Guide for the Care and Use of Laboratory Animals, 8th edition

GUIDE

LABORATORY

ANIMALS

FOR THE CARE AND USE OF

Eighth Edition

Committee for the Update of the Guide for the Care

and Use of Laboratory Animals

Institute for Laboratory Animal Research

Division on Earth and Life Studies

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 Govern-

ing Board of the National Research Council, whose members are drawn from the

councils of the National Academy of Sciences, the National Academy of Engineer-

ing, and the Institute of Medicine. The members of the Committee responsible for

the report were chosen for their special competences and with regard for appropriate

balance.

This study was supported by the Ofﬁce of Extramural Research, Ofﬁce of the Direc-

tor, National Institutes of Health/Department of Health and Human Services under

Contract Number N01-OD-4-2139 Task Order #188; the Ofﬁce of Research Integrity,

Department of Health and Human Services; the Animal and Plant Health Inspection

Service, U.S. Department of Agriculture; Association for Assessment and Accreditation

of Laboratory Animal Care International; American Association for Laboratory Animal

Science; Abbott Fund; Pﬁzer; American College of Laboratory Animal Medicine; Ameri-

can Society of Laboratory Animal Practitioners; Association of Primate Veternarians.

Any opinions, ﬁndings, conclusions, or recommendations expressed in this pub-

lication are those of the authors and do not necessarily reﬂect the views of the

organizations or agencies that provided support for the project. The content of

this publication does not necessarily reﬂect the views or policies of the National

Institutes of Health, nor does mention of trade names, commercial products, or

organizations imply endorsement by the US government.

International Standard Book Number-13: 978-0-309-15400-0 (Book)

International Standard Book Number-10: 0-309-15400-6 (Book)

International Standard Book Number-13: 978-0-309-15401-7 (PDF)

International Standard Book Number-10: 0-309-15401-4 (PDF)

Library of Congress Control Number: 2010940400

Additional copies of this report are available from the National Academies Press,

500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or

(202) 334-3313 (in the Washington metropolitan area); http://www.nap.edu.

Printed in the United States of America.

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 Acad-

emy 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 engineer-

ing programs aimed at meeting national needs, encourages education and research,

and recognizes the superior achievements of engineers. Dr. Charles 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 Insti-

tute acts under the responsibility 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 Sci-

ences 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 National 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

COMMITTEE FOR THE UPDATE OF THE GUIDE FOR THE CARE

AND USE OF LABORATORY ANIMALS

Members

Janet C. Garber (Chair), Garber Consulting

R. Wayne Barbee, Virginia Commonwealth University

Joseph T. Bielitzki, University of Central Florida

Leigh Ann Clayton, National Aquarium, Baltimore

John C. Donovan, BioResources, Inc.

Coenraad F. M. Hendriksen, Netherlands Vaccine Institute, Bilthoven,

The Netherlands (until March 2009)

Dennis F. Kohn, Columbia University (retired)

Neil S. Lipman, Memorial Sloan-Kettering Cancer Center and WeillWeill

Cornell Medical College

Paul A. Locke, Johns Hopkins Bloomberg School of Public Health

John Melcher, U.S. Senate (retired)

Fred W. Quimby, Rockefeller University (retired)

Patricia V. Turner, University of Guelph, Canada

Geoffrey A. Wood, University of Guelph, CanadaUniversity of Guelph, Canada

Hanno Würbel, Justus Liebig University of Giessen, Germany

Staff

Lida Anestidou, Study Director

Frances Sharples, Acting Director

Kathleen Beil, Administrative Coordinator Administrative CoordinatorAdministrative Coordinator

Cameron H. Fletcher, Senior Editor

Ruth Crossgrove, Senior Editor

Radiah Rose, Manager of Editorial Projects

Rhonda Haycraft, Senior Project Assistant Senior Project AssistantSenior Project Assistant

Joanne Zurlo, Director (until April 2010)

INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL

Members

Stephen W. Barthold (Chair), Center for Comparative Medicine,

University of California-Davis

Kathryn A. Bayne, Association for Assessment and Accreditation of

Laboratory Animal Care International, Frederick, Maryland

Myrtle A. Davis, National Cancer Institute, National Institutes of Health,

Bethesda, Maryland

Jeffrey I. Everitt, Comparative Medicine and Investigator Support,

GlaxoSmithKline Research and Development, Research Triangle Park,

North Carolina (until June 2010)

James G. Fox, Division of Comparative Medicine, Massachusetts Institute

of Technology, Cambridge

Nelson L. Garnett, Laboratory Animal Care and Use Programs,

Dickerson, MD

Estelle B. Gauda, Johns Hopkins University School of Medicine, Johns

Hopkins Hospital, Baltimore, Maryland (until June 2010)

Joseph W. Kemnitz, Institute for Clinical and Translational Research and

Department of Physiology, University of Wisconsin-Madison

Judy A. MacArthur Clark, Animals in Scientiﬁc Procedures Inspectorate,

Home Ofﬁce, London, United Kingdom

Martha K. McClintock, Institute for Mind and Biology, University of

Chicago, Illinois

Leticia V. Medina, Animal Welfare and Compliance, Abbott Laboratories,

Abbott Park, Illinois

Timo Olavi Nevalainen, National Laboratory Animal Center, University of

Eastern Finland, Kuopio, Finland

Bernard E. Rollin, Department of Animal Sciences, Colorado State

University, Fort Collins

Abigail L. Smith, School of Veterinary Medicine, University of

Pennsylvania, Philadelphia (until June 2010)

Stephen A. Smith, Department of Biomedical Sciences and Pathobiology,

Virginia Polytechnic Institute and State University, Blacksburg

James E. Womack, Department of Veterinary Pathology, Texas A&M

University, College Station (until June 2010)

vii

Staff

Frances Sharples, Acting Director

Lida Anestidou, Senior Program Ofﬁcer

Kathleen Beil, Administrative Coordinator Administrative CoordinatorAdministrative Coordinator

Cameron H. Fletcher, Managing Editor, ILAR Journal

Rhonda Haycraft, Program Associate Program AssociateProgram Associate

Joanne Zurlo, Director (until April 2010)

viii

INSTITUTE FOR LABORATORY ANIMAL RESEARCH PUBLICATIONS

Recognition and Alleviation of Pain in Laboratory Animals (2009)

Scientiﬁc and Humane Issues in the Use of Random Source Dogs and

Cats for Research (2009)

Recognition and Alleviation of Distress in Laboratory Animals (2008)

Toxicity Testing in the 21st Century: A Vision and a Strategy (2007)

Overcoming Challenges to Develop Countermeasures Against Aerosolized

Bioterrorism Agents: Appropriate Use of Animal Models (2006)

Guidelines for the Humane Transportation of Research Animals (2006)

Science, Medicine, and Animals: Teacher’s Guide (2005)

Animal Care and Management at the National Zoo: Final Report (2005)

Science, Medicine, and Animals (2004)

The Development of Science-based Guidelines for Laboratory Animal

Care: Proceedings of the November 2003 International Workshop

(2004)

Animal Care and Management at the National Zoo: Interim Report (2004)

National Need and Priorities for Veterinarians in Biomedical Research

(2004)

Guidelines for the Care and Use of Mammals in Neuroscience and

Behavioral Research (2003)

International Perspectives: The Future of Nonhuman Primate Resources,

Proceedings of the Workshop Held April 17-19, 2002 (2003)

Occupational Health and Safety in the Care and Use of Nonhuman

Primates (2003)

Deﬁnition of Pain and Distress and Reporting Requirements for Laboratory

Animals: Proceedings of the Workshop Held June 22, 2000 (2000)

Strategies That Inﬂuence Cost Containment in Animal Research Facilities

(2000)

Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of

the 1999 US/Japan Conference (2000)

Microbial and Phenotypic Deﬁnition of Rats and Mice: Proceedings of the

1998 US/Japan Conference (1999)

Monoclonal Antibody Production (1999)

The Psychological Well-Being of Nonhuman Primates (1998)

Biomedical Models and Resources: Current Needs and Future

Opportunities (1998)

Approaches to Cost Recovery for Animal Research: Implications for

Science, Animals, Research Competitiveness and Regulatory

Compliance (1998)

Chimpanzees in Research: Strategies for Their Ethical Care, Management,

and Use (1997)

Occupational Health and Safety in the Care and Use of Research Animals

(1997)

Guide for the Care and Use of Laboratory Animals (1996)

Rodents (1996)

Nutrient Requirements of Laboratory Animals, Fourth Revised Edition

(1995)

Laboratory Animal Management: Dogs (1994)

Recognition and Alleviation of Pain and Distress in Laboratory Animals

(1992)

Education and Training in the Care and Use of Laboratory Animals: A

Guide for Developing Institutional Programs (1991)

Companion Guide to Infectious Diseases of Mice and Rats (1991)

Infectious Diseases of Mice and Rats (1991)

Immunodeﬁcient Rodents: A Guide to Their Immunobiology, Husbandry,

and Use (1989)

Use of Laboratory Animals in Biomedical and Behavioral Research (1988)

Animals for Research: A Directory of Sources, Tenth Edition and

Supplement (1979)

Amphibians: Guidelines for the Breeding, Care and Management of

Laboratory Animals (1974)

Copies of these reports may be ordered from the National Academies Press

(800) 624-6242 or (202) 334-3313

www.nap.edu

Reviewers

his eighth edition of the Guide for the Care and Use of Laboratory

Animals has been reviewed in draft form by individuals chosen for

their diverse perspectives and expertise, in accordance with proce-

dures approved by the Report Review Committee of the National Research

Council. The purpose of this independent review is to provide candid and

critical comments that will assist the Committee in making its published

report as sound as possible, and to ensure that the report meets institutional

standards for objectivity, evidence, and responsiveness to the study charge.

The review comments and draft manuscript remain conﬁdential to protect

the integrity of the deliberation process. The Committee thanks the follow-

ing individuals for their review of the draft report:

Michael B. Ballinger, Amgen

Philippe J.R. Baneux, PreLabs

Stephen W. Barthold, University of California-Davis

Linda C. Cork, Stanford University

Jann Hau, University of Copenhagen, Denmark

Michael J. Huerkamp, Emory University

Michael D. Kastello, sanoﬁ-aventis

Arthur L. Lage, Harvard Medical School

Christian Lawrence, Children’s Hospital Boston

Randall J. Nelson, University of Tennessee College of Medicine-

Memphis

Steven M. Niemi, Massachusetts General Hospital

Melinda A. Novak, University of Massachusetts-Amherst

xii REVIEWERS

Gemma Perretta, National Research Council, Italy

Marky E. Pitts, IACUC Consultant

George E. Sanders, University of Washington

Allen W. Singer, Battelle Memorial Institute

William J. White, Charles River Laboratories

Although the reviewers listed above have provided many constructive

comments and suggestions, they were not asked to endorse the conclusions

or recommendations nor did they see the ﬁnal draft of the report before

its release. The review of this report was overseen by John Dowling, Har-

vard University, and John Vandenbergh, North Carolina State University.

Appointed by the National Research Council, they were responsible for

making certain that an independent examination of this report was carried

out in accordance with institutional procedures and that all review com-

ments were carefully considered. Responsibility for the ﬁnal content of this

report rests entirely with the authoring committee and the institution.

xiii

Preface

he purpose of the Guide for the Care and Use of Laboratory Animals

(the Guide), as expressed in the charge to the Committee for the

Update of the Guide, is to assist institutions in caring for and using

animals in ways judged to be scientiﬁcally, technically, and humanely

appropriate. The Guide is also intended to assist investigators in fulﬁlling

their obligation to plan and conduct animal experiments in accord with the

highest scientiﬁc, humane, and ethical principles. Recommendations in the

Guide are based on published data, scientiﬁc principles, expert opinion,

and experience with methods and practices that have proved to be con-

sistent with both high-quality research and humane animal care and use.

These recommendations should be used as a foundation for the develop-

ment of a comprehensive animal care and use program, recognizing that

the concept and application of performance standards, in accordance with

goals, outcomes, and considerations deﬁned in the Guide, is essential to

this process.

The Guide is an internationally accepted primary reference on animal

care and use, and its use is required in the United States by the Public

Health Service Policy. It was ﬁrst published in 1963, under the title Guide

for Laboratory Animal Facilities and Care, and was revised in 1965, 1968,

1972, 1978, 1985, and 1996. More than 550,000 copies have been printed

since its ﬁrst publication.

In 2006 an ad hoc committee appointed by the Institute for Laboratory

Animal Research recommended that the Guide be updated. The Committee

for the Update of the Guide for the Care and Use of Laboratory Animals

was appointed in 2008 by the National Research Council; its 13 members

xiv PREFACE

included research scientists, veterinarians, and nonscientists representing

biomedical ethics and the public’s interest in animal welfare. The Commit-

tee widely solicited written and oral comments on the update of the Guide

from the scientiﬁc community and the general public; comments at open

meetings (on September 26, 2008, in Washington, DC; October 16, 2008,

in Irvine, California; and November 14, 2008, in Chicago) as well as written

comments submitted to or requested by the Committee were considered. In

addition, the Committee studied the materials submitted to NIH in response

to its 2005 Request for Information (NOT-OD-06-011). All comments con-

tributed substantially to this eighth edition of the Guide.

In approaching its task, the Committee carried forward the balance

between ethical and science-based practice that has always been the basis

of the Guide, and fulﬁlled its role to provide an updated resource that

enables the research community to proceed responsibly and in a self-regula-

tory manner with animal experimentation. The Guide is predicated on the

understanding that the exercise of professional judgment both upholds the

central notion of performance standards and obviates the need for more

stringent regulations.

Laboratory animal science is a rapidly evolving ﬁeld and the Com-

mittee identiﬁed a number of areas in which current available scientiﬁc

information is insufﬁcient; additional objective information and assessment

are needed to provide a scientiﬁc basis for recommendations in future

editions of the Guide. Although pursuing these concepts was beyond this

Committee’s charge, the following two topics merit further study: (1) space

and housing needs of laboratory species and (2) the need and best methods

for providing enrichment, exercise, and human contact.

The need for continual updating of the Guide is implicit in its objective

“to provide information that will enhance animal well-being, the quality of

research, and the advancement of scientiﬁc knowledge that is relevant to

both humans and animals” (Chapter 1). The irregular and increasing inter-

vals between updates, reaching a 14-year gap between the seventh edition

and this eighth edition, mean that important new research ﬁndings might

wait more than a decade before being reﬂected in recommended practice.

Addressing this concern was beyond the charge of this Committee; we

noted, however, that regular and more frequent updates of the information

in the Guide will promote laboratory animal welfare and support high-qual-

ity scientiﬁc data. A formal process for revising the information in the Guide,

including the updating of practice standards, could meet this need.

In undertaking this update, the Committee acknowledged the contribu-

tions of William I. Gay and Bennett J. Cohen in the development of the orig-

inal Guide. In 1959, Animal Care Panel (ACP) President Cohen appointed

the Committee on Ethical Considerations in the Care of Laboratory Animals

to evaluate animal care and use. That Committee was chaired by Dr. Gay,

PREFACE xv

who soon recognized that the Committee could not evaluate animal care

programs objectively without appropriate criteria on which to base its

evaluations—that is, standards were needed. The ACP Executive Commit-

tee agreed, and the Professional Standards Committee was appointed. NIH

later awarded the ACP a contract to “determine and establish a professional

standard for laboratory animal care and facilities.” Dr. Cohen chaired the

ACP Animal Facilities Standards Committee, which prepared the ﬁrst Guide

for Laboratory Animal Facilities and Care.

This edition of the Guide was ﬁnancially supported by the National

Institutes of Health; the Ofﬁce of Research Integrity, Department of Health

and Human Services; the US Department of Agriculture (USDA); the Asso-

ciation for Assessment and Accreditation of Laboratory Animal Care Inter-

national; the American Association for Laboratory Animal Science; Abbott

Fund; Pﬁzer, Inc.; the American College of Laboratory Animal Medicine; the

American Society of Laboratory Animal Practitioners; and the Association

of Primate Veterinarians.

The Committee for the Update of the Guide for the Care and Use of

Laboratory Animals expresses its appreciation to the Animal Welfare Infor-

mation Center, National Agricultural Library, USDA, for its assistance in

compiling bibliographies and references. This task would have been formi-

dable without the help of the Center’s staff. Appreciation is also extended to

the reviewers of this volume, to Rhonda Haycraft for providing exemplary

administrative and logistical assistance, and especially to Lida Anestidou,

Study Director, who, through extraordinary patience, persistence, and sci-

entiﬁc insight, managed the process from beginning to end.

Readers who detect errors of omission or commission are invited to

send corrections and suggestions to the Institute for Laboratory Animal

Research, National Research Council, 500 Fifth Street NW, Washington,

DC 20001.

Janet C. Garber, Chair

Committee for the Update of the Guide for the

Care and Use of Laboratory Animals

xvii

Overview

his eighth edition of the Guide is divided into ﬁve chapters and four

appendices.

Chapter 1 presents the goals and intended audiences of the

Guide as well as key concepts and terminology essential to its premise

and use. Incorporating some of the material from the Introduction to the

last edition, the chapter highlights a commitment to the concepts of the

Three Rs—Replacement, Reduction, and Reﬁnement—and provides an

enhanced discussion of the ethics of animal use and investigator/institu-

tional obligations.

Chapter 2 focuses on the overall institutional animal care and use

program (Program), in addition to many of the topics previously covered in

Chapter 1 of the seventh edition. It deﬁnes the evolved concept of Program

and provides a framework for its intra-institutional integration, taking into

account institutional policies and responsibilities, regulatory considerations,

Program and personnel management (including training and occupational

health and safety), and Program oversight. Discussions of the latter include

institutional animal care and use committee (IACUC) functions, protocol

and Program review, postapproval monitoring (a new section), and consid-

erations such as humane endpoints and multiple survival surgical proce-

dures. The Committee endorses the American College of Laboratory Animal

Medicine’s “Guidelines for Adequate Veterinary Care.”

Chapter 3 focuses on the animals themselves and, unlike previous edi-

tions, addresses terrestrial and aquatic species in separate sections, reﬂect-

xviii OVERVIEW

ing the growing role of aquatic animals in biomedical research. The chapter

provides recommendations for housing and environment, discusses the

importance of social housing, and includes enhanced sections on environ-

mental enrichment, animal well-being, and scientiﬁc validity.

Space recommendations were nominally expanded based on the Com-

mittee’s professional and expert opinion and on current housing methods.

Cage sizes have historically been interpreted as minimum space needs by

users of the Guide, and were labeled as such (“recommended minimum

space”) in this edition. The use of the word “minimum” does not further

restrict users of the Guide because, although the space requirements are

numbers (i.e., engineering standards), they are used in a performance stan-

dards framework. The Committee recommends minimum space for female

rodents with litter and an increase of the cage height for rabbits to 16”.

Further, in light of many comments submitted to the Committee requesting

more information on performance goals and how to achieve them, rodent

breeding recommendations are accompanied by substantial guidance.

With respect to nonhuman primates (NHPs), the Committee endorses

social housing as the default and has provided some species-speciﬁc guid-

ance. An additional group has been added for monkeys, and chimpanzees

are separated in a new category. These changes were motivated by the

Committee’s recognition (afﬁrmed in comments solicited from NHP experts)

that these animals need more ﬂoor and vertical space, at least in some

groups, to exercise their natural habits.

Chapter 4 discusses veterinary care and the responsibilities of the

attending veterinarian. It introduces the concept of animal biosecurity and

upholds its central role in ensuring the health of laboratory animals. The

chapter includes recommendations relative to animal procurement, trans-

portation, and preventive medicine, and expands the sections on clinical

care and management, surgery (with a new section on intraoperative moni-

toring), pain and distress, and euthanasia.

Chapter 5 discusses physical plant–related topics and includes updated

and new material on vibration control; physical security and access con-

trol; hazardous agent containment; and special facilities for imaging and

whole body irradiation, barrier housing, behavioral studies, and aquatic spe-

cies housing. The chapter provides detailed discussion of centralized versus

decentralized animal facilities and introduces the concept of variable-volume

HVAC systems with a nod toward energy conservation and efﬁciency.

Appendix A is the updated bibliography; Appendix B presents the U.S.

Government Principles for the Utilization and Care of Vertebrate Animals

Used in Testing, Research, and Training; Appendix C presents the Statement

OVERVIEW xix

of Task; and Appendix D provides the biographical sketches of the Com-

mittee members.

In accordance with the Statement of Task (“In addition to the published

report, the updated Guide will be posted on the Internet in a pdf or equiva-

lent format such that users will be able to search the entire document at

one time”), the Guide is available in searchable pdf format on the National

Academies Press website, www.nap.edu.

xxi

Contents

1 KEY CONCEPTS 1

Applicability and Goals, 2

Intended Audiences and Uses of the Guide, 3

Ethics and Animal Use, 4

The Three Rs, 4

Key Terms Used in the Guide, 5

Humane Care, 6

Animal Care and Use Program, 6

Engineering, Performance, and Practice Standards, 6

Policies, Principles, and Procedures, 7

Must, Should, and May, 8

References, 8

2 ANIMAL CARE AND USE PROGRAM 11

Regulations, Policies, and Principles, 12

Program Management, 13

Program Management Responsibility, 13

The Institutional Ofﬁcial, 13

The Attending Veterinarian, 14

The Institutional Animal Care and Use Committee, 14

Collaborations, 15

Personnel Management, 15

Training and Education, 15

Occupational Health and Safety of Personnel, 17

xxii CONTENTS

Personnel Security, 23

Investigating and Reporting Animal Welfare Concerns, 23

Program Oversight, 24

The Role of the IACUC, 24

IACUC Constitution and Function, 24

Protocol Review, 25

Special Considerations for IACUC Review, 27

Postapproval Monitoring, 33

Disaster Planning and Emergency Preparedness, 35

References, 35

3 ENVIRONMENT, HOUSING, AND MANAGEMENT 41

Terrestrial Animals, 42

Terrestrial Environment, 42

Microenvironment and Macroenvironment, 42

Temperature and Humidity, 43

Ventilation and Air Quality, 45

Illumination, 47

Noise and Vibration, 49

Terrestrial Housing, 50

Microenvironment (Primary Enclosure), 50

Environmental Enrichment, 52

Sheltered or Outdoor Housing, 54

Naturalistic Environments, 55

Space, 55

Terrestrial Management, 63

Behavioral and Social Management, 63

Husbandry, 65

Population Management, 75

Aquatic Animals, 77

Aquatic Environment, 77

Microenvironment and Macroenvironment, 77

Water Quality, 78

Life Support System, 79

Temperature, Humidity, and Ventilation, 80

Illumination, 81

Noise and Vibration, 81

Aquatic Housing, 82

Microenvironment (Primary Enclosure), 82

Environmental Enrichment and Social Housing, 82

Sheltered, Outdoor, and Naturalistic Housing, 83

Space, 83

CONTENTS xxiii

Aquatic Management, 84

Behavior and Social Management, 84

Husbandry, 84

Population Management, 87

References, 88

4 VETERINARY CARE 105

Animal Procurement and Transportation, 106

Animal Procurement, 106

Transportation of Animals, 107

Preventive Medicine, 109

Animal Biosecurity, 109

Quarantine and Stabilization, 110

Separation by Health Status and Species, 111

Surveillance, Diagnosis, Treatment, and Control of Disease, 112

Clinical Care and Management, 113

Medical Management, 114

Emergency Care, 114

Recordkeeping, 115

Surgery, 115

Training, 115

Presurgical Planning, 116

Surgical Facilities, 116

Surgical Procedures, 117

Aseptic Technique, 118

Intraoperative Monitoring, 119

Postoperative Care, 119

Pain and Distress, 120

Anesthesia and Analgesia, 121

Euthanasia, 123

References, 124

5 PHYSICAL PLANT 133

General Considerations, 133

Location, 134

Centralization Versus Decentralization, 134

Functional Areas, 135

Construction Guidelines, 136

Corridors, 136

Animal Room Doors, 137

Exterior Windows, 137

Floors, 137

xxiv CONTENTS

Drainage, 138

Walls and Ceilings, 138

Heating, Ventilation, and Air Conditioning (HVAC), 139

Power and Lighting, 141

Storage Areas, 141

Noise Control, 142

Vibration Control, 142

Facilities for Sanitizing Materials, 143

Environmental Monitoring, 143

Special Facilities, 144

Surgery, 144

Barrier Facilities, 145

Imaging, 146

Whole Body Irradiation, 147

Hazardous Agent Containment, 148

Behavioral Studies, 149

Aquatic Species Housing, 150

Security and Access Control, 151

References, 151

ADDENDUM 155

APPENDICES

A ADDITIONAL SELECTED REFERENCES 161

Subject Matter, 161

Use of Laboratory Animals, 162

Alternatives, 162

Ethics and Welfare, 163

Experimental Design and Statistics, 164

Research and Testing Methodology, 165

Program Management, 167

General References, 167

Laws, Regulations, and Policies, 168

Education, 169

Monitoring the Care and Use of Animals, 169

Occupational Health and Safety, 170

Environment, Housing, and Management, 172

General References, 172

Environmental Enrichment, 173

Genetics and Genetically Modiﬁed Animals, 175

CONTENTS xxv

Species-Speciﬁc References—Environment, Housing, and

Management, 176

Agricultural Animals, 176

Amphibians, Reptiles, and Fish, 178

Birds, 179

Cats and Dogs, 180

Exotic, Wild, and Zoo Animals, 181

Nonhuman Primates, 182

Rodents and Rabbits, 184

Other Animals, 187

Veterinary Care, 188

Transportation, 188

Anesthesia, Pain, and Surgery, 188

Disease Surveillance, Diagnosis, and Treatment, 190

Pathology, Clinical Pathology, and Parasitology, 190

Species-Speciﬁc References—Veterinary Care, 191

Agricultural Animals, 191

Amphibians, Reptiles, and Fish, 192

Birds, 193

Cats and Dogs, 193

Exotic, Wild, and Zoo Animals, 193

Nonhuman Primates, 194

Rodents and Rabbits, 194

Design and Construction of Animal Facilities, 196

B U.S. GOVERNMENT PRINCIPLES FOR THE UTILIZATION

AND CARE OF VERTEBRATE ANIMALS USED IN TESTING,

RESEARCH, AND TRAINING 199

C STATEMENT OF TASK 201

D ABOUT THE AUTHORS 203

INDEX 209

Key Concepts

his edition of the Guide for the Care and Use of Laboratory Animals

(the Guide) strongly afﬁrms the principle that all who care for, use,

or produce animals for research, testing, or teaching must assume

responsibility for their well-being. The Guide is created by scientists and

veterinarians for scientists and veterinarians to uphold the scientiﬁc rigor

and integrity of biomedical research with laboratory animals as expected

by their colleagues and society at large.

The Guide plays an important role in decision making regarding the

use of vertebrate laboratory animals because it establishes the minimum

ethical, practice, and care standards for researchers and their institutions.

The use of laboratory animals in research, teaching, testing, and production

is also governed or affected by various federal and local laws, regulations,

and standards; for example, in the United States the Animal Welfare Act

(AWA 1990) and Regulations (PL 89-544; USDA 1985) and/or Public Health

Service (PHS) Policy (PHS 2002) may apply. Compliance with these laws,

regulations, policies, and standards (or subsequent revised versions) in the

establishment and implementation of a program of animal care and use is

discussed in Chapter 2.

Taken together, the practical effect of these laws, regulations, and poli-

cies is to establish a system of self-regulation and regulatory oversight that

binds researchers and institutions using animals. Both researchers and insti-

tutions have afﬁrmative duties of humane care and use that are supported

by practical, ethical, and scientiﬁc principles. This system of self-regulation

establishes a rigorous program of animal care and use and provides ﬂex-

ibility in fulﬁlling the responsibility to provide humane care. The speciﬁc

2 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

scope and nature of this responsibility can vary based on the scientiﬁc

discipline, nature of the animal use, and species involved, but because it

affects animal care and use in every situation this responsibility requires

that producers, teachers, researchers, and institutions carry out purposeful

analyses of proposed uses of laboratory animals. The Guide is central to

these analyses and to the development of a program in which humane care

is incorporated into all aspects of laboratory animal care and use.

APPLICABILITY AND GOALS

In the Guide, laboratory animals (also referred to as animals) are gener-

ally deﬁned as any vertebrate animal (i.e., traditional laboratory animals,

agricultural animals, wildlife, and aquatic species) produced for or used

in research, testing, or teaching. Animal use is deﬁned as the proper care,

use, and humane treatment of laboratory animals produced for or used in

research, testing, or teaching.

Laboratory animals or animals:

Any vertebrate animal (e.g.,

traditional laboratory animals,

agricultural animals, wildlife, and

aquatic species) produced for

or used in research, testing, or

teaching.

Animal use: The proper care,

use, and humane treatment of

laboratory animals produced for

or used in research, testing, or

teaching.

When appropriate, considerations

or speciﬁc emphases for agricultural

animals and nontraditional species

are presented. The Guide does not

address in detail agricultural ani-

mals used in production, agricul-

tural research or teaching, wildlife

and aquatic species studied in natu-

ral settings, or invertebrate animals

(e.g., cephalopods) used in research,

but establishes general principles and ethical considerations that are also

applicable to these species and situations. References provide the reader

with additional resources, and supplemental information on breeding, care,

management, and use of selected

laboratory animal species is avail-

able in other publications prepared

by the Institute for Laboratory Animal

Research (ILAR) and other organiza-

tions (Appendix A).

The goal of the Guide is to pro-

mote the humane care and use of

laboratory animals by providing information that will enhance animal well-

being, the quality of research, and the advancement of scientiﬁc knowledge

that is relevant to both humans and animals. The Committee recognizes that

the use of different species in research is expanding and that researchers

and institutions will face new and unique challenges in determining how

to apply the Guide in these situations. In making such determinations, it is

KEY CONCEPTS 3

important to keep in mind that the Guide is intended to provide information

to assist researchers, institutional animal care and use committees (IACUCs),

veterinarians, and other stakeholders in ensuring the implementation of

effective and appropriate animal care and use programs that are based on

humane care. Throughout the Guide, scientists and institutions are encour-

aged to give careful and deliberate thought to the decision to use animals,

taking into consideration the contribution that such use will make to new

knowledge, ethical concerns, and the availability of alternatives to animal

use (NRC 1992). A practical strategy for decision making, the “Three Rs”

(Replacement, Reduction, and Reﬁnement) approach, is discussed in more

detail below. Institutions should use the recommendations in the Guide as

a foundation for the development of a comprehensive animal care and use

program and a process for continually improving this program.

INTENDED AUDIENCES AND USES OF THE Guide

The Guide is intended for a wide and diverse audience, including

• the scientiﬁc community

• administrators

• IACUCs

• veterinarians

• educators and trainers

• producers of laboratory animals

• accreditation bodies

• regulators

• the public.

The Guide is meant to be read by the user in its entirety, as there are

many concepts throughout that may be helpful. Individual sections will

be particularly relevant to certain users, and it is expected that the reader

will explore in more detail the references provided (including those in

Appendix A) on topics of interest.

Members of the scientiﬁc community (investigators and other animal

users) will ﬁnd Chapters 1 and 2 (and portions of Chapter 4) of the Guide

useful for their interactions with the IACUC, attending veterinarian, and

administrators regarding animal care as well as the preparation of animal

care and use protocols. Scientiﬁc review committees and journal editors

may choose to refer to multiple sections of the Guide to determine whether

scientists contributing proposals and manuscripts have met the appropriate

standards in their planned use of animals. The Guide can assist IACUCs

and administrators in protocol review, assessment, and oversight of an ani-

mal care and use program. Veterinarians should ﬁnd Chapters 3 through 5

4 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

valuable for their oversight and support of animal care and use. Educators

and trainers can use the Guide as a document to assess both the scope and

adequacy of training programs supported by the institution. Accreditation

bodies will ﬁnd the Guide useful for evaluating many areas of animal care

and use programs not subject to strict engineering standards (see deﬁnition

below). Finally, members of the public should feel assured that adherence

to the Guide will ensure humane care and use of laboratory animals.

Readers are reminded that the Guide is used by a diverse group of

national and international institutions and organizations, many of which are

covered by neither the Animal Welfare Act nor the PHS Policy. The Guide

uses some terminology that is both deﬁned by US statute and denotes a

general concept (e.g., “attending veterinarian,” “adequate veterinary care,”

and “institutional ofﬁcial”). Even if these terms are not consistent with those

used by non-US institutions, the underlying principles can still be applied.

In all instances where Guide recommendations are different from applicable

legal or policy requirements, the higher standard should apply.

ETHICS AND ANIMAL USE

The decision to use animals in research requires critical thought, judg-

ment, and analysis. Using animals in research is a privilege granted by society

to the research community with the expectation that such use will provide

either signiﬁcant new knowledge or lead to improvement in human and/or

animal well-being (McCarthy 1999; Perry 2007). It is a trust that mandates

responsible and humane care and use of these animals. The Guide endorses

the responsibilities of investigators as stated in the U.S. Government Principles

for Utilization and Care of Vertebrate Animals Used in Testing, Research, and

Training (IRAC 1985; see Appendix B). These principles direct the research

community to accept responsibility for the care and use of animals during all

phases of the research effort. Other government agencies and professional

organizations have published similar principles (NASA 2008; NCB 2005; NIH

2006, 2007; for additional references see Appendix A). Ethical considerations

discussed here and in other sections of the Guide should serve as a starting

point; readers are encouraged to go beyond these provisions. In certain situ-

ations, special considerations will arise during protocol review and planning;

several of these situations are discussed in more detail in Chapter 2.

THE THREE Rs

The Three Rs represent a practical method for implementation of the prin-

ciples described above. In 1959, W.M.S. Russell and R.L. Burch published

a practical strategy of replacement, reﬁnement, and reduction—referred to

as the Three Rs—for researchers to apply when considering experimental

KEY CONCEPTS 5

design in laboratory animal research (Russell and Burch 1959). Over the

years, the Three Rs have become an internationally accepted approach

for researchers to apply when deciding to use animals in research and in

designing humane animal research studies.

Replacement refers to methods that avoid using animals. The term

includes absolute replacements (i.e., replacing animals with inanimate

systems such as computer programs) as well as relative replacements (i.e.,

replacing animals such as vertebrates with animals that are lower on the

phylogenetic scale).

Reﬁnement refers to modiﬁcations of husbandry or experimental pro-

cedures to enhance animal well-being and minimize or eliminate pain

and distress. While institutions and investigators should take all reasonable

measures to eliminate pain and distress through reﬁnement, IACUCs should

understand that with some types of studies there may be either unforeseen

or intended experimental outcomes that produce pain. These outcomes may

or may not be eliminated based on the goals of the study.

Reduction involves strategies for obtaining comparable levels of infor-

mation from the use of fewer animals or for maximizing the information

obtained from a given number of animals (without increasing pain or dis-

tress) so that in the long run fewer animals are needed to acquire the same

scientiﬁc information. This approach relies on an analysis of experimental

design, applications of newer technologies, the use of appropriate statisti-

cal methods, and control of environmentally related variability in animal

housing and study areas (see Appendix A).

Reﬁnement and reduction goals should be balanced on a case-by-case

basis. Principal investigators are strongly discouraged from advocating ani-

mal reuse as a reduction strategy, and reduction should not be a rationale

for reusing an animal or animals that have already undergone experimental

procedures especially if the well-being of the animals would be compro-

mised. Studies that may result in severe or chronic pain or signiﬁcant altera-

tions in the animals’ ability to maintain normal physiology, or adequately

respond to stressors, should include descriptions of appropriate humane

endpoints or provide science-based justiﬁcation for not using a particular,

commonly accepted humane endpoint. Veterinary consultation must occur

when pain or distress is beyond the level anticipated in the protocol descrip-

tion or when interventional control is not possible.

KEY TERMS USED IN THE Guide

The Committee for the Update of the Guide believes that the terms set

out below are important for a full understanding of the Guide. Accordingly,

we have deﬁned these terms and concepts to provide users of the Guide

with additional assistance in implementing their responsibilities.

6 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

Humane Care

Humane care means those actions taken to ensure that laboratory

animals are treated according to high ethical and scientiﬁc standards.

Implementation of a humane care program, and creation of a laboratory

environment in which humane care and respect for animals are valued and

encouraged, underlies the core requirements of the Guide and the system

of self-regulation it supports (Klein and Bayne 2007).

Animal Care and Use Program

The animal care and use program (the Program) means the policies,

procedures, standards, organizational structure, stafﬁng, facilities, and prac-

tices put into place by an institution to achieve the humane care and use

of animals in the laboratory and throughout the institution. It includes the

establishment and support of an IACUC or equivalent ethical oversight com-

mittee and the maintenance of an environment in which the IACUC can

function successfully to carry out its responsibilities under the Guide and

applicable laws and policies. Chapter 2 provides a more expansive discus-

sion of the importance of the Guide and its application to animal care and

use programs.

Engineering, Performance, and Practice Standards

Engineering standard means a standard or guideline that speciﬁes in detail a

method, technology, or technique for achieving a desired outcome; it does

not provide for modiﬁcation in the event that acceptable alternative meth-

ods are available or unusual circumstances arise. Engineering standards are

prescriptive and provide limited ﬂexibility for implementation. However, an

engineering standard can be useful to establish a baseline and is relatively

easy to use in evaluating compliance.

Performance standard means a standard or guideline that, while describing a

desired outcome, provides ﬂexibility in achieving this outcome by granting

discretion to those responsible for managing the animal care and use pro-

gram, the researcher, and the IACUC. The performance approach requires

professional input, sound judgment, and a team approach to achieve spe-

ciﬁc goals. It is essential that the desired outcomes and/or goals be clearly

deﬁned and appropriate performance measures regularly monitored in order

to verify the success of the process. Performance standards can be advan-

tageous because they accommodate the consideration of many variables

(such as the species and previous history of the animals, facilities, staff

KEY CONCEPTS 7

expertise, and research goals) so that implementation can be best tailored

to meet the recommendations in the Guide.

Ideally, engineering and performance standards are balanced, setting a

target for optimal practices, management, and operations while encourag-

ing ﬂexibility and judgment, if appropriate, based on individual situations

(Gonder et al. 2001).

Scientists, veterinarians, technicians, and others have extensive experi-

ence and information covering many of the topics discussed in the Guide.

For topics on which information is insufﬁcient or incomplete, sustained

research into improved methods of laboratory animal management, care,

and use is needed for the continued evaluation and improvement of perfor-

mance and engineering standards.

Practice standard means the application of professional judgment by quali-

ﬁed, experienced individuals to a task or process over time, an approach

that has been demonstrated to beneﬁt or enhance animal care and use. Pro-

fessional judgment comes from information in the peer-reviewed scientiﬁc

literature and textbooks and, as in many other disciplines, from time-proven

experiences in the ﬁeld (for additional information see Chapter 2). In the

absence of published scientiﬁc literature or other deﬁnitive sources, where

experience has demonstrated that a particular practice improves animal

care and use, practice standards have been used in determining appropriate

recommendations in the Guide. In most situations, the Guide is intended to

provide ﬂexibility so that institutions can modify practices and procedures

with changing conditions and new information.

POLICIES, PRINCIPLES, AND PROCEDURES

Policies commonly derive from a public agency or private entity. They

are generally practical statements of collective wisdom, convention, or

management direction that are internal to the entity. However, policies may

assume broader force when they become the means by which an imple-

menting agency interprets existing statutes (e.g., PHS Policy). Principles

are broader in their scope and intended application, and are accepted

generalizations about a topic that are frequently endorsed by many and

diverse organizations (e.g., the U.S. Government Principles). Procedures

(often called “operating procedures” or “standard operating procedures”)

are typically detailed, step-by-step processes meant to ensure the consistent

application of institutional practices. Establishing standard operating proce-

dures can assist an institution in complying with regulations, policies, and

principles as well as with day-to-day operations and management.

8 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

MUST, SHOULD, AND MAY

Must indicates actions that the Committee for the Update of the Guide

considers imperative and mandatory duty or requirement for providing

humane animal care and use. Should indicates a strong recommendation

for achieving a goal; however, the Committee recognizes that individual

circumstances might justify an alternative strategy. May indicates a sugges-

tion to be considered.

The Guide is written in general terms so that its recommendations can

be applied in diverse institutions and settings that produce or use animals for

research, teaching, and testing. This approach requires that users, IACUCs,

veterinarians, and producers apply professional judgment in making speciﬁc

decisions regarding animal care and use. Because the Guide is written in

general terms, IACUCs have a key role in interpretation, implementation,

oversight, and evaluation of institutional animal care and use programs.

REFERENCES

AWA [Animal Welfare Act]. 1990. Animal Welfare Act. PL (Public Law) 89-544. Available at

www.nal.usda.gov/awic/legislat/awa.htm; accessed January 14, 2010.

Gonder JC, Smeby RR, Wolﬂe TL. 2001. Performance Standards and Animal Welfare: Deﬁni-

tion, Application and Assessment, Parts I and II. Greenbelt MD: Scientists Center for

Animal Welfare.

IRAC [Interagency Research Animal Committee]. 1985. U.S. Government Principles for Utili-

zation and Care of Vertebrate Animals Used in Testing, Research, and Training. Federal

at http://oacu.od.nih.gov/regs/USGovtPrncpl.htm; accessed May 10, 2010.

Klein HJ, Bayne KA. 2007. Establishing a culture of care, conscience, and responsibility:

Addressing the improvement of scientiﬁc discovery and animal welfare through science-

based performance standards. ILAR J 48:3-11.

McCarthy CR. 1999. Bioethics of laboratory animal research. ILAR J 40:1-37.

NASA [National Aeronautics and Space Administration]. 2008. NASA Principles for the Ethical

Care and Use of Animals. NPR 8910.1B-Appendix A. May 28. Available at http://nodis3.

gsfc.nasa.gov/displayDir.cfm?t=NPDandc=8910ands=1B; accessed May 10, 2010.

NCB [Nufﬁeld Council on Bioethics]. 2005. The Ethics of Research Using Animals. London:

NCB.

NIH [National Institutes of Health]. 2007. Memorandum of Understanding Between the Ofﬁce

of Laboratory Animal Welfare, National Institutes of Health, US Department of Health and

Human Services and the Ofﬁce of Research Oversight and the Ofﬁce of Research and De-

velopment, Veterans Health Administration, US Department of Veterans Affairs Concerning

Laboratory Animal Welfare. November 2007. Bethesda: Ofﬁce of Extramural Research, NIH.

Available at http://grants.nih.gov/grants/olaw/references/mou_olaw_va_2007_11.htm.

NIH. 2006. Memorandum of Understanding Among the Animal and Plant Health Inspection

Service USDA and the Food and Drug Administration, US Department of Health and

Human Services, and the National Institutes of Health Concerning Laboratory Animal

Welfare. March 1, 2006. Bethesda: Ofﬁce of Extramural Research, NIH. Available at

http://grants.nih.gov/grants/olaw/references/ﬁnalmou.htm.

KEY CONCEPTS 9

NRC [National Research Council]. 1992. Report on Responsible Science. Washington: Na-

tional Academy Press.

Perry P. 2007. The ethics of animal research: A UK perspective. ILAR J 48:42-46.

PHS [Public Health Service]. 2002. Public Health Service Policy on Humane Care and Use of

Laboratory Animals. Publication of the Department of Health and Human Services, Na-

tional Institutes of Health, Ofﬁce of Laboratory Animal Welfare. Available at http://grants.

nih.gov/grants/olaw/references/phspol.htm; accessed June 9, 2010.

Russell WMS, Burch RL. 1959. The Principles of Humane Experimental Technique. London:

Methuen and Co. [Reissued: 1992, Universities Federation for Animal Welfare, Herts,

UK].

USDA [US Department of Agriculture]. 1985. 9 CFR 1A. (Title 9, Chapter 1, Subchapter A):

Animal Welfare. Available at http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?sid=8314313bd

7adf2c9f1964e2d82a88d92andc=ecfrandtpl=/ecfrbrowse/Title09/9cfrv1_02.tpl; accessed

January 14, 2010.

Animal Care and Use Program

he proper care and use of laboratory animals in research, testing,

teaching, and production (animal use) require scientiﬁc and profes-

sional judgment based on the animals’ needs and their intended

use. An animal care and use program

(hereafter referred to as the Program)

comprises all activities conducted by

and at an institution that have a direct

impact on the well-being of animals,

including animal and veterinary care,

policies and procedures, personnel

and program management and over-

sight, occupational health and safety,

institutional animal care and use com-

mittee (IACUC) functions, and animal

facility design and management.

This chapter deﬁnes the overall

Program and key oversight responsi-

bilities and provides guidelines to aid in developing an effective Program.

Chapters 3, 4, and 5 cover the details of Program components: environment,

housing, and management; veterinary care; and physical plant, respectively.

Each institution should establish and provide sufﬁcient resources for a Pro-

gram that is managed in accord with the Guide and in compliance with

applicable regulations, policies, and guidelines.

Program: The activities con-

ducted by and at an institution

that have a direct impact on the

well-being of animals, including

animal and veterinary care, poli-

cies and procedures, personnel

and program management and

oversight, occupational health

and safety, IACUC functions,

and animal facility design and

management.

12 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

REGULATIONS, POLICIES, AND PRINCIPLES

The use of laboratory animals is governed by an interrelated, dynamic

system of regulations, policies, guidelines, and procedures. The Guide

takes into consideration regulatory requirements relevant to many US-based

activities, including the Animal Welfare Regulations (USDA 1985; US Code,

42 USC § 289d) and the Public Health Service Policy on Humane Care and

Use of Laboratory Animals (PHS 2002). The use of the Guide by non-US

entities also presumes adherence to all regulations relevant to the humane

care and use of laboratory animals applicable in those locations. The Guide

also takes into account the U.S. Government Principles for Utilization and

Care of Vertebrate Animals Used in Testing, Research, and Training (IRAC

1985; see Appendix B) and endorses the following principles:

• consideration of alternatives (in vitro systems, computer simula-

tions, and/or mathematical models) to reduce or replace the use of

animals

• design and performance of procedures on the basis of relevance to

human or animal health, advancement of knowledge, or the good

of society

• use of appropriate species, quality, and number of animals

• avoidance or minimization of discomfort, distress, and pain

• use of appropriate sedation, analgesia, and anesthesia

• establishment of humane endpoints

• provision of adequate veterinary care

• provision of appropriate animal transportation and husbandry

directed and performed by qualiﬁed persons

• conduct of experimentation on living animals exclusively by

and/or under the close supervision of qualiﬁed and experienced

personnel.

Interpretation and application of these principles and the Guide require

knowledge, expertise, experience, and professional judgment. Programs

should be operated in accord with the Guide and relevant regulations,

policies, and principles. Also, institutions are encouraged to establish and

periodically review written procedures to ensure consistent application of

Guide standards. Supplemental information on various aspects of animal

care and use is available in other publications prepared by the Institute for

Laboratory Animal Research (ILAR) and other organizations (Appendix A).

References in the Guide provide the reader with additional information

that supports statements made in the Guide. In the absence of published

literature, some information in the Guide is derived from currently accepted

practice standards in laboratory animal science (see Chapter 1). The body

ANIMAL CARE AND USE PROGRAM 13

of literature related to animal science and use of animals is constantly

evolving, requiring Programs to remain current with the information and

best practices.

PROGRAM MANAGEMENT

An effective Program requires clearly deﬁned roles that align respon-

sibility with regulatory and management authority. US federal law creates

a statutory basis for the institutional ofﬁcial (IO), the attending veterinarian

(AV), and the institutional animal care and use committee (IACUC). The

Guide endorses these concepts as important operating principles for all US

and non-US animal care and use programs. Effective leadership in and col-

laboration among these three components, which not only oversee but also

support animal users, are necessary (Lowman 2008; Van Sluyters 2008). In

addition, interactions with regulatory and funding agencies and accredita-

tion organizations are an integral part of the Program.

As summarized here and discussed throughout the Guide, the primary

oversight responsibilities in the Program rest with the IO, the AV, and the

IACUC. Their roles ﬁt in a deﬁned organizational structure where the

reporting relationships, authorities, and responsibilities of each are clearly

deﬁned and transparent. Together they establish policies and procedures,

ensure regulatory compliance, monitor Program performance, and support

high-quality science and humane animal use. A Program that includes these

elements and establishes a balance among them has the best chance of efﬁ-

ciently using resources while attaining the highest standards of animal well-

being and scientiﬁc quality (Bayne and Garnett 2008; Van Sluyters 2008).

Program Management Responsibility

The Institutional Ofﬁcial

Institutional ofﬁcial: The indi-

vidual who, as a representative

of senior administration, bears

ultimate responsibility for the

Program and is responsible for

resource planning and ensuring

alignment of Program goals with

the institution’s mission.

The institutional ofﬁcial (IO) bears ultimate responsibility for the Pro-

gram, although overall Program direction should be a shared responsibility

among the IO, AV, and IACUC. The

IO has the authority to allocate the

resources needed to ensure the Pro-

gram’s overall effectiveness. Program

needs should be clearly and regularly

communicated to the IO by the AV,

the IACUC, and others associated

with the Program (e.g., facilities man-

agement staff, occupational health

and safety personnel, scientists). As a

14 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

representative of senior administration, the IO is responsible for resource

planning and ensuring the alignment of Program goals of quality animal

care and use with the institution’s mission.

The Attending Veterinarian

Attending veterinarian: The

veterinarian responsible for

the health and well-being of all

laboratory animals used at the

institution.

The attending veterinarian (AV) is responsible for the health and well-

being of all laboratory animals used at the institution. The institution must

provide the AV with sufﬁcient authority, including access to all animals,

and resources to manage the program

of veterinary care. The AV should

oversee other aspects of animal care

and use (e.g., husbandry, housing)

to ensure that the Program complies

with the Guide.

Institutional mission, program-

matic goals, including the nature of

animal use at the institution, and Program size will determine whether full-

time, part-time, or consultative veterinary services are needed. If a full-time

veterinarian is not available on site, a consulting or part-time veterinarian

should be available in visits at intervals appropriate to programmatic needs.

In such instances, there must be an individual with assigned responsibility

for daily animal care and use and facility management. While institutions

with large animal care and use programs may employ multiple veterinar-

ians, the management of veterinary medicine, animal care, and facility

operations by a single administrative unit is often an efﬁcient mechanism

to administer all aspects of the Program.

The Guide endorses the American College of Laboratory Animal Medi-

cine’s (ACLAM) “Guidelines for Adequate Veterinary Care” (ACLAM 1996).

These guidelines include veterinary access to all animals and their medical

records, regular veterinary visits to facilities where animals are or may be

housed or used, provisions for appropriate and competent clinical, preven-

tive, and emergency veterinary care, and a system for legal animal procure-

ment and transportation. Other responsibilities of the AV are outlined in the

Program Oversight section below and in later chapters. For a Program to

work effectively, there should be clear and regular communication between

the AV and the IACUC.

The Institutional Animal Care and Use Committee

The IACUC (or institutional equivalent) is responsible for assessment

and oversight of the institution’s Program components and facilities. It

should have sufﬁcient authority and resources (e.g., staff, training, comput-

ANIMAL CARE AND USE PROGRAM 15

ers and related equipment) to fulﬁll this responsibility. Detailed information

on the role and function of the IACUC is provided later in this chapter.

Collaborations

Interinstitutional collaboration has the potential to create ambiguities

about responsibility for animal care and use. In cases of such collaboration

involving animal use (beyond animal transport), the participating institutions

should have a formal written understanding (e.g., a contract, memorandum

of understanding, or agreement) that addresses the responsibility for offsite

animal care and use, animal ownership, and IACUC review and oversight

(AAALAC 2003). In addition, IACUCs from the participating institutions may

choose to review protocols for the work being conducted.

Personnel Management

Training and Education

All personnel involved with the care and use of animals must be ade-

quately educated, trained, and/or qualiﬁed in basic principles of laboratory

animal science to help ensure high-quality science and animal well-being.

The number and qualiﬁcations of personnel required to conduct and sup-

port a Program depend on several factors, including the type and size of

the institution, the administrative structure for providing adequate animal

care, the characteristics of the physical plant, the number and species of

animals maintained, and the nature of the research, testing, teaching, and

production activities. Institutions are responsible for providing appropriate

resources to support personnel training (Anderson 2007), and the IACUC

is responsible for providing oversight and for evaluating the effectiveness

of the training program (Foshay and Tinkey 2007). All Program personnel

training should be documented.

Veterinary and Other Professional Staff Veterinarians providing clinical

and/or Program oversight and support must have the experience, training,

and expertise necessary to appropriately evaluate the health and well-

being of the species used in the context of the animal use at the institu-

tion. Veterinarians providing broad Program direction should be trained or

have relevant experience in laboratory animal facility administration and

management. Depending on the scope of the Program, professionals with

expertise in other speciﬁc areas may be needed—in, for example, facility

design and renovation, human resource management, pathology of labora-

tory animals, comparative genomics, facility and equipment maintenance,

diagnostic laboratory operations, and behavioral management. Laboratory

16 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

animal science and medicine are rapidly changing and evolving disciplines.

The institution should provide opportunities and support for regular profes-

sional development and continuing education to ensure both that profes-

sional staff are knowledgeable about the latest practices and procedures and

that laboratory animals receive high-quality care (Colby et al. 2007).

Animal Care Personnel Personnel caring for animals should be appropri-

ately trained (see Appendix A, Education), and the institution should provide

for formal and/or on-the-job training to facilitate effective implementation of

the Program and the humane care and use of animals. Staff should receive

training and/or have the experience to complete the tasks for which they

are responsible. According to the Program scope, personnel with expertise

in various disciplines (e.g., animal husbandry, administration, veterinary

medical technology) may be required.

There are a number of options for training animal care personnel and

technicians (Pritt and Duffee 2007). Many colleges have accredited pro-

grams in veterinary technology (AVMA 2010); most are 2-year programs

that award Associate of Science degrees, some are 4-year programs that

award Bachelor of Science degrees. Nondegree training, via certiﬁcation

programs for laboratory animal technicians and technologists, is available

from the American Association for Laboratory Animal Science (AALAS), and

there are various commercially available training materials appropriate for

self-guided study (Appendix A).

Personnel caring for laboratory animals should also regularly engage in

continuing education activities and should be encouraged to participate in

local and national laboratory animal science meetings and in other relevant

professional organizations. On-the-job training, supplemented with institu-

tion-sponsored discussion and training programs and reference materials

applicable to their jobs and the species in their care, should be provided to

each employee responsible for animal care (Kreger 1995).

Coordinators of institutional training programs can seek assistance from

the Animal Welfare Information Center (AWIC), the Laboratory Animal

Welfare and Training Exchange (LAWTE), AALAS, and ILAR (NRC 1991).

The Guide to the Care and Use of Experimental Animals by the Canadian

Council on Animal Care (CCAC 1993) and guidelines from other coun-

tries are valuable additions to the libraries of laboratory animal scientists

(Appendix A).

The Research Team The institution should provide appropriate education

and training to members of research teams—including principal investiga-

tors, study directors, research technicians, postdoctoral fellows, students,

and visiting scientists—to ensure that they have the necessary knowledge

and expertise for the speciﬁc animal procedures proposed and the species

ANIMAL CARE AND USE PROGRAM 17

used (Conarello and Shepard 2007). Training should be tailored to the

particular needs of research groups; however, all research groups should

receive training in animal care and use legislation, IACUC function, eth-

ics of animal use and the concepts of the Three Rs, methods for reporting

concerns about animal use, occupational health and safety issues pertaining

to animal use, animal handling, aseptic surgical technique, anesthesia and

analgesia, euthanasia, and other subjects, as required by statute. Continu-

ing education programs should be offered to reinforce training and provide

updates that reﬂect changes in technology, legislation, and other relevant

areas. Frequency of training opportunities should ensure that all animal

users have adequate training before beginning animal work.

The IACUC It is the institution’s responsibility to ensure that IACUC mem-

bers are provided with training opportunities to understand their work

and role. Such training should include formal orientation to introduce

new members to the institution’s Program; relevant legislation, regulations,

guidelines, and policies; animal facilities and laboratories where animal use

occurs; and the processes of animal protocol and program review (Greene

et al. 2007). Ongoing opportunities to enhance their understanding of ani-

mal care and use in science should also be provided. For example, IACUC

members may meet with animal care personnel and research teams; be

provided access to relevant journals, materials, and web-based training; and

be given opportunities to attend meetings or workshops.

Occupational Health and Safety of Personnel

Each institution must establish and maintain an occupational health and

safety program (OHSP) as an essential part of the overall Program of animal

care and use (CFR 1984a,b,c; DHHS 2009; PHS 2002). The OHSP must

be consistent with federal, state, and local regulations and should focus on

maintaining a safe and healthy workplace (Gonder 2002; Newcomer 2002;

OSHA 1998a). The nature of the OHSP will depend on the facility, research

activities, hazards, and animal species involved. The National Research

Council’s publication Occupational Health and Safety in the Care and

Use of Research Animals (NRC 1997) contains guidelines and references

for establishing and maintaining an effective, comprehensive OHSP (also

see Appendix A). An effective OHSP requires coordination between the

research program (as represented by the investigator), the animal care and

use Program (as represented by the AV, IO, and IACUC), the environmental

health and safety program, occupational health services, and administration

(e.g., human resources, ﬁnance, and facility maintenance personnel). Estab-

lishment of a safety committee may facilitate communication and promote

ongoing evaluation of health and safety in the workplace. In some cases

18 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

there is a regulatory requirement for such a committee. Operational and

day-to-day responsibility for safety in the workplace resides with the labora-

tory or facility supervisor (e.g., principal investigator, facility director, or a

staff veterinarian) and depends on safe work practices by all employees.

Control and Prevention Strategies A comprehensive OHSP should include a

hierarchy of control and prevention strategies that begins with the identiﬁ-

cation of hazards and the assessment of risk associated with those hazards.

Managing risk involves the following steps: ﬁrst, the appropriate design and

operation of facilities and use of appropriate safety equipment (engineering

controls); second, the development of processes and standard operating

procedures (SOPs; administrative controls); and ﬁnally, the provision of

appropriate personal protective equipment (PPE) for employees. Special

safety equipment should be used in combination with appropriate manage-

ment and safety practices (NIH 2002; OSHA 1998a,b). Managing risk using

these strategies requires that personnel be trained, maintain good personal

hygiene, be knowledgeable about the hazards in their work environment,

understand the proper selection and use of equipment, follow established

procedures, and use the PPE provided.

Hazard Identiﬁcation and Risk Assessment The institutional OHSP should

identify potential hazards in the work environment and conduct a critical

assessment of the associated risks. An effective OHSP ensures that the risks

associated with the experimental use of animals are identiﬁed and reduced to

minimal and acceptable levels. Hazard identiﬁcation and risk assessment are

ongoing processes that involve individuals qualiﬁed to assess dangers associ-

ated with the Program and implement commensurate safeguards. Health and

safety specialists with knowledge in relevant disciplines should be involved in

risk assessment and the development of procedures to manage such risks.

Potential hazards include experimental hazards such as biologic agents

(e.g., infectious agents or toxins), chemical agents (e.g., carcinogens and

mutagens), radiation (e.g., radionuclides, X-rays, lasers), and physical haz-

ards (e.g., needles and syringes). The risks associated with unusual experi-

mental conditions such as those encountered in ﬁeld studies or wildlife

research should also be addressed. Other potential hazards—such as animal

bites, exposure to allergens, chemical cleaning agents, wet ﬂoors, cage

washers and other equipment, lifting, ladder use, and zoonoses—that are

inherent in or intrinsic to animal use should be identiﬁed and evaluated.

Once potential hazards have been identiﬁed, a critical ongoing assessment

of the associated risks should be conducted to determine appropriate strate-

gies to minimize or manage the risks.

The extent and level of participation of personnel in the OHSP should

be based on the hazards posed by the animals and materials used (the

ANIMAL CARE AND USE PROGRAM 19

severity or seriousness of the hazard); the exposure intensity, duration, and

frequency (prevalence of the hazard); to some extent, the susceptibility (e.g.,

immune status) of the personnel; and the history of occupational illness and

injury in the particular workplace (Newcomer 2002; NRC 1997). Ongoing

identiﬁcation and evaluation of hazards call for periodic inspections and

reporting of potential hazardous conditions or “near miss” incidents.

Facilities, Equipment, and Monitoring The facilities required to support

the OHSP will vary depending on the scope and activities of the Program.

Their design should preferentially use engineering controls and equipment

to minimize exposure to anticipated hazards (also see Chapter 5). Because

a high standard of personal cleanliness is essential, changing, washing,

and showering facilities and supplies appropriate to the Program should

be available.

Where biologic agents are used, the Centers for Disease Control and

Prevention (CDC) and National Institutes of Health (NIH) publication Bio-

safety in Microbiological and Biomedical Laboratories (BMBL; DHHS 2009)

and the USDA standards (USDA 2002) should be consulted for appropriate

facility design and safety procedures. These design and safety features are

based on the level of risk posed by the agents used. Special facilities and

safety equipment may be needed to protect the animal care and investi-

gative staff, other occupants of the facility, the public, animals, and the

environment from exposure to hazardous biologic, chemical, and physical

agents used in animal experimentation (DHHS 2009; Frasier and Talka

2005; NIH 2002). When necessary, these facilities should be separated from

other animal housing and support areas, research and clinical laboratories,

and patient care facilities. They should be appropriately identiﬁed and

access to them limited to authorized personnel.

Facilities, equipment, and procedures should also be designed, selected,

and developed to reduce the possibility of physical injury or health risk

to personnel (NIOSH 1997a,b). Engineering controls and equipment that

address the risk of ergonomic injury in activities such as the lifting of heavy

equipment or animals should be considered (AVMA 2008). Those are also

frequently used to limit or control personnel exposure to animal allergens

(Harrison 2001; Huerkamp et al. 2009). The potential for repetitive motion

injuries in animal facilities (e.g., maintenance of large rodent populations

and other husbandry activities) should also be assessed.

The selection of appropriate animal housing systems requires profes-

sional knowledge and judgment and depends on the nature of the hazards

in question, the types of animals used, the limitations or capabilities of the

facilities, and the design of the experiments. Experimental animals should

be housed so that possibly contaminated food and bedding, feces, and urine

can be handled in a controlled manner. Appropriate facilities, equipment,

20 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

and procedures should be used for bedding disposal. Safety equipment

should be properly maintained and its function periodically validated.

Appropriate methods should be used for assessing and monitoring exposure

to potentially hazardous biologic, chemical, and physical agents where

required (e.g., ionizing radiation) or where the possibility of exceeding

permissible exposure limits exists (CFR 1984b).

Personnel Training As a general rule, safety depends on trained personnel

who rigorously follow safe practices. Personnel at risk should be provided

with clearly deﬁned procedures and, in speciﬁc situations, personal pro-

tective equipment to safely conduct their duties, understand the hazards

involved, and be proﬁcient in implementing the required safeguards. They

should be trained regarding zoonoses, chemical, biologic, and physical

hazards (e.g., radiation and allergies), unusual conditions or agents that

might be part of experimental procedures (e.g., the use of human tissue

in immunocompromised animals), handling of waste materials, personal

hygiene, the appropriate use of PPE, and other considerations (e.g., pre-

cautions to be taken during pregnancy, illness, or immunosuppression) as

appropriate to the risk imposed by their workplace.

Personal Hygiene The use of good personal hygiene will often reduce the

possibility of occupational injury and cross contamination. Appropriate

policies should be established and enforced, and the institution should

supply suitable attire and PPE (e.g., gloves, masks, face shields, head covers,

coats, coveralls, shoes or shoe covers) for use in the animal facility and

laboratories in which animals are used. Soiled attire should be disposed of,

laundered, or decontaminated by the institution as appropriate, and may

require that special provisions be implemented if outside vendors are used.

Personnel should wash and/or disinfect their hands and change clothing as

often as necessary to maintain good personal hygiene. Outer garments worn

in the animal rooms should not be worn outside the animal facility unless

covered (NRC 1997). Personnel should not be permitted to eat, drink, use

tobacco products, apply cosmetics, or handle or apply contact lenses in

rooms and laboratories where animals are housed or used (DHHS 2009;

NRC 1997; OSHA 1998a).

Animal Experimentation Involving Hazards When selecting speciﬁc safe-

guards for animal experimentation with hazardous agents, careful attention

should be given to procedures for animal care and housing, storage and

distribution of the agents, dose preparation and administration, body ﬂuid

and tissue handling, waste and carcass disposal, items that might be used

temporarily and removed from the site (e.g., written records, experimental

devices, sample vials), and personal protection.

ANIMAL CARE AND USE PROGRAM 21

Institutions should have written policies and procedures governing

experimentation with hazardous biologic, chemical, and physical agents.

An oversight process (such as the use of a safety committee) should be

developed to involve persons who are knowledgeable in the evaluation and

safe use of hazardous materials or procedures and should include review of

the procedures and facilities to be used for speciﬁc safety concerns. Formal

safety programs should be established to assess hazards, determine the

safeguards needed for their control, and ensure that staff have the necessary

training and skills and that facilities are adequate for the safe conduct of

the research. Technical support should be provided to monitor and ensure

compliance with institutional safety policies. A collaborative approach

involving the investigator and research team, attending veterinarian, ani-

mal care technician, and occupational health and safety professionals may

enhance compliance.

The BMBL (DHHS 2009) and NRC (1997) recommend practices and

procedures, safety equipment, and facility requirements for working with

hazardous biologic agents and materials. Facilities that handle agents of

unknown risk should consult with appropriate CDC personnel about haz-

ard control and medical surveillance. The use of highly pathogenic “select

agents and toxins” in research requires that institutions develop a program

and procedures for procuring, maintaining, and disposing of these agents

(CFR 1998, 2002a,b; NRC 2004; PL 107-56; PL 107-188; Richmond et al.

2003). The use of immunodeﬁcient or genetically modiﬁed animals (GMAs)

susceptible to or shedding human pathogens, the use of human tissues and

cell lines, or any infectious disease model can lead to an increased risk to

the health and safety of personnel working with the animals (Lassnig et al.

2005; NIH 2002).

Hazardous agents should be contained in the study environment, for

example through the use of airﬂow control during the handling and admin-

istering of hazardous agents, necropsies on contaminated animals (CDC

and NIH 2000), and work with chemical hazards (Thomann 2003). Waste

anesthetic gases should be scavenged to limit exposure.

Personal Protection While engineering and administrative controls are the

ﬁrst considerations for the protection of personnel, PPE appropriate for the

work environment, including clean institution-issued protective clothing,

should be provided as often as necessary. Protective clothing and equipment

should not be worn beyond the boundary of the hazardous agent work area

or the animal facility (DHHS 2009). If appropriate, personnel should shower

when they leave the animal care, procedure, or dose preparation areas.

Personnel with potential exposure to hazardous agents or certain species

should be provided with PPE appropriate to the situation (CFR 1984c); for

example, personnel exposed to nonhuman primates should have PPE such

22 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

as gloves, arm protectors, suitable face masks, face shields, and goggles

(NRC 2003a). Hearing protection should be available in high-noise areas

(OSHA 1998c). Personnel working in areas where they might be exposed to

contaminated airborne particulate material or vapors should have suitable

respiratory protection (Fechter 1995; McCullough 2000; OSHA 1998d),

with respirator ﬁt testing and training in the proper use and maintenance of

the respirator (OSHA 1998d; Sargent and Gallo 2003).

Medical Evaluation and Preventive Medicine for Personnel Development

and implementation of a program of medical evaluation and preventive

medicine should involve input from trained health professionals, such as

occupational health physicians and nurses. Conﬁdentiality and other medi-

cal and legal factors must be considered in the context of appropriate fed-

eral, state, and local regulations (e.g., PL 104-191).

A preemployment health evaluation and/or a health history evaluation

before work assignment is advisable to assess potential risks for individual

employees. Periodic medical evaluations are advisable for personnel in

speciﬁc risk categories. For example, personnel required to use respira-

tory protection may also require medical evaluation to ensure that they

are physically and psychologically able to use the respirator properly (Sar-

gent and Gallo 2003). An appropriate immunization schedule should be

adopted. It is important to immunize animal care personnel against tetanus

(NRC 1997), and preexposure immunization should be offered to people at

risk of infection or exposure to speciﬁc agents such as rabies virus (e.g., if

working with species at risk for infection) or hepatitis B virus (e.g., if work-

ing with human blood or human tissues, cell lines, or stocks). Vaccination

is recommended if research is to be conducted on infectious diseases for

which effective vaccines are available. More speciﬁc recommendations are

available in the BMBL (DHHS 2009). Preemployment or preexposure serum

collection is advisable only in speciﬁc circumstances as determined by an

occupational health and safety professional (NRC 1997). In such cases,

identiﬁcation, traceability, retention, and storage conditions of samples

should be considered, and the purpose for which the serum samples will be

used must be consistent with applicable federal and state laws.

Laboratory animal allergy has become a signiﬁcant issue for individuals

in contact with laboratory animals (Bush and Stave 2003; Gordon 2001;

Wolﬂe and Bush 2001; Wood 2001). The medical surveillance program

should promote the early diagnosis of allergies (Bush 2001; Bush and Stave

2003; Seward 2001) and include evaluation of an individual’s medical

history for preexisting allergies. Personnel training should include informa-

tion about laboratory animal allergies, preventive control measures, early

recognition and reporting of allergy symptoms, and proper techniques for

working with animals (Gordon et at. 1997; Schweitzer et al. 2003; Thulin

ANIMAL CARE AND USE PROGRAM 23

et al. 2002). PPE should be used to supplement, not replace, engineering

or process controls (Harrison 2001; Reeb-Whitaker et al. 1999). If PPE for

respiratory protection is necessary, appropriate ﬁt testing and training should

be provided.

Zoonosis surveillance should be a part of an OHSP (DHHS 2009; NRC

1997). Personnel should be instructed to notify their supervisors of potential

or known exposures and of suspected health hazards and illnesses. Non-

human primate diseases that are transmissible to humans can be serious haz-

ards (NRC 2003a). Animal technicians, veterinarians, investigators, students,

research technicians, maintenance workers, and others who have contact

with nonhuman primates or their tissues and body ﬂuids or who have duties

in nonhuman primate housing areas should be routinely screened for tuber-

culosis. Because of the potential for exposure to Macacine herpesvirus 1 (for-

merly Cercopithecine herpesvirus 1 or Herpes B virus), personnel who work

with or handle biologic samples (blood and tissues) from macaques should

have access to and be instructed in the use of bite and scratch emergency care

stations (Cohen et al. 2002). Injuries associated with macaques, their tissues

or body ﬂuids, or caging and equipment with which the animals have had

direct contact, should be carefully evaluated and appropriate postexposure

treatment and follow-up implemented (ibid.; NRC 2003a).

Clear procedures should be established for reporting all accidents, bites,

scratches, and allergic reactions (NRC 1997), and medical care for such

incidents should be readily available (Cohen et al. 2002; DHHS 2009).

Personnel Security

While contingency plans normally address natural disasters, they should

also take into account the threats that criminal activities such as personnel

harassment and assault, facility trespassing, arson, and vandalism pose

to laboratory animals, research personnel, equipment and facilities, and

biomedical research at the institution. Preventive measures should be con-

sidered, including preemployment screening and physical and information

technology security (Miller 2007).

Investigating and Reporting Animal Welfare Concerns

Safeguarding animal welfare is the responsibility of every individual

associated with the Program. The institution must develop methods for

reporting and investigating animal welfare concerns, and employees should

be aware of the importance of and mechanisms for reporting animal wel-

fare concerns. In the United States, responsibility for review and investi-

gation of these concerns rests with the IO and the IACUC. Response to

such reports should include communication of ﬁndings to the concerned

24 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

employee(s), unless such concerns are reported anonymously; corrective

actions if deemed necessary; and a report to the IO of the issue, ﬁndings,

and actions taken. Reported concerns and any corrective actions taken

should be documented.

Mechanisms for reporting concerns should be posted in prominent

locations in the facility and on applicable institutional website(s) with

instructions on how to report the concern and to whom. Multiple points

of contact, including senior management, the IO, IACUC Chair, and AV,

are recommended. The process should include a mechanism for anonym-

ity, compliance with applicable whistleblower policies, nondiscrimination

against the concerned/reporting party, and protection from reprisals.

Training and regular communication with employees (including person-

nel such as custodial, maintenance, and administrative staff, who are farther

removed from the animal use) about the institution’s animal use activities

may reduce potential concerns.

PROGRAM OVERSIGHT

The Role of the IACUC

IACUC Constitution and Function

The responsibility of the IACUC is to oversee and routinely evaluate the

Program. It is the institution’s responsibility to provide suitable orientation,

background materials, access to appropriate resources, and, if necessary,

speciﬁc training to assist IACUC members in understanding their roles and

responsibilities and evaluating issues brought before the committee.

Committee membership includes the following:

• a Doctor of Veterinary Medicine either certiﬁed (e.g., by ACLAM,

ECLAM, JCLAM, KCLAM) or with training and experience in labo-

ratory animal science and medicine or in the use of the species at

the institution

• at least one practicing scientist experienced in research involving

animals

• at least one member from a nonscientiﬁc background, drawn from

inside or outside the institution

• at least one public member to represent general community inter-

ests in the proper care and use of animals.

Public members should not be laboratory animal users, afﬁliated in

any way with the institution, or members of the immediate family of a per-

son who is afﬁliated with the institution. The public member may receive

ANIMAL CARE AND USE PROGRAM 25

compensation for participation and ancillary expenses (e.g., meals, park-

ing, travel), but the amount should be sufﬁciently modest that it does not

become a substantial source of income and thus risk compromising the

member’s association with the community and public at large.

For large institutions with many administrative units or departments,

no more than three voting members should be associated with a single

administrative unit (USDA 1985). The size of the institution and the nature

and extent of the Program will determine the number of members of the

committee and their terms of appointment. Institutions with broad research

programs may need to choose scientists from a number of disciplines and

experience to properly evaluate animal use protocols.

The committee is responsible for oversight and evaluation of the entire

Program and its components as described in other sections of the Guide.

Its oversight functions include review and approval of proposed animal

use (protocol review) and of proposed signiﬁcant changes to animal use;

regular inspection of facilities and animal use areas; regular review of the

Program; ongoing assessment of animal care and use; and establishment of

a mechanism for receipt and review of concerns involving the care and use

of animals at the institution. The committee must meet as often as neces-

sary to fulﬁll its responsibilities, and records of committee meetings and

results of deliberations should be maintained. Program review and facilities

inspections should occur at least annually or more often as required (e.g.,

by the Animal Welfare Act and PHS Policy). After review and inspection, a

written report (including any minority views) should be provided to the IO

about the status of the Program.

Protocol Review

The animal use protocol is a detailed description of the proposed use of

laboratory animals. The following topics should be considered in the prepa-

ration of the protocol by the researcher and its review by the IACUC:

• rationale and purpose of the proposed use of animals

• a clear and concise sequential description of the procedures involv-

ing the use of animals that is easily understood by all members of

the committee

• availability or appropriateness of the use of less invasive proce-

dures, other species, isolated organ preparation, cell or tissue cul-

ture, or computer simulation (see Appendix A, Alternatives)

• justiﬁcation of the species and number of animals proposed; when-

ever possible, the number of animals and experimental group sizes

should be statistically justiﬁed (e.g., provision of a power analysis;

see Appendix A, Experimental Design and Statistics)

26 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

• unnecessary duplication of experiments

• nonstandard housing and husbandry requirements

• impact of the proposed procedures on the animals’ well-being

• appropriate sedation, analgesia, and anesthesia (indices of pain or

invasiveness might aid in the preparation and review of protocols;

see Appendix A, Anesthesia, Pain, and Surgery)

• conduct of surgical procedures, including multiple operative

procedures

• postprocedural care and observation (e.g., inclusion of post-treat-

ment or postsurgical animal assessment forms)

• description and rationale for anticipated or selected endpoints

• criteria and process for timely intervention, removal of animals

from a study, or euthanasia if painful or stressful outcomes are

anticipated

• method of euthanasia or disposition of animals, including planning

for care of long-lived species after study completion

• adequacy of training and experience of personnel in the procedures

used, and roles and responsibilities of the personnel involved

• use of hazardous materials and provision of a safe working

environment.

While the responsibility for scientiﬁc merit review normally lies outside

the IACUC, the committee members should evaluate scientiﬁc elements

of the protocol as they relate to the welfare and use of the animals. For

example, hypothesis testing, sample size, group numbers, and adequacy

of controls can relate directly to the prevention of unnecessary animal

use or duplication of experiments. For some IACUC questions, input from

outside experts may be advisable or necessary. In the absence of evidence

of a formal scientiﬁc merit review, the IACUC may consider conducting

or requesting such a review (Mann and Prentice 2004). IACUC members

named in protocols or who have other conﬂicts must recuse themselves

from decisions concerning these protocols.

At times, protocols include procedures that have not been previously

encountered or that have the potential to cause pain or distress that cannot

be reliably predicted or controlled. Relevant objective information about

the procedures and the purpose of the study should be sought from the

literature, veterinarians, investigators, and others knowledgeable about the

effects on animals. If little is known about a speciﬁc procedure, limited

pilot studies, designed to assess both the procedure’s effects on the animals

and the skills of the research team and conducted under IACUC oversight,

are appropriate. General guidelines for protocol or method evaluation for

some of these situations are provided below, but they may not apply in all

instances.

ANIMAL CARE AND USE PROGRAM 27

Special Considerations for IACUC Review

Certain animal use protocols include procedures or approaches that

require special consideration during the IACUC review process due to their

potential for unrelieved pain or distress or other animal welfare concerns.

The topics below are some of the most common requiring special IACUC

consideration. For these and other areas the IACUC is obliged to weigh

the objectives of the study against potential animal welfare concerns. By

considering opportunities for reﬁnement, the use of appropriate nonanimal

alternatives, and the use of fewer animals, both the institution and the

principal investigator (PI) can begin to address their shared obligations for

humane animal care and use.

Experimental and Humane Endpoints The experimental endpoint of a study

occurs when the scientiﬁc aims and objectives have been reached. The

humane endpoint is the point at which pain or distress in an experimental

animal is prevented, terminated, or relieved. The use of humane endpoints

contributes to reﬁnement by providing an alternative to experimental end-

points that result in unrelieved or severe animal pain and distress, including

death. The humane endpoint should be relevant and reliable (Hendriksen

and Steen 2000; Olfert and Godson 2000; Sass 2000; Stokes 2002). For

many invasive experiments, the experimental and humane endpoints are

closely linked (Wallace 2000) and should be carefully considered during

IACUC protocol review. While all studies should employ endpoints that

are humane, studies that commonly require special consideration include

those that involve tumor models, infectious diseases, vaccine challenge,

pain modeling, trauma, production of monoclonal antibodies, assess-

ment of toxicologic effects, organ or system failure, and models of cardio-

vascular shock.

The PI, who has precise knowledge of both the objectives of the study

and the proposed model, should identify, explain, and include in the animal

use protocol a study endpoint that is both humane and scientiﬁcally sound.

The identiﬁcation of humane endpoints is often challenging, however,

because multiple factors must be weighed, including the model, species

(and sometimes strain or stock), animal health status, study objectives,

institutional policy, regulatory requirements, and occasionally conﬂicting

scientiﬁc literature. Determination of humane endpoints should involve the

PI, the veterinarian, and the IACUC, and should be deﬁned when possible

before the start of the study (Olfert and Godson 2000; Stokes 2000).

Information that is critical to the IACUC’s assessment of appropriate end-

point consideration in a protocol includes precise deﬁnition of the humane

endpoint (including assessment criteria), the frequency of animal observa-

tion, training of personnel responsible for assessment and recognition of the

28 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

humane endpoint, and the response required upon reaching the humane

endpoint. An understanding of preemptive euthanasia (Toth 2000), behavioral

or physiologic deﬁnitions of the moribund state (ibid.), and the use of study-

speciﬁc animal assessment records (Morton 2000; Paster et al. 2009) can

aid the PI and IACUC when considering or developing proposed endpoints.

When novel studies are proposed or information for an alternative endpoint

is lacking, the use of pilot studies is an effective method for identifying and

deﬁning humane endpoints and reaching consensus among the PI, IACUC,

and veterinarian. A system for communication with the IACUC should be

in place both during and after such studies. Numerous publications address

speciﬁc proposals for the application and use of humane endpoints (e.g.,

CCAC 1998; ILAR 2000; OECD 1999; Toth 1997; UKCCCR 1997).

Unexpected Outcomes Fundamental to scientiﬁc inquiry is the investiga-

tion of novel experimental variables. Because of the potential for unex-

pected outcomes that may affect animal well-being when highly novel

variables are introduced, more frequent monitoring of animals may be

required. With their inherent potential for unanticipated phenotypes, GMAs

are an example of models for which increased monitoring for unexpected

outcomes could be implemented (Dennis 1999).

GMAs, particularly mice and ﬁsh, are important animal models, and

new methods and combinations of genetic manipulation are constantly

being developed (Gondo 2008). Regardless of whether genetic manipula-

tion is targeted or random, the phenotype that initially results is often unpre-

dictable and may lead to expected or unexpected outcomes that affect the

animal’s well-being or survival at any stage of life. For example, in some

instances genetic modiﬁcation has led to unforeseen immunodeﬁciency,

requiring the GMA offspring to be held under specialized bioexclusion

conditions (Mumphrey et al. 2007); and the promoter sequences used to

direct expression of transgenes to speciﬁc tissues have varying degrees of

speciﬁcity (“leakiness”) that can lead to unanticipated phenotypes (Moore-

head et al. 2003). These examples illustrate the diversity of unanticipated

outcomes and emphasize the need for diligent monitoring and professional

judgment to ensure the animals’ well-being (Dennis 2000). The ﬁrst off-

spring of a newly generated GMA line should be carefully observed from

birth into early adulthood for signs of disease, pain, or distress. Investigators

may ﬁnd that the phenotype precludes breeding of particular genotypes or

that unexpected infertility occurs, situations that could lead to increases in

the numbers of animals used and revision of the animal use protocol. When

the initial characterization of a GMA reveals a condition that negatively

affects animal well-being, this should be reported to the IACUC, and more

extensive analysis may be required to better deﬁne the phenotype (Brown et

al. 2000; Crawley 1999; Dennis 2000). Such monitoring and reporting may

ANIMAL CARE AND USE PROGRAM 29

help to determine whether proactive measures can circumvent or alleviate

the impact of the genetic modiﬁcation on the animal’s well-being and to

establish humane endpoints speciﬁc to the GMA line.

Physical Restraint Physical restraint is the use of manual or mechanical

means to limit some or all of an animal’s normal movement for the purpose

of examination, collection of samples, drug administration, therapy, or

experimental manipulation. Animals are restrained for brief periods, usually

minutes, in many research applications.

Restraint devices should be suitable in size, design, and operation

to minimize discomfort, pain, distress, and the potential for injury to the

animal and the research staff. Dogs, nonhuman primates, and many other

animals can be trained, through use of positive reinforcement techniques,

to cooperate with research procedures or remain immobile for brief peri-

ods (Boissy et al. 2007; Laule et al. 2003; Meunier 2006; Prescott and

Buchanan-Smith 2003; Reinhardt 1991, 1995; Sauceda and Schmidt 2000;

Yeates and Main 2009).

Prolonged restraint, including chairing of nonhuman primates, should

be avoided unless it is essential for achieving research objectives and is

speciﬁcally approved by the IACUC (NRC 2003b). Systems that do not

limit an animal’s ability to make normal postural adjustments (e.g., sub-

cutaneous implantation of osmotic minipumps in rodents, backpack-ﬁtted

infusion pumps in dogs and nonhuman primates, and free-stall housing for

farm animals) should be used when compatible with protocol objectives.

Animals that do not adapt to necessary restraint systems should be removed

from the study. When restraint devices are used, they should be speciﬁcally

designed to accomplish research goals that are impossible or impractical to

accomplish by other means or to prevent injury to animals or personnel.

The following are important guidelines for restraint:

• Restraint devices should not be considered a normal method of

housing, and must be justiﬁed in the animal use protocol.

• Restraint devices should not be used simply as a convenience in

handling or managing animals.

• Alternatives to physical restraint should be considered.

• The period of restraint should be the minimum required to accom-

plish the research objectives.

• Animals to be placed in restraint devices should be given train-

ing (with positive reinforcement) to adapt to the equipment and

personnel.

• Animals that fail to adapt should be removed from the study.

• Provision should be made for observation of the animal at appropri-

ate intervals, as determined by the IACUC.

30 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

• Veterinary care must be provided if lesions or illnesses associated

with restraint are observed. The presence of lesions, illness, or

severe behavioral change often necessitates the temporary or per-

manent removal of the animal from restraint.

• The purpose of the restraint and its duration should be clearly

explained to personnel involved with the study.

Multiple Survival Surgical Procedures Surgical procedures in the laboratory

setting may be categorized as major or minor (USDA 1985). Whether a

procedure is major or minor should be evaluated on a case-by-case basis,

as determined by the veterinarian and IACUC (NRC 2003b; Silverman et al.

2007; for additional discussion see Chapter 4, Surgical Procedures).

Regardless of classiﬁcation, multiple surgical procedures on a single

animal should be evaluated to determine their impact on the animal’s well-

being. Multiple major surgical procedures on a single animal are accept-

able only if they are (1) included in and essential components of a single

research project or protocol, (2) scientiﬁcally justiﬁed by the investigator, or

(3) necessary for clinical reasons. Conservation of scarce animal resources

may justify the conduct of multiple major surgeries on a single animal,

but the application of such a practice on a single animal used in separate

protocols is discouraged and should be reviewed critically by the IACUC.

When applicable, the IO must submit a request to the USDA/APHIS and

receive approval in order to allow a regulated animal to undergo multiple

major survival surgical procedures in separate unrelated research protocols

(USDA 1985, 1997a). Justiﬁcations for allowing animals not regulated by

the USDA to undergo multiple survival procedures that meet the above

criteria should conform to those required for regulated species. If multiple

survival surgery is approved, the IACUC should pay particular attention to

animal well-being through continuing evaluation of outcomes. Cost sav-

ings alone is not an adequate reason for performing multiple major survival

surgical procedures.

Some procedures characterized as minor may induce substantial post-

procedural pain or impairment and should similarly be scientiﬁcally justi-

ﬁed if performed more than once in a single animal.

Food and Fluid Regulation Regulation of food or ﬂuid intake may be

required for the conduct of some physiological, neuroscience, and behav-

ioral research protocols. The regulation process may entail scheduled

access to food or ﬂuid sources, so an animal consumes as much as desired

at regular intervals, or restriction, in which the total volume of food or ﬂuid

consumed is strictly monitored and controlled (NRC 2003b). The objective

when these studies are being planned and executed should be to use the

ANIMAL CARE AND USE PROGRAM 31

least restriction necessary to achieve the scientiﬁc objective while maintain-

ing animal well-being.

The development of animal protocols that involve the use of food or

ﬂuid regulation requires the evaluation of three factors: the necessary level

of regulation, potential adverse consequences of regulation, and methods

for assessing the health and well-being of the animals (NRC 2003b). In addi-

tion, the following factors inﬂuence the amount of food or ﬂuid restriction

that can be safely used in a speciﬁc protocol: the species, strain, or stock,

gender, and age of the animals; thermoregulatory demand; type of housing;

time of feeding, nutritive value, and ﬁber content of the diet (Heiderstadt et

al. 2000; Rowland 2007); and prior experimental manipulation. The degree

of food or ﬂuid restriction necessary for consistent behavioral performance

is inﬂuenced by the difﬁculty of the task, the individual animal, the motiva-

tion required of the animal, and the effectiveness of animal training for a

speciﬁc protocol-related task.

The animals should be closely monitored to ensure that food and

ﬂuid intake meets their nutritional needs (Toth and Gardiner 2000). Body

weights should be recorded at least weekly and more often for animals

requiring greater restrictions (NRC 2003b). Written records should be main-

tained for each animal to document daily food and ﬂuid consumption,

hydration status, and any behavioral and clinical changes used as criteria

for temporary or permanent removal of an animal from a protocol (Morton

2000; NRC 2003b). In the case of conditioned-response research protocols,

use of a highly preferred food or ﬂuid as positive reinforcement, instead of

restriction, is recommended. Caloric restriction, as a husbandry technique

and means of weight control, is discussed in Chapter 3.

Use of Non-Pharmaceutical-Grade Chemicals and Other Substances The

use of pharmaceutical-grade chemicals and other substances ensures that

toxic or unwanted side effects are not introduced into studies conducted

with experimental animals. They should therefore be used, when available,

for all animal-related procedures (USDA 1997b). The use of non-pharma-

ceutical-grade chemicals or substances should be described and justiﬁed in

the animal use protocol and be approved by the IACUC (Wolff et al. 2003);

for example, the use of a non-pharmaceutical-grade chemical or substance

may be necessary to meet the scientiﬁc goals of a project or when a vet-

erinary or human pharmaceutical-grade product is unavailable. In such

instances, consideration should be given to the grade, purity, sterility, pH,

pyrogenicity, osmolality, stability, site and route of administration, formula-

tion, compatibility, and pharmacokinetics of the chemical or substance to

be administered, as well as animal welfare and scientiﬁc issues relating to

its use (NIH 2008).

32 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

Field Investigations Investigations may involve the observation or use of

nondomesticated vertebrate species under ﬁeld conditions. Many ﬁeld

investigations require international, federal, state, and/or local permits,

which may call for an evaluation of the scientiﬁc merit of the proposed

study and a determination of the potential impact on the population or

species to be studied.

Additionally, occupational health and safety issues, including zoo-

noses, should be reviewed by the institution’s health and safety commit-

tee or ofﬁce, with assurances to the IACUC that the ﬁeld study does not

compromise the health and safety of either animals or persons in the ﬁeld.

Principal investigators conducting ﬁeld research should be knowledgeable

about relevant zoonotic diseases, associated safety issues, and any laws or

regulations that apply. Exceptions to the above should be clearly deﬁned

and evaluated by the IACUC.

In preparing the design of a ﬁeld study, investigators are encouraged

to consult with relevant professional societies and available guidelines (see

Appendix A). Veterinary input may be needed for projects involving capture,

individual identiﬁcation, sedation, anesthesia, surgery, recovery, holding,

transportation, release, or euthanasia. Issues associated with these activities

are similar if not identical to those for species maintained and used in the

laboratory. When species are removed from the wild, the protocol should

include plans for either a return to their habitat or their ﬁnal disposition, as

appropriate.

The Guide does not purport to be a compendium of all information

regarding ﬁeld biology and methods used in wildlife investigations, but the

basic principles of humane care and use apply to animals living under natu-

ral conditions. IACUCs engaged in the review of ﬁeld studies are encour-

aged to consult with a qualiﬁed wildlife biologist.

Agricultural Animals The use of agricultural animals in research is sub-

ject to the same ethical considerations as for other animals in research,

although it is often categorized as either biomedical or agricultural because

of government regulations and policies, institutional policies, administra-

tive structure, funding sources, and/or user goals (Stricklin et al. 1990). This

categorization has led to a dual system with different criteria for evaluating

protocols and standards of housing and care for animals of the same species

on the basis of stated biomedical or agricultural research objectives (Strick-

lin and Mench 1994). With some studies, differences in research goals may

lead to a clear distinction between biomedical and agricultural research.

For example, animal models of human diseases, organ transplantation, and

major surgery are considered biomedical uses; and studies on food and ﬁber

production, such as feeding trials, are usually considered agricultural uses.

But when the distinction is unclear, as in the case of some nutrition and

ANIMAL CARE AND USE PROGRAM 33

disease studies, administrators, regulators, and IACUCs face a dilemma in

deciding how to handle such studies (Stricklin et al. 1990). Decisions on

categorizing research uses of agricultural animals and deﬁning standards

for their care and use should be made by the IACUC based on both the

researcher’s goals and concern for animal well-being. Regardless of the

category of research, institutions are expected to provide oversight of all

research animals and ensure that pain and distress are minimized.

The protocol, rather than the category of research, should determine the

setting (farm or laboratory). Housing systems for agricultural animals used in

biomedical research may or may not differ from those used in agricultural

research; animals used in either type of research can be housed in cages,

stalls, paddocks, or pastures (Tillman 1994). Some agricultural studies need

uniform conditions to minimize environmental variability, and some bio-

medical studies are conducted in farm settings. Agricultural research often

necessitates that animals be managed according to contemporary farm

production practices (Stricklin and Mench 1994), and natural environmen-

tal conditions might be desirable for agricultural research, whereas control

of environmental conditions to minimize variation might be desirable in

biomedical research (Tillman 1994).

The Guide applies to agricultural animals used in biomedical research,

including those maintained in typical farm settings. For animals maintained

in a farm setting, the Guide for the Care and Use of Agricultural Animals in

Research and Teaching (FASS 2010) is a useful resource. Information about

environmental enrichment, transport, and handling may be helpful in both

agricultural and biomedical research settings. Additional information about

facilities and management of farm animals in an agricultural setting is avail-

able from the Midwest Plan Service (1987) and from agricultural engineers

or animal science experts.

Postapproval Monitoring

Continuing IACUC oversight of animal activities is required by federal

laws, regulations, and policies. A variety of mechanisms can be used to

facilitate ongoing protocol assessment and regulatory compliance. Postap-

proval monitoring (PAM) is considered here in the broadest sense, consist-

ing of all types of protocol monitoring after the IACUC’s initial protocol

approval.

PAM helps ensure the well-being of the animals and may also provide

opportunities to reﬁne research procedures. Methods include continuing

protocol review; laboratory inspections (conducted either during regular

facilities inspections or separately); veterinary or IACUC observation of

selected procedures; observation of animals by animal care, veterinary, and

IACUC staff and members; and external regulatory inspections and assess-

34 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

ments. The IACUC, veterinary, animal care, and compliance staff may all

conduct PAM, which may also serve as an educational tool.

Continuing protocol review typically consists of an annual update or

review as well as the triennial review required by the PHS. The depth of

such reviews varies from a cursory update to a full committee review of the

entire protocol. Some institutions use the annual review as an opportunity

for the investigator to submit proposed amendments for future procedures,

to provide a description of any adverse or unanticipated events, and to pro-

vide updates on work progress. For the triennial review, many institutions

require a complete new protocol submission and may request a progress

report on the use of animals during the previous 3 years.

Both the Health Research Extension Act and the AWA require the

IACUC to inspect animal care and use facilities, including sites used for

animal surgeries, every 6 months. As part of a formal PAM program some

institutions combine inspection of animal study sites with concurrent review

of animal protocols. Based on risks to animals and their handlers, other

study areas may require more or less frequent inspections. Examples of

effective monitoring strategies include

• examination of surgical areas, including anesthetic equipment, use

of appropriate aseptic technique, and handling and use of con-

trolled substances

• review of protocol-related health and safety issues

• review of anesthetic and surgical records

• regular review of adverse or unexpected experimental outcomes

affecting the animals

• observation of laboratory practices and procedures and comparison

with approved protocols.

Institutions may also consider the use of veterinary staff and/or animal

health technicians to observe increased risk procedures for adverse events

(e.g., novel survival surgeries, pain studies, tumor growth studies) and report

their ﬁndings for review by the IACUC. The level of formality and intensity

of PAM should be tailored to institutional size and complexity, and in all

cases should support a culture of care focusing on the animals’ well-being

(Klein and Bayne 2007). Regardless of the methods used or who conducts

and coordinates the monitoring, PAM programs are more likely to succeed

when the institution encourages an educational partnership with investiga-

tors (Banks and Norton 2008; Collins 2008; Dale 2008; Lowman 2008;

Plante and James 2008; Van Sluyters 2008).

ANIMAL CARE AND USE PROGRAM 35

DISASTER PLANNING AND EMERGENCY PREPAREDNESS

Animal facilities may be subject to unexpected conditions that result in

the catastrophic failure of critical systems or signiﬁcant personnel absentee-

ism, or other unexpected events that severely compromise ongoing animal

care and well-being (ILAR 2010). Facilities must therefore have a disaster

plan. The plan should deﬁne the actions necessary to prevent animal pain,

distress, and deaths due to loss of systems such as those that control venti-

lation, cooling, heating, or provision of potable water. If possible the plan

should describe how the facility will preserve animals that are necessary

for critical research activities or are irreplaceable. Knowledge of the geo-

graphic locale may provide guidance as to the probability of a particular

type of disaster.

Disaster plans should be established in conjunction with the respon-

sible investigator(s), taking into consideration both the priorities for triaging

animal populations and the institutional needs and resources. Animals that

cannot be relocated or protected from the consequences of the disaster must

be humanely euthanized. The disaster plan should identify essential person-

nel who should be trained in advance in its implementation. Efforts should

be taken to ensure personnel safety and provide access to essential person-

nel during or immediately after a disaster. Such plans should be approved

by the institution and be part of the overall institutional disaster response

plan that is coordinated by the IO or another senior-level administrator. Law

enforcement and emergency personnel should be provided with a copy

of the plan for comment and integration into broader, areawide planning

(Vogelweid 1998).

REFERENCES

AAALAC [Association for Assessment and Accreditation of Laboratory Animal Care] Interna-

tional. 2003. Who’s responsible for offsite animals? Connection Spring:6-11, 13. Available

at www.aaalac.org/publications.

ACLAM [American College of Laboratory Animal Medicine]. 1996. Adequate Veterinary Care.

Available at www.aclam.org/education/guidelines/position_adequatecare.html; accessed

May 10, 2010.

Anderson LC. 2007. Institutional and IACUC responsibilities for animal care and use education

and training programs. ILAR J 48:90-95.

AVMA [American Veterinary Medical Association]. 2008. Introduction to Ergonomics Guide-

lines for Veterinary Practice. April. Available at www.avma.org/issues/policy/ergonomics.

asp; accessed May 10, 2010.

AVMA. 2010. Programs accredited by the AVMA Committee on Veterinary Technician Edu-

cation and Activities (CVTEA). Available at www.avma.org/education/cvea/vettech_

programs/vettech_programs.asp; accessed January 4, 2010.

Banks RE, Norton JN. 2008. A sample postapproval monitoring program in academia. ILAR J

49:402-418.

Bayne KA, Garnett NL. 2008. Mitigating risk, facilitating research. ILAR J 49:369-371.

36 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

Boissy A, Manteuffel G, Jensen MB, Moe RO, Spruijt B, Keeling L, Winckler C, Forkman B,

Dimitrov I, Langbein J, Bakken M, Veissier I, Aubert A. 2007. Assesment of positive emo-

tions in animals to improve their welfare. Physiol Behav 92:375-397.

Brown RE, Stanford L, Schellinck HM. 2000. Developing standardized behavioral tests for

knockout and mutant mice. ILAR J 41:163-174.

Bush RK. 2001. Assessment and treatment of laboratory animal allergy. ILAR J 42:55-64.

Bush RK, Stave GM. 2003. Laboratory animal allergy: An update. ILAR J 44:28-51.

CCAC [Canadian Council on Animal Care]. 1993. Guide to the Care and Use of Experimental

Animals, vol 1, 2nd ed. Olfert ED, Cross BM, McWilliam AA, eds. Ontario: CCAC.

CCAC. 1998. Guidelines on Choosing an Appropriate Endpoint in Experiments Using Animals

for Research, Teaching and Testing. Ottawa. Available at www.ccac.ca/en/CCAC_Pro-

grams/Guidelines_Policies/gdlines/endpts/appopen.htm; accessed May 10, 2010.

CDC [Centers for Disease Control and Prevention] and NIH [National Institutes of Health].

2000. Primary Containment for Biohazards: Selection, Installation and Use of Biological

Safety Cabinets, 2nd ed. Washington: Government Printing Ofﬁce. Available at www.cdc.

gov/od/ohs/biosfty/bsc/bsc.htm; accessed May 25, 2010.

CFR [Code of Federal Regulations]. 1984a. Title 10, Part 20. Standards for Protection against

Radiation. Washington: Ofﬁce of the Federal Register.

CFR. 1984b. Title 29, Part 1910, Occupational Safety and Health Standards, Subpart G, Oc-

cupational Health and Environmental Control, and Subpart Z, Toxic and Hazardous

Substances. Washington: Ofﬁce of the Federal Register.

CFR. 1984c. Title 29, Part 1910. Occupational Safety and Health Standards; Subpart I, Personal

Protective Equipment. Washington: Ofﬁce of the Federal Register.

CFR. 1998. Title 29, Section 1910.120. Inspection Procedures for the Hazardous Waste Opera-

tions and Emergency Response Standard. Washington: Ofﬁce of the Federal Register.

April 24.

CFR. 2002a. Title 42, Part 73. Possession, Use and Transfer of Select Agents and Toxins. Wash-

ington: Ofﬁce of the Federal Register. December 13.

CFR. 2002b. Title 7, Part 331; and Title 9, Part 121. Agricultural Bioterrorism Protection Act

of 2002: Possession, Use and Transfer of Select Agents and Toxins. Washington: Ofﬁce of

the Federal Register. December 13.

Cohen JI, Davenport DS, Stewart JA, Deitchmann S, Hilliard JK, Chapman LE, B Virus Working

Group. 2002. Recommendations for prevention of and therapy for exposure to B virus

(Cercopithecine herpesvirus 1). Clin Infect Dis 35:1191-1203.

Colby LA, Turner PV, Vasbinder MA. 2007. Training strategies for laboratory animal veterinar-

ians: Challenges and opportunities. ILAR J 48:143-155.

Collins JG. 2008. Postapproval monitoring and the IACUC. ILAR J 49:388-392.

Conarello SL, Shepard MJ. 2007. Training strategies for research investigators and technicians.

ILAR J 48:120-130.

Crawley JN. 1999. Behavioral phenotyping of transgenic and knockout mice: Experimental

design and evaluation of general health, sensory functions, motor abilities, and speciﬁc

behavioral tests. Brain Res 835:18-26.

Dale WE. 2008. Postapproval monitoring and the role of the compliance ofﬁce. ILAR J

49:393-401.

Dennis MB. 1999. Institutional animal care and use committee review of genetic engineering.

In: Gonder JC, Prentice ED, Russow L-M, eds. Genetic Engineering and Animal Welfare:

Preparing for the 21st Century. Greenbelt MD: Scientists Center for Animal Welfare.

Dennis MB. 2000. Humane endpoints for genetically engineered animal models. ILAR J

41:94-98.

ANIMAL CARE AND USE PROGRAM 37

DHHS [Department of Health and Human Services]. 2009. Biosafety in Microbiological and

Biomedical Laboratories, 5th ed. Chosewood LC, Wilson DE, eds. Washington: Gover-

nment Printing Ofﬁce. Available atAvailable at http://www.cdc.gov/biosafety/publications/bmbl5/

index.htm; accessed July 30, 2010.

FASS [Federation of Animal Science Societies]. 2010. Guide for the Care and Use of Agricul-

tural Animals in Research and Teaching, 3rd ed. Champlain, IL: FASS.

Fechter LD. 1995. Combined effects of noise and chemicals. Occup Med 10:609-621.

Foshay WR, Tinkey PT. 2007. Evaluating the effectiveness of training strategies: Performance

goals and testing. ILAR J 48:156-162.

Frasier D, Talka J. 2005. Facility design considerations for select agent animal research. ILAR

J 46:23-33.

Gonder JC. 2002. Regulatory compliance. In: Suckow MA, Douglas FA, Weichbrod RH, eds.

Management of Laboratory Animal Care and Use Programs. Boca Raton, FL: CRC Press.

p 163-185.

Gondo Y. 2008. Trends in large-scale mouse mutagenesis: From genetics to functional genom-

ics. Nat Rev Genet 9:803-810.

Gordon S. 2001. Laboratory animal allergy: A British perspective on a global problem. ILAR

J 42:37-46.

Gordon S, Wallace J, Cook A, Tee RD, Newman Taylor AJ. 1997. Reduction of exposure to

laboratory animal allergens in the workplace. Clin Exp Allergy 27:744-751.

Greene ME, Pitts ME, James ML. 2007. Training strategies for institutional animal care and use

committee (IACUC) members and the institutional ofﬁcial (IO). ILAR J 48:131-142.

Harrison DJ. 2001. Controlling exposure to laboratory animal allergens. ILAR J 42:17-36.

Heiderstadt KM, McLaughlin RM, Wright DC, Walker SE, Gomez-Sanchez CE. 2000. The effect

of chronic food and water restriction on open-ﬁeld behaviour and serum corticosterone

levels in rats. Lab Anim 34:20-28.

Hendriksen CFM, Steen B. 2000. Reﬁnement of vaccine potency testing with the use of hu-

mane endpoints. ILAR J 41:105-113.

Huerkamp MJ, Gladle MA, Mottet MP, Forde K. 2009. Ergonomic considerations and allergenErgonomic considerations and allergen

management. In: Hessler JR, Lerner NMD, eds. Planning and Designing Research Animal

Facilities. San Diego: Elsevier. p 115-128.

ILAR [Institute for Laboratory Animal Research, National Research Council]. 2000. Humane

Endpoints for Animals Used in Biomedical Research and Testing. ILAR J 41:59-123.

ILAR. 2010. Disaster planning and management. ILAR J 51:101-192.

IRAC [Interagency Research Animal Committee]. 1985. US Government Principles for Utili-

zation and Care of Vertebrate Animals Used in Testing, Research, and Training. Federal

at http://oacu.od.nih.gov/regs/USGovtPrncpl.htm; accessed May 10, 2010.

Klein HJ, Bayne KA. 2007. Establishing a culture of care, conscience, and responsibility:

Addressing the improvement of scientiﬁc discovery and animal welfare through science-

based performance standards. ILAR J 48:3-11.

Kreger MD. 1995. Training Materials for Animal Facility Personnel: AWIC Quick Bibliography

Series, 95-08. Beltsville MD: National Agricultural Library.

Lassnig C, Kolb A, Strobl B, Enjuanes L, Müller M. 2005. Studying human pathogens in human

models: Fine tuning the humanized mouse. Transgenic Res 14:803-806.

Laule GE, Bloomsmith MA, Schapiro SJ. 2003. The use of positive reinforcement training

techniques to enhance the care, management, and welfare of primates in the laboratory.

J Appl Anim Welf Sci 6:163-173.

Lowman RP. 2008. The institutional ofﬁcial and postapproval monitoring: The view from

10,000 feet. ILAR J 49:379-387.

38 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

Mann MD, Prentice ED. 2004. Should IACUCs review scientiﬁc merit of animal research

projects? Lab Anim (NY) 33:26-31.

McCullough NV. 2000. Personal respiratory protection. In: Fleming DO, Hunt DL, eds. Biologi-

cal Safety Principles and Practices. Washington: ASM Press. p 383-404.

Meunier LD. 2006. Selection, acclimation, training and preparation of dogs for the research

setting. ILAR J 47:326-347.

Midwest Plan Service. 1987. Structures and Environment Handbook, 11th ed. rev. Ames: Mid-

west Plan Service, Iowa State University.

Miller G. 2007. Science and the public: Animal extremists get personal. Science

318:1856-1858.

Moorehead RA, Sanchez OH, Baldwin RM, Khokha R. 2003. Transgenic overexpression of

IGF-II induces spontaneous lung tumors: A model for human lung adenocarcinoma.

Oncogene 22:853-857.

Morton DB. 2000. A systematic approach for establishing humane endpoints. ILAR J 41:80-86.

Morton WR, Knitter GH, Smith PV, Susor TG, Schmitt K. 1987. Alternatives to chronic restraint

of nonhuman primates. JAVMA 191:1282-1286.

Mumphrey SM, Changotra H, Moore TN, Heimann-Nichols ER, Wobus CE, Reilly MJ, Mogha-

damfalahi M, Shukla D, Karst SM. 2007. Murine norovirus 1 infection is associated with

histopathological changes in immunocompetent hosts, but clinical disease is prevented

by STAT1-dependent interferon responses. J Virol 81:3251-3263.

Newcomer CE. 2002. Hazard identiﬁcation and control. In: Suckow MA, Douglas FA, Weich-

brod RH, eds. Management of Laboratory Animal Care and Use Programs. Boca Raton,

FL: CRC Press. p 291-324.

NIH [National Institutes of Health]. 2002. Guidelines for Research Involving Recombinant

DNA Molecules. April. Available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html;

accessed May 20, 2010.

NIH. 2008. Guidelines for the Use of Non-Pharmaceutical-Grade Chemicals/Compounds in

Laboratory Animals. Animal Research Advisory Committee, Ofﬁce of Animal Care and

Use, NIH. Available at http://oacu.od.nih.gov/ARAC/documents/Pharmaceutical_Com-

pounds.pdf; accessed May 20, 2010.

NIOSH [National Institute for Occupational Safety and Health]. 1997a. Elements of Ergonom-

ics Programs: A Primer Based on Workplace Evaluations of Musculoskeletal Disorders

(NIOSH Publication No. 97-117). Cincinnati: NIOSH. p 16-24.

NIOSH. 1997b. Musculoskeletal Disorders and Workplace Factors: A Critical Review of Epi-

demiologic Evidence for Work-Related Musculoskeletal Disorders of the Neck, Upper Ex-

tremity, and Low Back. Bernard B, ed. Cincinnati: DHHS, PHS, CDDC, NIOSH. p 1-12.

NRC [National Research Council]. 1991. Education and Training in the Care and Use of Labo-

ratory Animals: A Guide for Developing Institutional Programs. Washington: National

Academy Press.

NRC. 1997. Occupational Health and Safety in the Care and Use of Research Animals. Wash-

ington: National Academy Press.

NRC. 2003a. Occupational Health and Safety in the Care and Use of Nonhuman Primates.

Washington: National Academies Press.

NRC. 2003b. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral

Research. Washington: National Academies Press.

NRC. 2004. Biotechnology Research in an Age of Terrorism. Washington: National Academies

Press.

OECD [Organisation for Economic Co-operation and Development]. 1999. Guidance Docu-

ment on Humane Endpoints for Experimental Animals Used in Safety Evaluation Studies.

Paris: OECD.

ANIMAL CARE AND USE PROGRAM 39

Olfert ED, Godson DL. 2000. Humane endpoints for infectious disease animal models. ILAR

J 41:99-104.

OSHA [Occupational Safety and Health Administration]. 1998a. Occupational Safety and

Health Standards. Subpart G, Occupational Health and Environmental Controls (29 CFR

1910). Washington: Department of Labor.

OSHA. 1998b. Occupational Safety and Health Standards. Subpart Z, Toxic and Hazardous Sub-

stances, Bloodborne Pathogens (29 CFR 1910.1030). Washington: Department of Labor.

OSHA. 1998c. Occupational Safety and Health Standards. Subpart G, Occupational Health

and Environmental Controls, Occupational Noise Exposure (29 CFR 1910.95). Washing-

ton: Department of Labor.

OSHA. 1998d. Occupational Safety and Health Standards. Subpart I, Personal Protective Equip-

ment, Respiratory Protection (29 CFR 1910.134). Washington: Department of Labor.

Paster EV, Villines KA, Hickman DL. 2009. Endpoints for mouse abdominal tumor models:

Reﬁnement of current criteria. Comp Med 59:234-241.

PHS [Public Health Service]. 2002. Public Health Service Policy on Humane Care and Use

of Laboratory Animals. Department of Health and Human Services, National Institutes

of Health, Ofﬁce of Laboratory Animal Welfare. Available at http://grants.nih.gov/grants/

olaw/references/phspol.htm; accessed January 14, 2010.

PL [Public Law] 104-191. 1996. Health Insurance Portability and Accountability Act (HIPAA)

of 1996. Washington: Government Printing Ofﬁce.

PL 107-56. 2001. Uniting and Strengthening America by Providing Appropriate Tools Required

to Intercept and Obstruct Terrorism (USA PATRIOT) Act of 2001. Washington: Govern-

ment Printing Ofﬁce. October 26.

PL 107-188. 2002. Public Health Security and Bioterrorism Preparedness and Response Act of

2002. Washington: Government Printing Ofﬁce. June 12.

Plante A, James ML. 2008. Program oversight enhancements (POE): The big PAM. ILAR J

49:419-425.

Prescott MJ, Buchanan-Smith HM. 2003. Training nonhuman primates using positive reinforce-

ment techniques. J Appl Anim Welf Sci 6:157-161.

Pritt S, Duffee N. 2007. Training strategies for animal care technicians and veterinary technical

staff. ILAR J 48:109-119.

Reeb-Whitaker CK, Harrison, DJ, Jones RB, Kacergis JB, Myers DD, Paigen B. 1999. Control

strategies for aeroallergens in an animal facility. J Allergy Clin Immunol 103:139-146.

Reinhardt V. 1991. Training adult male rhesus monkeys to actively cooperate during in-

homecage venipuncture. Anim Technol 42:11-17.

Reinhardt V. 1995. Restraint methods of laboratory non-human primates: A critical review.

Anim Welf 4:221-238.

Richmond JY, Hill RH, Weyant RS, Nesby-O’Dell SL, Vinson PE. 2003. What’s hot in animal

biosafety? ILAR J 44:20-27.

Rowland NE. 2007. Food or ﬂuid restriction in common laboratory animals: Balancing welfare

considerations with scientiﬁc inquiry. Comp Med 57:149-160.

Sargent EV, Gallo F. 2003. Use of personal protective equipment for respiratory protection.

ILAR J 44:52-56.

Sass N. 2000. Humane endpoints and acute toxicity testing. ILAR J 41:114-123.ILAR J 41:114-123.

Sauceda R, Schmidt MG. 2000. Reﬁning macaque handling and restraint techniques. LabReﬁning macaque handling and restraint techniques. Lab

Anim 29:47-49.

Schweitzer IB, Smith E, Harrison DJ, Myers DD, Eggleston PA, Stockwell JD, Paigen B, Smith

AL. 2003. Reducing exposure to laboratory animal allergens. Comp Med 53:487-492.

Seward JP. 2001. Medical surveillance of allergy in laboratory animal handlers. ILAR J 42:47-54.

Silverman J, Sukow MA, Murthy S, eds. 2007. The IACUC Handbook, 2nd ed. Boca Raton,

FL: CRC Press.

40 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS

Stokes WS. 2000. Reducing unrelieved pain and distress in laboratory animals using humane

endpoints. ILAR J 41:59-61.

Stokes WS. 2002. Humane endpoints for laboratory animals used in regulatory testing. ILAR

J 43:S31-S38.

Stricklin WR, Mench JA. 1994. Oversight of the use of agricultural animals in university teach-

ing and research. ILAR News 36:9-14.

Stricklin WR, Purcell D, Mench JA. 1990. Farm animals in agricultural and biomedical re-

search. In: The Well-Being of Agricultural Animals in Biomedical and Agricultural Re-

search: Proceedings from a SCAW-Sponsored Conference, September 6-7. Washington:

Scientists Center for Animal Welfare. p 1-4.

Thomann WR. 2003. Chemical safety in animal care, use, and research. ILAR J 44:13-19.

Thulin H, Bjorkdahl M, Karlsson AS, Renstrom A. 2002. Reduction of exposure to laboratory

animal allergens in a research laboratory. Ann Occup Hyg 46:61-68.

Tillman P. 1994. Integrating agricultural and biomedical research policies: Conﬂicts and op-

portunities. ILAR News 36:29-35.

Toth LA. 1997. The moribund state as an experimental endpoint. Contemp Top Lab Anim Sci

36:44-48.

Toth LA. 2000. Deﬁning the moribund condition as an experimental endpoint for animal

research. ILAR J 41:72-79.

Toth LA, Gardiner TW. 2000. Food and water restriction protocols: Physiological and behav-

ioral considerations. Contemp Top Lab Anim Sci 39:9-17.

UKCCCR [United Kingdom Coordinating Committee on Cancer Research]. 1997. Guidelines

for the Welfare of Animals in Experimental Neoplasia, 2nd ed. London: UKCCCR.

USC [United States Code]. Title 42, Chapter 6a, Subchapter III, Part H, Section 289d: Animals

in Research. Available at http://uscode.house.gov/download/pls/42CGA.txt.

USDA [US Department of Agriculture]. 1985. 9 CFR 1A. (Title 9, Chapter 1, Subchapter A):

Animal Welfare. Available at http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?sid=8314313bd

7adf2c9f1964e2d82a88d92andc=ecfrandtpl=/ecfrbrowse/Title09/9cfrv1_02.tpl; accessed

January 14, 2010.

USDA. 1997a. APHIS Policy #14, “Multiple Survival Surgery: Single vs. Multiple Procedures”

(April 14). Available at www.aphis.usda.gov/animal_welfare/downloads/policy/policy14.

pdf; accessed January 4, 2010.

USDA. 1997b. APHIS Policy #3, “Veterinary Care” (July 17). Available at www.aphis.usda.

gov/animal_welfare/downloads/policy/policy3.pdf; accessed January 9, 2010.

USDA. 2002. Facilities Design Standards. Manual 242.1. Available at www.afm.ars.usda.

gov/ppweb/PDF/242-01M.pdf; accessed May 10, 2010.

Van Sluyters RC. 2008. A guide to risk assessment in animal care and use programs: The meta-

phor of the 3-legged stool. ILAR J 49:372-378.

Yeates JW, Main DCJ. 2009. Assesment of positive welfare: A review. Vet Rev 175:293-300.

Vogelweid CM. 1998. Developing emergency management plans for university laboratory

animal programs and facilities. Contemp Top Lab Anim Sci 37:52-56.

Wallace J. 2000. Humane endpoints and cancer research. ILAR J 41:87-93.

Wolff A, Garnett N, Potkay S, Wigglesworth C, Doyle D, Thornton, D. 2003. Frequently asked

questions about the Public Health Service Policy on Humane Care and Use of Laboratory

Animals. Lab Anim 32(9):33-36.

Wolﬂe TL, Bush RK. 2001. The science and pervasiveness of laboratory animal allergy. ILAR

J 42:1-3.

Wood RA. 2001. Laboratory animal allergens. ILAR J 42:12-16.

Environment, Housing,

and Management

his chapter provides guidelines for the environment, housing, and

management of laboratory animals used or produced for research,

testing, and teaching. These guidelines are applicable across species

and are relatively general; additional information should be sought about

how to apply them to meet the speciﬁc needs of any species, strain, or use

(see Appendix A for references). The chapter is divided into recommenda-

tions for terrestrial (page 42) and aquatic animals (page 77), as there are

fundamental differences in their environmental requirements as well as ani-

mal husbandry, housing, and care needs. Although formulated speciﬁcally

for vertebrate species, the general principles of humane animal care as set

out in the Guide may also apply to invertebrate species.

The design of animal facilities combined with appropriate animal hous-

ing and management are essential contributors to animal well-being, the

quality of animal research and production, teaching or testing programs

involving animals, and the health and safety of personnel. An appropriate

Program (see Chapter 2) provides environments, housing, and manage-

ment that are well suited for the species or strains