2006.pdf), accessed on April 14, 2011.
UN. 2006b. World Population Prospects: The 2006 Revision. Available online (www.
un.org/esa/population/publications/wpp2006/WPP2006_Highlights_rev.pdf), accessed
on April 14, 2011.
WHO [World Health Organization]. 2008. The World Health Report 2008: Primary
Health Care Now More Than Ever. Available online (www.who.int/whr/2008/
whr08_en.pdf), accessed on April 14, 2011.
Zurlo J, Bayne K, MacArthur Clark J. 2009. Adequate veterinary care for animals in
research: A comparison of guidelines from around the world. ILAR J 50:85-88.
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CONTENTS
PLENARY LECTURE ................................................................................................ 1
Science & Technology and US Foreign Policy, 3
Norman Neureiter
INTRODUCTORY LECTURE .............................................................................. 13
Building Momentum: Lessons Learned from
the 2003 ILAR International Conference, 15
Hilton Klein
CHALLENGES AND OPPORTUNITIES FOR HARMONIZATION
Perspectives from International Organizations .......................................... 23
International Council for Laboratory Animal Science (ICLAS), 25
Cecilia Carbone
World Organization for Animal Health (OIE), 27
David Bayvel
Adequate Veterinary Care and the International Association of
Colleges of Laboratory Animal Medicine (IACLAM), 29
Judy MacArthur Clark
Association for Assessment and Accreditation of Laboratory
Animal Care (AAALAC) International, 32
Kathryn Bayne
International Air Transport Association (IATA), 34
Carl Kole
Institute for Laboratory Animal Research (ILAR), 36
Joanne Zurlo
The European Union, 38
Malachy Hargadon
xv
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xvi
Contents
Global Issues: Working Across Different Standards ................................. 41
Operational Challenges—Pharmaceutical Industry, 41
Margaret Landi
Overcoming Challenges—Contract Research Organizations (CROs):
Setting Up a CRO in a Foreign Country, 46
Bryan Ogden
Global Issues: Operational Challenges to Working across Different
Standards in Academia, 54
Steven M. Niemi
Overcoming Challenges—Academia in Europe, 62
Harry van Steeg
Training and Education .................................................................................... 67
Charles River: A Model of International Training, 67
Marilyn Brown
The FELASA Training Program, 73
Patri Vergara
PLENARY LECTURE .............................................................................................. 79
Animal Research in a Global Environment: Meeting the Challenges, 81
John Baldoni
VETERINARY CARE FOR LABORATORY ANIMALS .............................. 93
Standards of Veterinary Care for Laboratory Animals, 95
Kathryn Bayne
State of Laboratory Animal Medicine Around the World ..................... 102
Europe, 102
Hans Hedrich
Latin America, 106
Rafael Hernandez
North America, 109
James G. Fox
A Path Forward ................................................................................................. 113
Role of the OIE, 113
David Bayvel
Introduction to AAVMC, 117
Marguerite Pappaioanou
AAVMC Strategic Plan, 119
Michael Chaddock
Online Training and Distance Learning, 122
Patricia V. Turner
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xvii Contents
International Approaches and Principles for
Distress, Pain, and Euthanasia ...................................................................... 128
Distress, 128
David Morton
Pain: International Differences Across Guidelines
and Approaches, 135
Matt Leach
Euthanasia, 141
Gilly Griffin
International Approaches and Principles for
Humane Endpoints ........................................................................................... 153
Humane Endpoints in Cancer Research, 153
Fraser Darling
Humane Endpoints in Infectious Disease, 156
Carol Eisenhauer
Humane Endpoints and Genetically Modified Animal Models:
Opportunities and Challenges, 160
Margaret Rose
Cross-Cultural Ethical Perceptions and Ways to
Resolve Challenges, 173
Bernard Rollin
COORDINATION OF INTERNATIONAL
RODENT RESOURCES ......................................................................................... 185
Mice Traveling the World: Issues in Sharing and
Transferring Mice, 187
Lili M. Portilla
Knockout Mouse Databases: The Knockout Mouse
Project and Repository, 191
Franziska Grieder
NorCOMM, the North American Conditional Mouse
Mutagenesis Project, 194
Colin McKerlie
EUCOMM, the European Conditional Mouse
Mutagenesis Program, 199
Martin Hrabé de Angelis
The RIKEN BioResource Center, 202
Yuichi Obata
Repository Issues—Lessons Learned, 205
James Womack
Transportation and the “Mouse Passport,” 209
William White
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xviii
Contents
INTERNATIONAL COORDINATION OF
NONHUMAN PRIMATES .................................................................................... 215
Framing the Issues, 217
Joseph Kemnitz
Supply and Use of NHP Around the World ............................................... 219
The United States, 219
William Morton
China as a Resource for NHP, 224
C.K. Hsu
New World Primates in Research, 228
Chris Abee
Challenges in Outsourcing Studies ............................................................... 232
An Academic Perspective, 232
James Macy
Perspective from China, 236
Alex Zhang
Transportation Issues with Nonhuman Primates, 239
Saverio Capuano
The Future of the Use of Nonhuman Primates in the UK, 241
Judy MacArthur Clark
Proposed International NHP Plan, 246
Joseph Kemnitz
ABBREVIATIONS................................................................................................... 249
APPENDIX A: WORKSHOP AGENDA ........................................................... 252
APPENDIX B: STEERING COMMITTEE BIOS........................................... 258
APPENDIX C: WORKSHOP SPEAKERS ....................................................... 261
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ANIMAL RESEARCH
IN A GLOBAL
ENVIRONMENT
MEETING THE CHALLENGES
Proceedings of the November 2008
International Workshop
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