2nd Edition 

2002 

Institutional Animal 

Care and Use 

Committee Guidebook 
2nd Edition 

2002 

Institutional Animal 

Care and Use 

Committee Guidebook 

This Guidebook is provided for informational purposes only. 

It neither establishes nor reflects a change in PHS Policy on 

Humane Care and Use of Laboratory Animals. 
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Table of Contents 

Foreword ..................................................................................................... v


Editorial Board ...........................................................................................vii


Contributing Authors ................................................................................. viii


Office of Laboratory Animal Welfare (OLAW) .............................................. x


Abbreviations and Acronyms ..................................................................... xi


Sections 

A. The IACUC .......................................................................................... 1


A.1. Timeline, Background and History .......................................... 3


A.2. Authority, Composition and Functions .................................. 11


A.3. Operation and Administration................................................ 19


A.4. Training for Members ............................................................. 27


A.5. Legal Concerns ..................................................................... 31


B. Oversight of the Animal Care and Use Program ....................... 35


B.1. Program and Facility Review ................................................. 37


B.2. Animal Environment, Housing and Management .................. 43


B.2.a. General ...................................................................... 43


B.2.b. Animal Environment ................................................... 44


B.2.c. Husbandry ................................................................. 45


B.2.d. Facility Maintenance .................................................. 48


B.2.e. Emergency, Weekend and Holiday Care ................... 49


B.2.f. Behavioral Management for Laboratory Animals ...... 49


B.3. Role of the Veterinarian ......................................................... 53


B.4. Occupational Health and Safety ............................................ 59


B.5. Personnel Training and Education ......................................... 65


B.6. Emergency Preparedness ..................................................... 71


B.6.a. Security and Crisis Management............................... 71


B.6.b. Disaster Planning ....................................................... 74


i 
ii Table of Contents 

C. Review of Proposals ....................................................................... 83


C.1. Fundamental Issues .............................................................. 85


C.2. Protocol Review Criteria ........................................................ 97


C.2.a. Alternatives – Replacement, Reduction


and Refinement ......................................................... 97


C.2.b. Euthanasia ............................................................... 101


C.2.c. Humane Endpoints .................................................. 103


C.2.d. Minimization of Pain and Distress ........................... 109


C.2.e. Personnel Qualifications .......................................... 114


C.2.f. Veterinary Review and Consultation ........................ 117


C.3. Other Protocol Review Considerations ............................... 121


C.3.a. Agricultural Research............................................... 121


C.3.b. Antibody Production ................................................ 125


C.3.c. Breeding Colonies ................................................... 130


C.3.d. Field Studies ............................................................ 134


C.3.e. Hazardous Materials ................................................ 138


C.3.f. Instructional Use of Animals .................................... 142


C.3.g. Surgery .................................................................... 145


C.3.h. Transgenic Animals .................................................. 148


C.4. Monitoring of Approved Protocols ...................................... 153


D. Evaluation of Animal Care and Use Concerns ......................... 157


E. Recordkeeping and Communications ....................................... 167


E.1. Recordkeeping and Reporting ............................................ 169


E.2. Communications ................................................................. 179


Appendices ........................................................................................... 181


Appendix A. Resources ................................................................ 183


Appendix B.	 Office of Laboratory Animal Welfare


Organizational Chart ................................................ 191


Appendix C.	 Mandatory IACUC Issues Identified


During AAALAC International Site Visits .................. 193

Table of Contents iii 

Appendix D.	 Recommendations of the 2000 AVMA


Panel on Euthanasia ................................................ 195


Appendix E.	 Federal and State Permits Required


for Field Studies ....................................................... 199


Appendix F.	 U.S. Government Principles for the Utilization


and Care of Vertebrate Animals Used in


Testing, Research and Training ................................ 209


List of Tables by Section 

A.2. Table A.	 Comparison of IACUC


Membership Requirements .................................... 14


A.2. Table B. Federally Mandated Functions of the IACUC......... 17


B.5. Table A. General Training Objectives.................................... 68


B.6. Table A. Examples of Categories of Emergencies ............... 79


B.6. Table B. Core Functions of an Animal Facility ...................... 80


C.1. Table A.	 Regulatory Criteria Applicable to Protocol


Review as Defined in PHS Policy and


USDA Regulations .................................................. 86


C.2.a. Table A. Methods for Reduction of Numbers


of Animals Used ..................................................... 98


C.2.c. Table A. Examples of Humane Endpoints for Studies


with Potential Lethality ......................................... 107


C.2.d. Table A. Definitions of Terminology Related to


Pain and Distress.................................................. 112


C.2.d. Table B. Signs of Acute Pain .............................................. 112


C.2.d. Table C. Signs, Degree and Length of Surgically


Produced Pain ...................................................... 113


E.1. Table A. Federal Requirements: Recordkeeping ................ 174


E.1. Table B.	 Federal Requirements: Assurance


and Registration ................................................... 175


E.1. Table C.	 Federal Requirements: Report of


Semiannual Evaluations ....................................... 176


E.1. Table D. Federal Requirements: Annual Report ................. 177


E.1. Table E.	 Federal Requirements: Suspensions


and Noncompliance ............................................. 178

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Foreword 

The original OPRR/ARENA IACUC Guidebook was published in 1992 and 

has served as a useful resource to the animal research community. This 

revised edition, the ARENA/OLAW IACUC Guidebook, continues to support the fundamental principle on which the animal care and use program 

is based: self-regulation with oversight. It clearly demonstrates the increased 

role of the Institutional Animal Care and Use Committee (IACUC) in ensuring 

the ethical and sensitive care and use of animals in research, teaching 

and testing. 

This Guidebook is the product of an ARENA-established editorial board of 

knowledgeable individuals who have IACUC experience and are familiar with 

the evolution of IACUC issues and relevant documents published during the 

past decade. Sections from the original document have been updated, and 

new sections added to incorporate state of the art knowledge regarding the 

functioning of IACUCs and institutional animal care and use programs. This 

Guidebook does not create new or different interpretations of the PHS Policy 

on Humane Care and Use of Laboratory Animals, legislation, or USDA animal 

welfare regulations. 

The most current knowledge and understandings were sought through distinguished authors with experience and expertise. New references, resources 

and contemporary scientific and “road tested” guidance have been incorporated. For example, the emphasis of the 1996 edition of the Guide for the 

Care and Use of Laboratory Animals on performance goals as opposed to 

engineering approaches is a theme that resonates throughout. Other new 

reports, such as the 1997 Occupational Health and Safety in the Care and 

Use of Research Animals and the 1998 The Psychological Well-Being of 

Nonhuman Primates, both published by the National Research Council have 

offered new insights and approaches that are reflected herein. The AVMA 

Panel on Euthanasia also published new guidelines in 2001. 

Additional knowledge and changing trends in research have mandated broader 

and deeper coverage of topics in this Guidebook. New topic areas include 

training IACUC members, disaster planning, managing breeding colonies, 

and the use of transgenic animals. New federal requirements and directives 

v 
vi Foreword 

have been incorporated, and feedback from the field during the past ten 

years has resulted in emphasis on topics such as the role of the nonaffiliated 

member, the application of the three R’s (reduction, refinement and replacement) of alternatives, and the development of humane endpoints. 

It is with a great sense of gratitude and respect for my colleagues who served 

on the editorial board and to the 30 authors who generously shared their time 

and expertise that I submit this document to the Office of Laboratory Animal 

Welfare. I would especially like to express my appreciation to the Project 

Director, Carol Wigglesworth, and her colleagues in NIH’s OLAW who gave 

untold hours of editing and guidance to make this project not only possible, 

but also enjoyable. ARENA also gratefully acknowledges the technical 

review for consistency with the provisions of the USDA animal welfare regulations provided by Dr. Ron DeHaven, Deputy Administrator, Animal Care, 

APHIS, and his headquarters staff. This has truly been a labor of love 

by many dedicated individuals in the animal research community and I 

feel honored to have been a part of this effort. 

Marky Pitts 

Chair, Editorial Board 
vii 

Editorial Board 

Marky Pitts, Chair 

Director, Animal Subjects Program 

University of California–San Diego 

La Jolla, CA 

Kathryn Bayne, M.S., Ph.D., D.V.M. 

Co-Chair


Associate Director


AAALAC International


Rockville, MD


Lynn C. Anderson, D.V.M. 

Senior Director


Comparative Medicine


MERCK Research Laboratories


Rahway, NJ


David B. Bernhardt 

Institutional Animal Care 

and Use Committee 

Albert Einstein Healthcare Network 

Philadelphia, PA 

Molly Greene 

Director


Office of Academic Support


University of Texas Health Science


Center–San Antonio


San Antonio, TX


Harry Klemfuss, Ph.D. 

Associate Director


Animal Subjects Program


University of California–San Diego


La Jolla, CA


Gwenn S.F. Oki, M.P.H. 

Director


Research Subjects Protection


City of Hope/Beckman


Research Institute


Duarte, CA


Harry Rozmiarek, D.V.M., Ph.D. 

Professor and Chief 

Laboratory Animal Medicine 

University Veterinarian 

University of Pennsylvania 

Philadelphia, PA 

Peter Theran, V.M.D. 

Vice President


Division of Health and Hospitals


Massachusetts Society for


the Prevention of Cruelty


to Animals, AHES


Boston, MA


Richard C. Van Sluyters, O.D., Ph.D. 

Professor, School of Optometry


Chair, Animal Care and


Use Committee


Faculty Assistant to the Vice


Chancellor for Research


University of California–Berkeley


Berkeley, CA


OLAW Project Director 

Carol Wigglesworth 

Senior Policy Analyst


Office of Laboratory Animal Welfare


National Institutes of Health


Bethesda, MD


Editorial Consultant 

Liz McDonald 

Corporate Communications 

San Diego, CA 
viii Contributing Authors 

Contributing Authors 

Lynn C. Anderson, D.V.M. 

Senior Director


Comparative Medicine


MERCK Research Laboratories


Rahway, NJ


Michael B. Ballinger, D.V.M. 

Director


Comparative Medicine


Abbott laboratories


Abbott Park, IL


Kathryn Bayne, M.S., Ph.D., D.V.M. 

Associate Director 

AAALAC International 

Rockville, MD 

B. Taylor Bennett, D.V.M., Ph.D. 

Associate Vice Chancellor


for Research


University of Illinois–Chicago


Chicago, IL


David B. Bernhardt 

Institutional Animal Care 

and Use Committee 

Albert Einstein Healthcare Network 

Philadelphia, PA 

Marilyn J. Brown, D.V.M., M.S. 

Director


Animal Care & Use Program


Dartmouth College


Lebanon, NH


Terrie Cunliffe-Beamer, D.V.M., M.S. 

Head, Clinical Laboratory


Animal Medicine


The Jackson Laboratory


Bar Harbor, ME


Nicole Duffee, D.V.M., Ph.D. 

Division of Comparative Medicine


Washington University


School of Medicine


St. Louis, MO


James Fox, M.S., D.V.M. 

Division of Comparative Medicine


Massachusetts Institute


of Technology


Cambridge, MA


Lauretta W. Gerrity, D.V.M. 

Director


Animal Resources Program


University of Alabama–Birmingham


Birmingham, AL


Molly Greene 

Director


Office of Academic Support


University of Texas


Health Science Center–San Antonio


San Antonio, TX


J. R. Haywood, Ph.D. 

Professor


Department of Pharmacology


University of Texas Health


Science Center–San Antonio


San Antonio, TX


Harry Klemfuss, Ph.D. 

Associate Director


Animal Subjects Program


University of California–San Diego


La Jolla, CA


Joy A. Mench, Ph.D. 

Director, Center for Animal Welfare 

University of California–Davis 

Davis, CA 
Contributing Authors ix 

Christian E. Newcomer, V.M.D., M.S. 

Director


Laboratory Animal Medicine


University of North Carolina


Chapel Hill, NC


Gwenn S.F. Oki, M.P.H. 

Director


Research Subjects Protection


City of Hope/Beckman


Research Institute


Duarte, CA


Christine M. Parks, D.V.M., Ph.D. 

Director


Research Animal Resources Center


University of Wisconsin–Madison


Madison, WI


Ellen Paul 

Executive Director


The Ornithological Council


Washington, D.C.


Norman C. Peterson, D.V.M., Ph.D. 

Assistant Professor Comparative 

Medicine Johns Hopkins University 

Baltimore, MD 

Marky Pitts 

Director


Animal Subjects Program Director


Animal Research Information


University of California–San Diego


La Jolla, CA


Gregory R. Reinhard, D.V.M. 

Director, Comparative Medicine 

Schering-Plough Research Institute 

Kenilworth, NJ 

Harry Rozmiarek, D.V.M., Ph.D. 

Professor and Chief 

Laboratory Animal Medicine 

University Veterinarian 

University of Pennsylvania 

Philadelphia, PA 

William S. Stokes, D.V.M. 

Director


National Toxicology Program


Center for Alternative Methods


National Institute of Environ­


mental Health Sciences


Research Triangle Park, NC


Jim Swearengen, D.V.M. 

Chief


Veteri nary Medicine Division


USAMRIID, MCMR-UIR


Fort Detrick, MD


M. Michael Swindle, D.V.M. 

Professor & Chair 

Comparative Medicine 

Medical University of 

South Carolina 

Charleston, SC 

James F. Taylor, D.V.M., M.S. 

Director


Office of Animal Care and Use


National Institutes of Health


Bethesda, MD


Peter Theran, V.M.D. 

Vice President


Division of Health and Hospitals


Massachusetts Society for


the Prevention of Cruelty


to Animals, AHES


Boston, MA


John G. Vandenbergh, Ph.D. 

Department of Zoology


North Carolina State University


Raleigh, NC


Carol Wigglesworth 

Senior Policy Analyst


Office of Laboratory Animal Welfare


National Institutes of Health


Bethesda, MD

x 

Office of Laboratory Animal Welfare (OLAW) 

National Institutes of Health 

Office of the Director 

Nelson L. Garnett, D.V.M. 

Director 

Carol Wigglesworth 

Senior Policy Analyst 

Margaret Quinlan 

Animal Welfare Program Specialist 

Agnes Richardson 

Program Assistant 

Division of Compliance Oversight 

Stephen Potkay, V.M.D. 

Director 

Division of Assurances 

Denis Doyle 

Director 

Axel Wolff, M.S., D.V.M. 

Senior Assurance Officer 

Susann Machado 

Program Assistant 

Diana M. Lancaster 

Program Assistant 
xi 

Abbreviations and Acronyms 

Abbreviations 

Guide ILAR Guide for the Care and Use of Laboratory Animals 

PHS Policy PHS Policy on Humane Care and Use of Laboratory Animals 

Acronyms 

A 

AAALAC	 Association for Assessment and Accreditation of Laboratory 

Animal Care International 

AALAS American Association for Laboratory Animal Science 

AC Animal Care, APHIS, USDA 

ACLAM American College of Laboratory Animal Medicine 

AGRICOLA National Agricultural Library’s Agricultural OnLine Access (USDA) 

APHIS Animal and Plant Health Inspection Service (USDA) 

ARENA Applied Research Ethics National Association 

ASLAP American Society of Laboratory Animal Practitioners 

AV Attending Veterinarian 

AVMA American Veterinary Medical Association 

AWA Animal Welfare Act 

AWIC Animal Welfare Information Center 

AWRs Animal Welfare Regulations (USDA) 
xii Abbreviations and Acronyms 

C


CAAT Center for Alternatives to Animal Testing 

CCAC Canadian Council on Animal Care 

CDC Centers for Disease Control and Prevention 

CEO Chief Executive Officer 

CFA Complete Freund’s Adjuvant 

CFR Code of Federal Regulations 

CIRA Center for Information on Research with Animals 

CITES	 Convention on International Trade in Endangered 

Species of Wild Fauna and Flora 

D 

DHHS Department of Health and Human Services 

DOI Department of the Interior 

DVM/VMD Doctor of Veterinary Medicine or Veterinary Medical Doctor 

E 

EPA Environmental Protection Agency 

ESA Endangered Species Act 

F 

FASEB Federation of American Societies of Experimental Biology 

FBR Foundation for Biomedical Research 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 
Abbreviations and Acronyms xiii 

FOIA Freedom of Information Act 

FR Federal Register 

G 

GLP Good Laboratory Practices 

GPO Government Printing Office 

H 

HEPA High-Efficiency Particulate Air Filter 

HREA Health Research Extension Act, Public Law 99-158 

HVAC Heating, Ventilation and Air Conditioning 

I 

IACUC Institutional Animal Care and Use Committee 

IATA International Air Transport Association 

IBC Institutional Biosafety Committee 

ICLAS International Council for Laboratory Animal Science 

IFA Freund’s Incomplete Adjuvant 

iiFAR Incurably Ill for Animal Research 

ILAR Institute for Laboratory Animal Research 

IO Institutional Official 

IOM Institute of Medicine 

IRAC Interagency Research Animal Committee 
xiv Abbreviations and Acronyms 

L


LAMA Laboratory Animal Management Association


LAT Laboratory Animal Technician


LATg Laboratory Animal Technologist


LD Lethal Dose


LD50 Lethal Dose 50% 

M 

mAb Monoclonal Antibody 

MRI Magnetic Resonance Imaging 

N 

NABR National Association for Biomedical Research 

NAL National Agricultural Library 

NARRC National Advisory Research Resources Council 

NAS National Academy of Sciences 

NIH National Institutes of Health 

NIOSH National Institute of Occupational Safety and Health 

NRC National Research Council 

NSF National Science Foundation 

O 

OLAW Office of Laboratory Animal Welfare, NIH 

OHSP Occupational Health and Safety Program 
Abbreviations and Acronyms xv 

OMB Office of Management and Budget 

OSHA Occupational Safety and Health Administration 

OSTP Office of Science and Technology Policy 

P 

PHS Public Health Service 

PRIM&R Public Responsibility in Medicine and Research 

R 

RSC Radiation Safety Committee 

S 

SCAW Scientists Center for Animal Welfare 

U 

USDA U.S. Department of Agriculture 

USFWS U.S. Fish and Wildlife Service, Department of Interior 

V 

VA Department of Veterans Affairs 

W 

WHO World Health Organization 

WVA World Veterinary Association 
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A. The IACUC


1
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A.1. Timeline, Background and History 

Timeline 

1950 Formal establishment of Animal Care Panel. 

1963	 First edition of the Guide for the Care and Use of Laboratory Animals 

(Guide) developed by the Animal Care Panel. 

1965	 Incorporation of the American Association for the Accreditation of 

Laboratory Animal Care (AAALAC). 

1966	 Congress passed the Laboratory Animal Welfare Act (PL 89-544) 

and the USDA was named the responsible agency. 

1967	 Animal Care Panel changed its name to the American Association 

for Laboratory Animal Science (AALAS). 

1971	 NIH Policy on Humane Care and Use of Laboratory Animals for PHS 

Supported Institutions. 

1971	 USDA promulgated standards known as Subpart F, Stolen Animals 

(AWA). 

1973	 First Public Health Service (PHS) Policy on Humane Care and Use of 

Laboratory Animals. 

1974 Public Responsibility in Medicine and Research (PRIM&R) established. 

1979	 PHS Policy required each animal-using grantee institution to have a 

PHS Assurance and a committee to maintain oversight of its animal 

care program. 

1979	 USDA promulgated standards known as Subpart E, Identification of 

Animals (AWA). 

1982 First PRIM&R Animal Care and Use meeting. 

1985	 U.S. Government Principles for the Utilization and Care of Vertebrate 

Animals Used in Testing, Research and Training promulgated. 

1985 Health Research Extension Act (P.L.99-158) passed by Congress. 

3 
4 A. The IACUC 

1985 Animal Welfare Act Amendments passed by Congress. 

1986 Applied Research Ethics National Association (ARENA) established. 

1986 PHS Policy revised. 

1989	 USDA promulgated regulations (known as Parts 1 and 2) implement	

ing the 1985 AWA amendments. 

1990	 The structure of the Office for Protection from Research Risks (OPRR) 

was changed to establish a Division of Animal Welfare. 

1990	 USDA promulgated standards known as Subpart B, Registration and 

Subpart C, Research Facilities (AWA). 

1991	 USDA promulgated standards known as Part 3. In addition, amend	

ments were made to Part 2: Regulations in Subpart A, Licensing and 

Subpart D, Attending Veterinarian and Adequate Veterinary Care. (AWA). 

1992	 First Institutional Animal Care and Use Committee Guidebook was 

developed by a committee under the auspices of the Applied Research 

Ethics National Association (ARENA) and OPRR. 

1996	 7th Edition of the Guide for the Care and Use of Laboratory Animals 

revised by an ILAR committee and published by the NRC. 

1996	 AAALAC became the Association for the Assessment and Accredita	

tion of Laboratory Animal Care International. 

2000	 OPRR Division of Animal Welfare was separated from OPRR and 

became the Office of Laboratory Animal Welfare (OLAW), NIH. 

2002	 ARENA/OLAW Institutional Animal Care and Use Committee Guidebook. Second edition. 
A.1. Timeline, Background and History 5 

Background and History 

Prior to the middle of the 20th century the responsibility for animals used 

in research in the United States was placed directly in the hands of the 

researchers and the quality of animal care and animal welfare varied 

tremendously among research institutions. Even within the same school 

or institution, research laboratories had inconsistent animal care policies 

and standards of care. 

In 1961, a group of veterinarians working for research institutions in the 

Chicago area formed the Animal Care Panel (ACP). The ACP appointed a 

committee charged with establishing animal care and use guidelines for 

research facilities. Their product was the publication of the first edition 

(1963) of the Guide for the Care and Use of Laboratory Animals (referred to 

in this document as the Guide). Subsequent editions of this publication 

were supported by the NIH and developed under the auspices of the 

Institute of Laboratory Animal Resources (ILAR), which was subsequently 

renamed the Institute for Laboratory Animal Research. The National Acad	

emy Press, under the auspices of the National Research Council, published 

the most recent (seventh) edition in 1996. This single document serves as 

the primary source of laboratory animal care and use standards and 

guidelines in the United States. The 1996 edition has been translated 

and published in six languages, and over 400,000 copies have been 

distributed throughout the world. 

In 1963, the ACP saw a need to evaluate the standards of animal care and 

use practiced in research institutions based on the Guide, and appointed 

an Animal Accreditation Committee. This Committee soon determined 

that it should function independently of the ACP, and in 1965 incorporated 

in the state of Illinois as the American Association for the Accreditation 

of Laboratory Animal Care. This independent accrediting agency changed 

its name in 1996 to the Association for the Assessment and Accreditation 

of Laboratory Animal Care International (AAALAC). 

Prior to 1966, no U.S. federal law addressed laboratory animal welfare. 

Local humane societies actively promoted responsible treatment of pets 

and farm animals. Concurrently, the scientific community was improving 

the quality of animal care and well-being in the research laboratory. During 

this time the increasing need for dogs and cats in research was partially 

fulfilled by animal dealers who obtained these animals in various ways 

and sold them to research laboratories. A series of articles and news 
6 A. The IACUC 

reports on animal neglect, abuse and pet theft by animal dealers culmi	

nated in a 1966 major article and photographs in Life magazine. The article 

suggested a need for regulation and a system of enforcement, especially 

for dogs and cats used in research. Catalyzed in part by this article, the 

Laboratory Animal Welfare Act, the first version of what is now known as 

the Animal Welfare Act (AWA), was passed by Congress in 1966 (Public 

Law 89-544) establishing legal standards for laboratory animal care and 

use for the first time in this country. The United States Department of 

Agriculture (USDA) was named the responsible agency for implementing 

and enforcing this new law and it promptly began promulgating regula	

tions. Research laboratories and dealers were required to register or license 

their facilities and undergo inspection by USDA personnel who were 

authorized to issue citations for non-compliance. These early inspections 

did not extend into the research laboratory where animal care and use 

remained under the direction of the research investigator. A number of 

amendments to the AWA have led to regulations that now include animal 

transportation, marine mammals, and animals in the research laboratory. 

However, the USDA regulations currently exclude common laboratory rats 

(Rattus norvegicus) and mice (Mus musculus), birds, and farm animals used 

in production agriculture research. 

All Public Health Service (PHS) policies on this subject evolved from the 

1971 National Institutes of Health (NIH) Policy, “Care and Treatment of 

Laboratory Animals.” That policy referenced several NIH and PHS state	

ments on appropriate care and humane treatment of laboratory animals, 

among them the Guide. It introduced the animal care committee as a 

means of local assurance of good animal care and use. 

The 1971 NIH policy required institutions or organizations using warmblooded animals in research or teaching supported by NIH grants, awards 

or contracts to “assure the NIH that they will evaluate their animal facilities 

in regard to the maintenance of acceptable standards for the care, use 

and treatment of such animals.” The institution could show that it was 

either accredited by a recognized professional laboratory animal accredit	

ing body (AAALAC) or had established an animal care committee to carry 

out that assurance function. The minimum number of committee members 

was not stated, but at least one member had to be a Doctor of Veterinary 

Medicine. Guidelines for the committee included the Guide, all applicable 

portions of the AWA, and an appended set of Guidelines known as the 

“Principles for the Use of Laboratory Animals.” The committee was required 
A.1. Timeline, Background and History 7 

to inspect the institution’s animal facilities at least once a year and report 

its findings and recommendations to responsible institutional officials. 

Records of activities and recommendations were required to be available 

for inspection by NIH representatives. 

The first PHS policy regarding animal care and use replaced the NIH 

policy on July 1, 1973 and continued to accept AAALAC accreditation in 

lieu of an institutional committee. The January 1, 1979 revision of the PHS 

policy required each animal-using grantee institution to have “a committee 

to maintain oversight of its animal care program” and expanded the defini	

tion of animal to include all vertebrates. The revised policy also required 

an institution to submit an Assurance statement to the Office for Protection 

from Research Risks (OPRR), now the Office of Laboratory Animal Welfare 

(OLAW), that it is committed to follow the Guide, the Principles and the 

PHS policy requirements, before receiving PHS support for studies in which 

animals or animal facilities were used. 

Institutions were required to include in their Assurance a list of committee 

members with their position titles and credentials. Committees were 

composed of at least five members including at least one veterinarian. The 

members had to be knowledgeable regarding the care and use of animals 

used in research. 

The 1979 PHS policy continued to accept AAALAC accreditation as a 

means of demonstrating conformance with the Guide, but an alternative 

was annual review of the animal facilities and procedures by the institution’s 

IACUC. Institutions were required to report to NIH (OPRR) any noncon	

formance with the Guide or problems encountered in implementing the 

PHS policy, and submit annual reports indicating progress toward full 

conformance. Review of individual proposals or projects by the IACUC 

was encouraged but not required. 

The most recent revision, officially the PHS Policy on Humane Care and 

Use of Laboratory Animals (referred to in this document as the PHS Policy), 

was promulgated in 1986 and reprinted in 1996 and 2000. It further defined 

and outlined requirements of an animal care and use program. This revised 

PHS Policy includes provisions of the Health Research Extension Act of 

1985, enacted on November 20, 1985 as Public Law 99-158. The 1986 

PHS Policy applies to both extramural and intramural PHS research and 

requires the Institutional Animal Care and Use Committee (IACUC) mem	

bers to be appointed by the Chief Executive Officer of the institution. The 
8 A. The IACUC 

IACUC must evaluate and prepare reports on all of the institution’s programs and facilities (including satellite facilities) for activities involving 

animals at least twice each year, and is required to review the care and use 

of animals in PHS-supported activities. The IACUC, through the Institutional 

Official (IO), is responsible for compliance with reporting requirements. 

Minority views filed by members of the IACUC must be included in 

reports filed under this PHS Policy. The PHS Policy also requires training or 

instruction for scientists, animal technicians and other personnel involved 

in animal care, treatment or use. This training or instruction must include 

information on the humane practice of animal care and use as well as train	

ing or instruction in research or testing methods that minimize the number 

of animals required to obtain valid results and minimize animal distress. 

The Interagency Research Animal Committee, made up of representatives 

of federal agencies that use or require the use of experimental animals, 

promulgated the “U.S. Government Principles for the Utilization and Care 

of Vertebrate Animals Used in Testing, Research and Training” in 1985 

(see Appendix F). These Principles were subsequently incorporated into 

the 1986 PHS Policy, and remain in effect today as a model for federal 

agencies that develop specific agency policies for the use of animals. 

With the promulgation of the 1986 version of the PHS Policy, OPRR (now 

OLAW) embarked upon an extensive national education program. The 

program began with the co-sponsorship of one- to two-day workshops in 

conjunction with Assured institutions at different geographical locations. 

Many of the early workshops focused on basic provisions set forth in the 

1986 PHS Policy, such as protocol review and semiannual program evalu	

ations. That cosponsorship of approximately four to five workshops a 

year continues today, although the topics are now generally more special	

ized, covering areas such as performance standards, field studies, and 

laboratory animal management and technology. Since 1995 OLAW has 

expanded its educational role to include development of a Web-based 

tutorial, an extensive Web site with sample documents to assist institu	

tions in their implementation of the PHS Policy, co-sponsorship of ARENA’s 

IACUC 101 program, and this revised ARENA/OLAW Guidebook. 

Special interest groups concerned about the acquisition and welfare of 

animals used in research continue to influence research animal care and 

use. These groups include local and national humane societies concerned 

about animal welfare and well-being, and antivivisectionist groups that 

are opposed to the use of animals in research. The activity of some animal 
A.1. Timeline, Background and History 9 

rights groups escalated and became more vocal in the early 1980s. This 

activity peaked in a series of illegal break-ins and vandalism and was brought 

to the forefront of public opinion soon after two incidents involving alleged 

“animal cruelty” and “insensitivity” in two well-known research institutions. 

This climate raised public concern and visibility of animals in research and 

served as a catalyst for amendments and clarifications of guidelines and 

regulations providing for animal welfare. 

New USDA regulations based on the 1985 amendment to the AWA 

became effective between October 1989 and August 1991. These regula	

tions require each registered research institution to appoint an IACUC of 

not less than three members, including a veterinarian, which “serves as 

the agent of the research facility that assures that the facility is in full com	

pliance with the Act.” The regulations also require a member not affiliated 

with the institution representing community interests in the proper care 

and treatment of animals. These USDA Animal Welfare Regulations (AWRs) 

and the PHS Policy contain many common requirements. 

The Scientists Center for Animal Welfare (SCAW) was instrumental in pro	

viding early guidance to institutions on IACUC functions and organization 

through regional conferences and workshops, culminating in a special 

1987 American Association for Laboratory Animal Science (AALAS) publi	

cation entitled, “Effective Animal Care and Use Committees.” Since 1983, 

training and guidance of this type has also been provided through annual 

animal care and use conferences sponsored by Public Responsibility in 

Medicine and Research (PRIM&R) and the Applied Research Ethics 

National Association (ARENA), regional workshops supported by OLAW, 

and numerous similar activities. The first Institutional Animal Care and Use 

Committee Guidebook was written by a committee of experts under the 

auspices of ARENA and published by NIH in 1992. The present edition, 

published in 2002, is the first revision. 

During the 1990s there was an evolution in the ways that IACUCs fulfilled 

their mandate. This was in part due to increased experience implement	

ing the PHS Policy and AWRs, but may also be attributed to new reports, 

such as the 1996 Guide which emphasizes performance goals as opposed 

to engineering standards, and the 1997 ILAR report, Occupational Health 

and Safety in the Care and Use of Research Animals, that shifted the focus 

of occupational health programs to risk based systems. Other factors 

contributing to this evolution came from the research community, such 

as the development of transgenic animals and in vitro alternatives to the 
10 A. The IACUC 

production of monoclonal antibodies. The IACUC community has also 

gained a greater understanding of and appreciation for the role of nonaffili	

ated and nonscientific IACUC members. Humane endpoints in research 

and innovative ways to address environmental enrichment of primates 

are other areas that grew in sophistication during the 1990s. Training of 

IACUC members and animal users has received greater attention and the 

number of training programs and modules has increased significantly. 

Finally, OLAW, USDA and AAALAC International have all placed an increased focus on IACUC functions. 

While originally borrowed from the human Institutional Review Board 

structure, the concept of IACUCs to review and ensure animal welfare is 

now common practice in the animal research community. The goal of each 

IACUC is to ensure the humane care and use of animals used in research, 

and compliance with guidelines and regulations, while maintaining flexi	

bility to best meet the unique needs of the institution. Active participation 

by research scientists allows for the scientific needs of research investi	

gators to be considered; participation by nonaffiliated members incorpo	

rates a public conscience; and the involvement of veterinarians ensures 

appropriate medical care and animal well-being. A program of continuing 

education is essential to ensure that animal care and use standards and 

ethical principles continue to be applied at the highest possible level. 

References


Wayman, Stan. February 4, 1966. Concentration Camps for Dogs. LIFE 60:5:22-29.­

Care and Treatment of Laboratory Animals. June 14, 1971. (NIH 4206). NIH Guide 

for Grants and Contracts, No. 7. 

National Institutes of Health Policy on Humane Care and Use of Animals. Effective 

January 1, 1979. (NIH 4206). 

U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used 

in Testing, Research and Training. May 20, 1985. 50 FR 20864. 

Institutional Animal Care and Use Committee Guidebook. 1992. NIH Pub. No. 92-

3415. U.S. Department of Health and Human Services. Washington, DC. 

Fraser, Caroline. April 19, 1993. The Raid at Silver Spring. The New Yorker 66-84. 

McCabe, Katie. August 1986. Who Will Live, Who Will Die. The Washingtonian 21:11. 

Orlans, F., R. Simmonds and W. Dodds. 1987. Effective Animal Care Committees. 

Scientists Center for Animal Welfare. Laboratory Animal Science. 
A.2. Authority, Composition and Functions 

Each institution that receives PHS support for activities involving vertebrate 

animals or is subject to the authority of the Animal Welfare Act (AWA) must 

operate an animal care and use program with clear lines of authority and 

responsibility. The program must include: 

•
 a properly constituted and functioning Institutional Animal Care and 

Use Committee (IACUC); 

• procedures for self monitoring; 

• an adequate veterinary care program; 

• an occupational health and safety program (not required under the AWA); 

• a personnel training program; 

• an environment, housing and management program for animals; and 

• appropriately maintained facilities for housing and support. 

PHS requires an institutional Animal Welfare Assurance that provides 

details on the institutional program in order to award funds; USDA requires 

registration of facilities. Section E.1. and E.1. Table B include additional 

detail concerning PHS assurances and USDA registration. 

Authority 

IACUCs derive their authority from the law. They are mandated by the Health 

Research Extension Act (HREA) of 1985 and the AWA. The laws require 

the Chief Executive Officer (CEO) of an organization to appoint the IACUC, 

whose responsibilities are delineated in the law and federal policy and 

regulations. Office of Laboratory Animal Welfare (OLAW) considers the 

CEO to be the highest operating official of the organization. The CEO may 

delegate authority to appoint the IACUC if the delegation is specific and 

in writing. 

Once appointed, IACUCs report to a senior administrator known as the 

Institutional Official (IO). The IO must have administrative and operational 

authority to commit institutional resources to ensure compliance with the 

PHS Policy and other requirements. The CEO and IO may be the same 

11 
12 A. The IACUC 

individual, although at large institutions the CEO is typically somewhat 

removed from operational program involvement. Occasionally IOs are 

also appointed to serve on IACUCs but this is not advisable because the 

IACUC reports to the IO, creating potential conflict of interest. 

The IACUC’s mandate to perform semiannual program evaluations as a 

means of overseeing the animal care and use program puts the IACUC in 

an advisory role to the IO. In its semiannual reports the IACUC advises 

the IO of the status of the institution’s compliance, establishes plans 

and schedules for correcting deficiencies necessary to either maintain or 

achieve compliance, and makes recommendation to the IO regarding any 

aspect of the institution’s animal program, facilities, or personnel training. 

This approach of “enforced self-regulation” requires that the IACUC have 

the full support of the IO responsible for the program. 

The IACUC’s authority to review and approve protocols is independent 

of the IO who may not overrule an IACUC decision to withhold approval of 

a protocol. (The converse is not true, i.e., if an IACUC approves a pro	

tocol the institution is not required or obligated to conduct the research 

activity.) An institution may subject protocols to additional institutional 

review (e.g., department head, biosafety committee, etc.) 

Committee Composition 

Some IACUC members fulfill specific regulatory requirements (e.g., 

veterinarian with program responsibility, an individual nonaffiliated with 

the institution); others have unique roles by virtue of their position (e.g., 

chairperson). 

There are no specific prohibitions regarding individuals filling more than 

one role on the IACUC, but OLAW strongly recommends against the same 

person serving multiple roles because the responsibilities and authorities 

vested in each of the positions are distinct and often require different 

skills. Appointing one individual to more than one of these roles may 

circumvent intended checks and balances. Also of importance is the 

perception of conflict of interest, which can lead to allegations of impropri	

eties from various sources. 

Veterinarian: The PHS Policy and AWRs mandate the appointment of a 

veterinarian with direct or delegated program responsibility to the IACUC. 

CEOs may appoint more than one veterinarian to the IACUC but the veteri	

narian with direct or delegated program responsibility must be designated 
A.2. Authority, Composition and Functions 13 

as such. The veterinarian with program responsibility must have training or 

experience in laboratory animal science and medicine or in the care of the 

species being used. 

Chair: A knowledgeable and effective leader is crucial to an effective 

IACUC. This individual needs the full support of the IO. A chair with suffi	

cient stature (e.g., seniority or tenure) can perform the functions of this 

position without jeopardy to his/her career. In the case of a large program 

of animal care and use a co-chair may be desirable. 

Nonaffiliated member: The nonaffiliated member is intended to repre	

sent general community interests. An informed nonaffiliated member can 

bring significant value to the committee by bringing a non-institutional 

perspective to the research endeavor. This member has equal status to 

every other committee member and should be provided the opportunity 

to participate in all aspects of IACUC functions. 

While in the majority of instances effective nonaffiliated members may 

be willing to serve without reimbursement, in other instances remunera	

tion for expenses or compensation for time may allow for participation 

by effective individuals that would not otherwise be possible. OLAW and 

USDA maintain that nominal compensation is permissible without jeopar

dizing a member’s non-affiliated status, if it is only in conjunction with 

service on the IACUC and if the amount of compensation is not so sub	

stantial that it could be considered to influence voting on the IACUC. 

Scientist and nonscientist: PHS Policy requires that the IACUC include a 

practicing scientist experienced in research involving animals, and a 

member whose primary concerns are in a nonscientific area. Examples of 

the latter include, but are not limited to, ethicist, lawyer, member of the 

clergy, and librarian. 

Institutions should consider persons with expertise in the disciplines 

involved in institutional research and teaching programs for service on 

their IACUCs. In addition to the required categories of membership, it is 

suggested that individuals with expertise in specific areas pertinent to 

protocol review and program oversight be considered (e.g., statisticians, 

occupational health experts, information resource specialists, animal health 

technicians, and scientific research staff). 

There is no requirement that any particular member or category of 

members be present at all IACUC meetings. However, an institution must 

have a properly constituted IACUC in order for the IACUC to conduct valid 
14 A. The IACUC 

official business. Many institutions have found that appointing more than 

the minimum number of members who meet the respective criteria obvi	

ates problems when an unexpected vacancy occurs, and can help the 

committee meet the quorum requirements necessary for certain official 

committee actions. 

A.2. Table A. Comparison of IACUC Membership Requirements 

PHS Policy USDA Regulations 

PHS Policy IV.A. 3. a., b. 9 CFR, 2.31 (a) (b) 

Appointed by the CEO Appointed by the CEO 

Minimum of five members: Minimum of three members: 

One Doctor of Veterinary Medicine with 

training or experience in laboratory animal 

science and medicine who has direct or 

delegated program authority and respon	

sibility for activities involving animals at 

the institution. 

One practicing scientist experienced 

in research involving animals. 

One member whose primary concerns 

are in a nonscientific area (for example, 

ethicist, lawyer, clergy). 

One member not affiliated in any way with 

the institution and not a member of the 

immediate family of a person who is 

affiliated with the institution. 

The PHS Policy requires institutions 

to follow the Guide, which states that 

committee membership should include 

at least one public member to represent 

general community interests in proper 

care and use of animals, and that public 

members should not be laboratory 

animal users. 

At least one Doctor of Veterinary Medicine 

with training or experience in laboratory 

animal science and medicine, and who 

has direct or delegated program respon	

sibility for activities involving animals at 

the institution. 

One member not affiliated in any way 

with the institution and not a member 

of the immediate family of a person who 

is affiliated with the institution; person 

who represents the general community 

interests in the proper care and treatment 

of animals; and is not a laboratory animal 

user (USDA Policy # 15) 

Not more than three members from the 

same administrative unit of the institution. 
A.2. Authority, Composition and Functions 15 

Alternate members may be appointed to the IACUC as long as they are 

appointed by the CEO or other official with authority to appoint members, 

and there is a specific one-to-one designation of IACUC members and 

alternates. An IACUC member and his/her alternate may not count toward 

a quorum at the same time or act in an official member capacity at the 

same time. Alternates should receive training similar or identical to the 

training provided to regular IACUC members. 

Conflict of Interest 

Both the AWRs and PHS Policy state that no IACUC member “may par

ticipate in the IACUC review or approval of an activity in which that 

member has a conflicting interest, (e.g., is personally involved in the 

activity) except to provide information requested by the IACUC.” 

If the investigator submitting a protocol believes that an IACUC member 

has a potential conflict, the investigator may request that the member be 

excluded. When a member has a conflict of interest, the member should 

notify the IACUC Chair and may not participate in the IACUC review or 

approval except to provide information. Members who have a conflict of 

interest may not be counted toward a quorum and may not vote. 

Other possible examples of conflict of interest include cases where: 

• a member is involved in a potentially competing research program, 

•
 access to funding or intellectual information may provide an unfair 

competitive advantage, or 

•
 a member’s personal biases may interfere with his or her impartial 

judgment. 

Quorum Requirements 

Certain official IACUC actions require a quorum: full committee review of 

a research project (Policy IV.C.2. and AWR §2.31(d)(2)) and suspension of 

an activity (Policy IV.C.6. and AWR §2.31(d)(6)). “Quorum” is defined as 

a majority (>50%) of the voting members of the IACUC. Therefore, a 

protocol is approved only if a quorum is present, and if more than 50% 

of the quorum votes in favor. PHS Policy and AWRs require that in order 
16 A. The IACUC 

to suspend an activity, the IACUC must review the matter at a convened 

meeting of a quorum of the IACUC and the suspension must be approved 

by a majority vote of the quorum present. 

For reasons other than conflict of interest, abstentions from voting do 

not alter the quorum or change the number of votes required. For example: 

If an IACUC has 20 voting members, at least 11 members must be 

present at a convened meeting to constitute a quorum and approval of 

a protocol would require a minimum of six votes whether or not there 

were abstentions. 

The requirements of the PHS Policy and AWRs take precedence even 

though they may differ from some commonly used parliamentary proce	

dures. Institutions may develop their own meeting procedures as long as 

the procedures do not contradict or are not inconsistent with the require	

ments of the PHS Policy or the AWRs. 
A.2. Authority, Composition and Functions 17 

A.2. Table B. Federally Mandated Functions of the IACUC 

PHS USDA 

PHS Policy. IV.B.1-8 9 CFR. 2.31 (c) (1) – (8) and 2.31(d) (5) (6) & (7) 

1. Review, at least once every six months, 

the research facility’s program for the 

humane care and use of animals, using 

the Guide as a basis for evaluation. 

2. Inspect, at least once every six months, 

all of the institution’s animal facilities 

(including satellite facilities) using the Guide 

as a basis for evaluation. Satellite holding 

facilities (a facility outside of a core facility 

or centrally designated area in which 

animals are housed for more than 24 hours) 

and areas in which surgical manipulations 

are performed must always be included. 

3. Prepare reports of the IACUC evalua	

tions and submit the reports to the IO. 

The reports must contain a description 

of the nature and extent of adherence to 

the Guide and PHS Policy and identify 

specifically any departures from the provisions of the Guide and PHS Policy and 

state reasons for each departure. The 

IACUC may determine the best means 

of conducting an evaluation of its program 

and facilities. The IACUC may invite ad hoc 

consultants to assist in conducting the 

evaluation. However, the IACUC remains 

responsible for the evaluation and report. 

Reports must distinguish significant 

deficiencies from minor deficiencies and 

must contain a reasonable and specific 

plan and schedule for correcting each 

deficiency. A significant deficiency is one 

that is or may be a threat to the health 

and safety of the animals. Reports must 

be made available to OLAW upon request. 

4. Review concerns involving the care 

and use of animals at the institution. 

1. Review, at least once every six months, 

the research facility’s program for humane 

care and use of animals, using title 9, 

chapter 1, subchapter A—Animal Welfare, 

as a basis for evaluation. 

2. Inspect, at least once every six months, 

all of the research facility’s animal facilities, 

including animal study areas, using title 9, 

chapter 1, subchapter A—Animal Welfare 

as a basis for evaluation. Areas where 

animals are housed for more than 12 hours 

are defined as “study areas.” 

3. Prepare reports of its evaluations (using 

the title 9, chapter 1, A – AWR) and submit 

to the IO. The IACUC may determine the 

best means of conducting evaluations of 

the research facility’s programs and 

facilities, provided that no member wishing 

to participate in any evaluation is excluded. 

Reports must distinguish significant 

deficiencies from minor deficiencies and 

must contain a reasonable and specific plan 

and schedule with dates for correcting each 

deficiency. A significant deficiency is one 

that is or may be a threat to the health and 

safety of the animals. A significant defi	

ciency remaining uncorrected beyond the 

scheduled correction date shall be reported 

in writing within 15 business days by the 

IACUC, through the IO, to APHIS and any 

federal agency funding that activity. Reports 

must be made available to APHIS and to 

officials of federal funding agencies for 

inspection and copying upon request. 

4. Review, and if warranted, investigate 

concerns involving the care and use of 

animals resulting from public complaints 

and from reports of noncompliance 

received from laboratory or research 

facility personnel or employees. 

continued on page 18 
18 A. The IACUC 

A.2. Table B. Federally Mandated Functions of the IACUC (continued) 

PHS USDA 

PHS Policy. IV.B.1-8 9 CFR. 2.31 (c) (1) – (8) and 2.31(d) (5) (6) & (7) 

5. Make recommendations to the IO 

regarding any aspect of the animal 

program, facilities or personnel training. 

6. Review and approve, require modifi	

cations in, or withhold approval of those 

components of PHS-conducted or supported animal care and use activities. 

A complete review is required at least 

once every three years. 

7. Review and approve, require modifica	

tions in, or withhold approval of proposed 

significant changes regarding the use of 

animals in ongoing activities. 

8. Be authorized to suspend an activity 

involving animals in accordance with 

specifications in IV.C.6 of PHS Policy (i.e., 

an activity that is not being conducted in 

accordance with applicable provision of 

the AWA, the Guide, the institution’s 

Assurance, or PHS Policy.) This action 

may be taken only after review of the matter 

at a convened meeting of a quorum of the 

IACUC and a vote for suspension by the 

majority of the quorum present. The IO in 

consultation with the IACUC shall review 

the reasons for suspension, take appro	

priate corrective action, and report that 

action with a full explanation to OLAW. 

5. Make recommendations to the IO 

regarding any aspects of the animal 

program, facilities or personnel training. 

6. Review and approve, require modifi	

cations in, or withhold approval of those 

components of proposed activities related 

to the care and use of animals. Continu	

ing review of activities required not less 

than annually. 

7. Review and approve, require modifica	

tions in, or withhold approval of proposed 

significant changes regarding the care 

and use of animals in ongoing activities. 

8. Be authorized to suspend an activity 

involving animals if it determines that the 

activity is not being conducted in accor

dance with the description provided by 

the investigator and approved by the 

IACUC. This may be done only after 

review at a convened meeting of a 

quorum of the IACUC with the suspen	

sion vote of a majority of the quorum 

present. The IO, in consultation with the 

IACUC, shall review the reasons for the 

suspension, take appropriate corrective 

action, and report that action with a full 

explanation to APHIS and any federal 

agency funding that activity. 

References 

The Public Health Service Responds to Commonly Asked Questions. Fall 1991. 

ILAR News Volume 33(4):68-70. 

Robb, J. Wesley. 1993. Personal Reflections: The Role and Value of the Unaffiliated 

Member and the Non Scientist Members of the IACUC. ILAR News Volume 35:3-4. 

OPRR Reports. 1997. 97-03, June 2, 1997. 

NIH Guide for Grants and Contracts, Notice OD-01-017. February 12, 2001. 

Frequently Asked Questions about The PHS Policy on Humane Care and Use 

of Laboratory Animals. Summer/Fall, 1993. ILAR News Volume 35(3-4):47-49. 

Protocol Review. A Note from the NIH and USDA. 1996. Lab Anim 25(5)22. 
A.3. Operation and Administration 

Institutional Responsibility for Animal Welfare 

Assuring laboratory animal welfare necessitates a partnership among 

the Institutional Official (IO), the IACUC, the veterinarian and the investiga	

tors. Ultimately, accountability for assuring humane care and use of 

animals resides with the institution, but this may only be achieved when all 

of the players, i.e., the investigators and their research staff, the veterinary 

staff, animal caretakers and technicians, and the IACUC, contribute to a 

shared goal. 

Each institution should provide a framework with appropriate resources for 

an animal care and use program that is managed in accordance with the 

PHS Policy, the Guide, and the Animal Welfare Regulations (AWRs). Organi	

zations that function effectively have simple, clear and direct lines of 

responsibility and corresponding authority. 

AWA–HREA 

AWRs–PHS Policy 

Institutional Official 

Veterinarian 

Animal Care 

Program 

Chair 

IACUC IACUC 

Office 

Investigator 

Research Staff 

Components of an animal care and use program. Heavy lines represent the mandate from 

the Animal Welfare Act and Health Research Extension Act that the Secretaries of Agricul	

ture and Health and Human Services develop guidelines for the use of animals in research 

and for IACUCs, and require established lines of authority from the IO to the IACUC, IACUC 

staff, and veterinarian. Dotted lines represent the need for cooperation and communication 

among components. 

19 
20 A. The IACUC 

The PHS Policy and AWRs place a strong emphasis on senior management 

level responsibility and on use of the IACUC as an oversight committee to 

evaluate the program. The committee needs to work closely with the animal 

users, the animal care staff, and the responsible veterinarians to ensure a 

high quality animal care and use program. The IO must support the IACUC 

by providing appropriate resources. 

Responsibilities of the Institutional Official 

The IO must have the authority to allocate organizational resources needed 

to maintain a smoothly functioning animal care and use program based on 

the recommendations and advice received from: 

• the IACUC, 

• the veterinarian, and 

• the IACUC professional and administrative staff. 

The IO should also clearly define and assign responsibilities and reporting 

channels for other essential program elements such as: 

• personnel training,­

• occupational health and safety, and­

• maintenance of facilities. 

The IACUC, appointed by the organization’s Chief Executive Officer (CEO), 

must report directly to the IO and be empowered to perform its duties 

without undue interference. OLAW’s experience is that it is usually best for 

the veterinarian also to report directly to the IO in connection with his or 

her responsibility for implementing the animal care and use program. In 

order to provide the intended checks and balances in the system of selfregulation, it is advisable that the veterinarian not serve as Chair of the 

IACUC or as IO. While it is important that there be a collegial and effective 

working relationship between the IACUC and the veterinarian, it is impor

tant to avoid the potential for real or perceived conflicts of interest. 
A.3. Operation and Administration 21 

Role and Responsibilities of the IACUC Staff 

The nature of the institution and the volume of animal-based research 

determine the staffing requirements of an IACUC and the animal care 

program. Institutions with a high volume of proposals involving animals may 

require full time IACUC staff. A professional staff with expertise in animal 

welfare laws, regulations and policies is especially important to provide 

stability and continuity to animal care and use programs where IACUC chairs 

and members serve on a rotating basis. 

The role of the IACUC staff is to provide administrative support to the IACUC 

and the IO. It is important however, that neither the IO nor the IACUC Chair 

over-invest authority or responsibility in the IACUC staff. 

The IACUC staff often serve as the gatekeepers of information and com	

munications for the IO, the IACUC Chair and members, the veterinarian, the 

animal resource program, the investigators, and other offices within the 

institution such as public relations and sponsored research. It is important 

that training and continuing education be provided to program staff so they 

are knowledgeable of current animal care and use policies and regulations 

and aware of proposed changes. OLAW workshops, ARENA and PRIM&R 

annual meetings, ARENA IACUC 101 Training, and SCAW meetings, are 

examples of useful training and educational opportunities. 

IACUC staff responsibilities range from clerical and administrative to pro	

fessional, depending on the size and complexity of the program. 

Some examples of clerical tasks are: 

• data entry; 

• screening protocols for completeness; 

•
 preparing agendas and distributing protocols and other materials 

to IACUC members; 

• sending out reminders of protocol expirations and approval letters; 

•
 maintaining records of protocols and minutes of the meetings, 

policies and procedures, program reviews and facility inspection 

reports; and 

•
 coordinating and scheduling the IACUC’s meetings, facilities inspec	

tions and laboratory site visits. 
22 A. The IACUC 

Administrative duties include: 

•
 preparation of minutes and other correspondence and reports, 

such as the PHS Assurance document, and annual PHS, USDA and 

AAALAC reports; and 

•
 serving as an information resource for investigators and IACUC 

members regarding regulatory issues and the status of protocols. 

Professional staff duties include: 

• providing orientation and training of new IACUC members; 

•
 grant proposal review to ensure consistency in the animal care and 

use components of the proposal and the protocol submitted to 

the IACUC; 

•
 pre-review of protocols for federal assurances, scientific and statis	

tical validity; 

• review of literature searches; and 

• drafting of institutional policies. 

The IACUC staff also maintains federal documents such as the institution’s 

PHS Assurance, USDA registration and reports, and AAALAC accredita	

tion materials. 

Review of Grants and Contracts Submitted to PHS 

In order to approve a protocol that involves the use of animals, the IACUC 

must review the proposed care and use of animals and determine that 

federal criteria have been met. PHS requires that the project be conducted 

in accordance with the PHS Policy, the AWA, the Guide, the institution’s 

Assurance, and all other applicable federal statutes and regulations related 

to animals. The project should also comply with all institutional policies. 

Most IACUCs require use of a standardized protocol application form to 

assist the investigator in providing the information necessary to ensure 

compliance. While there is no explicit requirement for the IACUC to do a 

side-by-side comparison of the information contained in the IACUC proto	

col review form and the information submitted to PHS, it is imperative that 

the protocol that the IACUC approves is consistent with the information 

submitted to PHS. Institutions should devise a mechanism to verify that 

consistency. If the IACUC requires changes to the protocol that are not 
A.3. Operation and Administration 23 

reflected in the grant application, then the PHS funding component must 

be notified in the follow-up certification of IACUC approval. 

Institutions are required to provide PHS with the date of IACUC approval. 

There is no provision for providing a contingent approval date; the date 

provided must signify full approval by the IACUC. If an institution has a PHS 

Assurance, then in most cases the PHS allows a 60-day grace period 

following the receipt deadline date during which the investigator may 

secure IACUC approval; otherwise, the application cannot be peer reviewed. 

If the IACUC review occurs subsequent to the grant submission, then 

a letter verifying IACUC approval, and stating any modifications required by 

the IACUC, must be submitted to the funding agency. This grace period 

is non-existent for some non-federally funded projects and investigators 

are required to submit evidence of IACUC approval coincident with the grant 

or contract submission. 

If an institution does not have a PHS Assurance, the signature of the official 

signing the grant application for the organization constitutes a declaration 

that the institution will submit an Assurance and verification of IACUC 

approval upon request by OLAW. 

Responsibility for Collaborations and Subcontracted Research 

Collaborations between institutions can sometimes create ambiguity regard	

ing responsibility for animal welfare. In cases where an individual investiga	

tor has appointments at several institutions, or where collaborations occur 

between institutions, it is advisable to have a formal written agreement, 

contract or memorandum of understanding between the institutions. This 

document should originate from the primary collaborative institution (i.e., 

the institution primarily responsible for directing and/or funding the research) 

and be signed by the secondary institution. 

When an institution receiving PHS funds contracts with a commercial 

vendor using animals to produce a product, there may need to be IACUC 

involvement. If a company produces standard antibodies for general sale, 

that company is not required to file an Assurance with OLAW. However, if 

a supplier or contractor produces antibodies in animals using an anti	

gen provided by or at the request of an investigator, the antibodies are 

considered “custom” and the vendor must have an Assurance on file. The 

vendor Assurance must be identified on the PHS grant application, and 

the awardee institution is responsible for verifying that the work is done at 

an Assured institution. 
24 A. The IACUC 

In addition, while the approaches of funding and regulatory agencies are 

complementary, they also differ. The PHS Policy invests responsibility for 

animals in the entity that receives PHS funding, known in grant parlance as 

the “awardee” or “grantee” institution. Accordingly, if there is a concern 

about a PHS-funded animal activity PHS will likely “follow the money” to 

determine institutional accountability. Under the AWRs, responsibility 

generally resides with the institution that houses the animals and with the 

institution that owns the animals, which may not be the same institution. 

PHS may award funds for an activity involving animals only to an entity that 

has an approved PHS Assurance. When more than one institution is in	

volved, one of the following four scenarios generally apply: 

•
 An awardee institution and/or a subcontractor or collaborating insti	

tution can both have PHS Assurances. In this situation, two assured 

entities are responsible for determining which IACUC will review the 

research and under which institutional program the research will be 

covered. While PHS and USDA do not require dual review by both 

awardee and subcontractor IACUCs (i.e., only one of the assured 

IACUCs must review and approve the research), OLAW recommends 

the IACUC of the awardee institution have a mechanism for obtaining 

a copy of the performance site’s IACUC approval. Many times however, both IACUCs will elect to review the research as evidence of 

shared responsibility and to ensure the research will be conducted in 

compliance with their own institutional policies and practices in addi	

tion to meeting the federal laws and regulations. 

•
 If the awardee institution has a PHS Assurance, but the subcontractor 

or collaborating institution does not, the latter may be required to obtain 

one. The grant or contract may not be awarded until the Assurance is 

solicited by OLAW, submitted by the subcontractor, and approved by 

OLAW. The subcontractor must also submit the date of IACUC review. 

•
 If the awardee institution has a PHS Assurance but the subcontractor 

or collaborating institution does not, the latter may be brought under 

the awardee institution’s Assurance by an amendment to the Applica	

bility section of that Assurance. The IO signing the Assurance would 

then be responsible for the facilities and activities of the subcontrac	

tor, and the IACUC would be required to include relevant aspects of 

the subcontractor’s facility and program in its semi-annual program 

review. The subcontractor, in turn, would be required to recognize 

the authority of the IO and the IACUC of the awardee institution. Most 

awardee institutions do not elect this option. 
A.3. Operation and Administration 25 

•
 Another possible collaboration, that may or may not involve subcontracting, occurs if an awardee institution does not have an animal 

program or facility and is therefore not assured, but the investigator 

will use the facilities of an assured institution. Under these circum	

stances OLAW requires an “Interinstitutional Agreement Assurance” 

whereby both IOs agree that the project will be conducted in accor

dance with the assured institution’s Assurance and the investigator 

will abide by the determinations of the assured institution’s IACUC. 

The effect of such an agreement is to extend the IACUC’s oversight to 

include the particular project, and to meet the PHS Policy requirement 

that the grantee institution be assured. 

References 

Garnett, N.L., and W.R. DeHaven. Commentary: Protocol Review—Who’s to Blame? 

Lab Animal 28(7), 1999. 

NIH Guide for Grants and Contracts, Notice OD-01-017, February 12, 2001. 
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A.4. Training for Members 

For the IACUC to discharge its responsibilities a program of education and 

training is essential. A well-defined and implemented program, while prima	

rily directed to the IACUC member, would also be of value to researchers, 

administrators and others with responsibilities associated with research 

involving animals. 

It is the responsibility of the institution to provide suitable orientation, 

appropriate materials, adequate resources and training to enable IACUC 

members to carry out their duties consistent with the Guide, the PHS Policy 

and the Animal Welfare Regulations (AWRs). It is important to provide the 

tools necessary to assist members in understanding and evaluating issues 

that are brought before them. Appropriate training depends on the size, 

scope and needs of the research facility, but must incorporate the federal 

mandates of the IACUC. 

Local institutional policies and procedures need to be a part of the training 

and education program. Frequently, new members find it confusing to 

understand the differences between the federal policies and requirements 

and institutional policies and procedures. It is useful to provide an insti	

tutional policy manual as well as the Web sites for pertinent federal rules 

and regulations. 

Although the plan for training and education can take many different forms, 

a recommended syllabus with suggested topics for the orientation module 

and the continuing education module follows. 

In addition, ARENA sponsors a basic one-day training course for new IACUC 

members and persons with IACUC responsibilities – ARENA IACUC 

101 – and ARENA IACUC 101 “On the Road.” To learn more about this 

training program, contact the ARENA office at (617) 423-4112 or OLAW at 

(301) 496-7163, or visit the ARENA or OLAW Web sites (see Appendix A). 

27 
28 A. The IACUC 

Program of Education and Training for New IACUC Members 

Orientation Module 

(Suggested time – approximately 2 hours) 

Suggested Topics 

Objectives 

1. To introduce members to the role of the IACUC and its evolution2. To provide the basic information necessary for IACUC members todischarge their responsibilities3. To provide a forum for response to, and discussion of, members’­

concerns and questionsConducted by 

The IACUC staff, the IACUC Chair or designee, veterinary staff, or consult-­

ants. Training can be provided by one or more of these individuals.­

Syllabus 

1. The IACUC — its evolution and responsibilities1.1. Genesis and chronology1.2. U.S. Government Principles1.3. Benefits and pitfalls of IACUCs4.4. Criteria for membership4.5. Authority of the IACUC4.6. Unique role of the IACUC within the organization2. Operation and procedures2.1 Proposal (protocol) submission2.2 Proposal review2.2.1 Process2.2.2 IACUC review criteria2.2.3 Review by quorum2.2.4 Review by designated reviewers2.2.5 Post-meeting process2.3
 Monitoring of approved protocols2.3.1 Periodic review (continuing review)­
A.4. Training for Members 29 

2.3.2 Protocol changes (amendments) 

2.4 Records 

2.5
 Semiannual reviews 

2.5.1 Animal care and use program 

2.5.2 Institutional animal facilities 

2.6. Handling animal welfare concerns 

2.7. Roles, responsibilities, relationships 

2.7.1. IACUC 

2.7.2. IACUC Program office 

2.7.3. Veterinarian 

2.7.4.
 Animal Care Program (e.g., Department of Comparative 

Medicine or Laboratory Animal Resources) 

2.7.5. Institutional Official (IO) 

2.7.6. Office of Laboratory Animal Welfare (OLAW), NIH 

2.7.7. Animal and Plant Health Inspection Service (APHIS), USDA 

2.7.8. Project sponsor/grantor 

2.7.9. Community 

Suggested Resource Materials 

•
 Public Health Service Policy on Humane Care and Use of Laboratory 

Animals. NIH. Reprinted 2000. 

• Health Research Extension Act, P.L.99-158. 

•
 Animal Welfare Act – P.L. 89-544 as amended by P.L. 94-279, P.L. 

99-198, P.L. 91-579 and P.L. 101-624. 

• Animal Welfare Regulations. 9 CFR. 

• Institutional Administrator’s Guide for Animal Care and Use. NIH. 1988. 

• Guide for the Care and Use of Laboratory Animals. NRC. 1996. 

•
 ARENA/OLAW Institutional Animal Care and Use Committee Guidebook. 2002. 

• Institutional IACUC Policies and Procedures Manual. 

For additional suggestions see the Core Module in the National Research 

Council’s Education and Training in the Care and Use of Laboratory Animals 

– A Guide for Developing Institutional Programs, pages 11 through 15. 
30 A. The IACUC 

Program of Education and Training for IACUC Members 

Recommended Continuing Education Module 

(Varying amounts of time – can be incorporated in each IACUC meeting 

and/or designated or ad hoc meetings) 

Suggested Topics 

Objectives 

1. To increase members’ knowledge, understanding and awareness 

2. To keep members current on: 

2.1 Laws (federal, state, local) 

2.2 Regulations (proposed, promulgated/issued) 

2.3 Directives 

2.4 Guidelines 

2.5 Developments and trends 

2.6 Institutional policies 

3. To address issues, concerns and questions raised by IACUC mem	

bers, institutional staff, and the community. 

Conducted by 

The IACUC Staff, the Chair or designee, veterinary staff, or consultants. 

Syllabus 

Agenda based on: 

1. Questions and concerns brought to the attention of the IACUC 

1. Official directives 

3. Publications 

4. Notices of, and reports from, conferences, seminars, etc. 

5. Animal facility staff and/or veterinarian’s observations and recom	

mendations 

6. Facility inspections and program evaluations 

7. Problem situations 

Suggested Resources: See Appendix A. 
A.5. Legal Concerns 

The functions and activities of IACUCs are based on two federal laws: 

the Health Research Extension Act of 1985 (P.L.99-158) (HREA) and the 

1985 amendments to the Animal Welfare Act (AWA), the Improved Stan	

dards for Laboratory Animals Act of 1985 (P.L. 99-198). In addition, other 

federal rules may pertain to IACUCs, such as the Occupational Safety and 

Health Administration (OSHA), Food and Drug Administration (FDA), and 

Good Laboratory Practice (GLP) regulations, and the Endangered Species 

Act (ESA). Committee members need to be aware of the legal obligations 

of their institutions, the responsibilities of the IACUC in relation to these 

institutional commitments, and the regulatory requirements for which they 

may be personally accountable. 

Many states have statutes and regulations in place relevant to laboratory 

animals as well. Institutional Officials (IOs) and IACUC administrators should 

ensure that procedures are in place to enable IACUCs to be cognizant of 

and compliant with state and local laws and regulations that may affect 

their institution’s animal care and use program. A useful reference is the 

National Association for Biomedical Research (NABR) publication, State Laws 

Concerning the Use of Animals in Research. 

Institutions are responsible for informing IACUC members of their re

sponsibilities, providing training relative to their role on the IACUC, and 

ensuring that members have the information necessary to fulfill their duties 

as IACUC members: 

•
 IACUC members should be provided with documents such as the PHS 

Assurance with the Office of Laboratory Animal Welfare (OLAW), NIH, 

the PHS Policy, the Guide and the Animal Welfare Regulations (AWRs). 

Committee members should be aware of their institutional registration 

with the U.S. Department of Agriculture (USDA) and reports of inspec	

tions and other interactions with Animal and Plant Health Inspection 

Service (APHIS). 

•
 IACUC members should be free to request through the IACUC 

Chair or IO, guidance from the institution’s legal counsel with regard 

to Committee actions. 

•
 IACUC members should be provided with information regarding their 

obligation to treat material as privileged or confidential, especially prior 

31 
32 A. The IACUC 

to final Committee action, or agency funding. In the case of trade 

secrets or patent applications, such information is protected by law 

(7USC 2157, Section 27). 

•
 IACUC members should understand that their signatures are legally 

binding on official IACUC reports such as the six-month program 

review and facilities inspection report. 

Liability 

Under PHS Policy, the primary responsibility for meeting applicable federal 

and state rules rests with the research facility or PHS awardee institution. 

The IO is the individual held responsible on behalf of the research facility 

for ensuring compliance. Failure to comply with PHS Policy could result 

in OLAW’s withdrawal of approval of the institution’s Animal Welfare 

Assurance, thereby making the institution ineligible to receive funds for 

activities involving animals. 

Under applicable statutory provisions (7 U.S.C. Section 2149), the USDA 

has the authority to order a facility to cease and desist, and to impose a fine 

for noncompliance with the AWRs and AWA. The AWA provides for penalties of up to $2,500 per count and one year in prison, or both for violations 

of the AWRs. 

Freedom of Information 

The Freedom of Information Act (FOIA), 5.U.S.C.552, provides individ	

uals with a right to access to records in the possession of the federal 

government. The government may withhold information pursuant to the 

nine exemptions and three exclusions contained in the Act. 

The Electronic FOIA Amendments of 1996 (Public Law 104-231) amended 

the law in a number of ways that primarily address information systems, 

use of telecommunications, and electronic reading rooms. Most federal 

agencies provide guidelines for submitting FOIA requests through their 

agency Web sites. 
A.5. Legal Concerns 33 

Information about federally conducted or supported research projects, PHS 

Assurance documents, USDA annual reports filed by research facilities, and 

inspection reports of USDA, Environmental Protection Agency (EPA) and 

FDA, are generally available to the public under FOIA. 

Many states have public records laws and/or open meetings acts, known 

as “sunshine” laws, which may permit public access to information reviewed 

and generated by the IACUC, and public attendance at IACUC meetings. 

However, even in some “sunshine” law states, the IACUC, because it serves 

in an advisory capacity to the IO, may hold closed sessions. IACUC mem	

bers need to be aware of specific state laws regarding these issues and 

should always seek legal counsel if necessary to ensure compliance with 

applicable laws. 
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B. Oversight of the 

Animal Care and 

Use Program 

35­
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B.1. Program and Facility Review 

The PHS Policy and Animal Welfare Regulations (AWRs) stipulate that the 

IACUC must review the program for humane care and use of animals at 

least once every six months, using the Guide as the basis for evaluation for 

the PHS Policy and title 9, chapter I, subchapter A-Animal Welfare for the 

U.S. Department of Agriculture (USDA). Federal requirements also state that 

the IACUC must inspect all institutional animal facilities at least once every 

six months. 

Benefits of the Reviews 

•
 Reviews provide an ongoing mechanism for ensuring that the insti	

tution maintains compliance with applicable animal care and use 

policies, guidelines and laws. 

•
 Reviews serve as an opportunity for constructive interaction and 

education for the animal care personnel, research staff and IACUC 

members. 

•
 Reviews can help an institution prepare for subsequent visits by 

outside evaluators, such as USDA inspectors, Office of Laboratory 

Animal Welfare (OLAW) staff and Association for Assessment and 

Accreditation of Laboratory Animal Care International (AAALAC) 

site visitors. 

A summary of recurring IACUC issues related to semiannual program 

review and facility inspection identified by AAALAC during site visits is 

provided in Appendix C. 

Resources 

OLAW has developed a sample format for the program review and facility 

inspection that may be modified to meet the institution’s needs (see the 

OLAW Web site). The Table of Contents of the Guide or an institution’s 

AAALAC Program Description can also serve as an outline for the semiannual evaluation. 

37 
38 B. Oversight of the Animal Care and Use Program 

Conducting Program Evaluations 

Key aspects of an animal care and use program that should be emphasized 

in the semiannual evaluation include: 

•
 IACUC membership, functions and procedures, including protocol 

review (e.g., using page 10 of the Guide as a template, and PHS Policy 

IV.B. and C.); 

• facility inspection process; 

•
 provisions for reviewing and investigating concerns regarding animal 

care and use; 

• recordkeeping practices; 

• methods employed to meet reporting requirements; 

• occupational health and safety program; 

• veterinary medical care program; and 

• personnel qualifications and training. 

Specific procedures to accomplish program evaluation may include pre	

sentations by appropriate individuals (e.g., the veterinarian, an occupational 

health and safety representative, etc.) and review of written institutional 

policies such as standard operating procedures, guidelines on use of anes	

thetics and analgesics, and euthanasia procedures. Verifying conformance 

with the USDA Animal Care Policies (1999 et seq.) during the semiannual 

program review will help ensure that current practices are consistent with 

USDA regulatory interpretations. 

Facility Review 

All animal housing facilities must be inspected in the semiannual review, 

including: 

•
 satellite facilities (containment areas outside the central/core animal 

facility where animals are housed for more than 24 hours (PHS Policy), 

• areas in which surgical manipulations are performed (PHS Policy), 

•
 animal study areas (locations where USDA-covered species are held 

for more than 12 hours) (AWRs), and 

• holding facilities (AWRs). 

Laboratories in which routine procedures, such as immunization, dosing, 

and weighing, 
B.1. Program and Facility Review 39 

are conducted may be evaluated by other means such as random inspec	

tions. However, the institution, through its IACUC, is still responsible for all 

animal-related activities regardless of where animals are maintained or the 

duration of the housing. The IACUC must have reasonable access to these 

areas for the purpose of verifying that activities involving animals are being 

conducted in accordance with the proposal approved by the IACUC. 

Staffing and Scheduling the Facility Inspections 

The IACUC must conduct inspections of facilities at least once every six 

months. This may be accomplished by assigning specific facilities to subcommittees, which must consist of at least two IACUC members (AWRs). 

No IACUC member should be excluded should she or he wish to partici	

pate in an inspection. Ad hoc consultants may be used although the IACUC 

remains responsible for the evaluations and reports. The inspection team 

should have a working knowledge of the Guide and AWRs in order to fully 

evaluate the facilities that are being inspected. Section B.2. of this Guidebook also provides general guidance in this regard. 

Categories to be Inspected 

It is helpful for the inspection team to use a list of categories such as: 

• sanitation, 

• food and water provisions, 

• animal identification, 

• waste disposal, 

• animal health records, 

• controlled and/or expired drugs, 

• environmental control,­

• occupational health and safety concerns,­

• staff training, 

• knowledge of applicable rules and regulations, and 

• security. 
40 B. Oversight of the Animal Care and Use Program 

The IACUC may determine whether the supervisory personnel of various 

facilities should be notified of the date and time of an inspection. Advance 

notification allows individuals to be available to answer questions; an unex	

pected visit may show the facility during usual operations but also may 

result in a visit having to be rescheduled if key individuals are not available. 

Performing Inspections 

Adherence to the following recommendations will assist the IACUC in 

performing inspections: 

•
 An updated list of all facilities to be inspected should be maintained 

by the IACUC. 

•
 All proposals submitted to the IACUC should specify locations where 

animal procedures will be performed. 

•
 It is helpful to maintain a list of all facilities including room number, 

function of the room, species, and deficiencies identified during the 

previous inspection. 

• For satellite areas a contact person is useful. 

• For facilities with multiple rooms a floor plan can assist the inspectors. 

•
 If a subcommittee is performing the inspection, a blend of Committee members who last inspected the area with members who did 

not can bring both continuity and a fresh perspective to the inspec	

tion process. 

•
 Notes should be taken throughout the visit to assist in preparation of 

the final report. 

•
 Apparent deficiencies should be discussed with the person in charge 

of the facility to ensure that the team’s perception of the situation is 

accurate. In some cases an apparent deviation will be due to the 

experiment in progress, e.g., withholding of food prior to surgery. 

•
 Use of a checklist provides consistency and helps document that all 

categories were assessed. 

While the inspection of each facility must occur semiannually, there is no 

regulatory requirement that all facilities at an institution must be inspected 

at the same time (e.g., during the same month). Therefore, IACUCs at large 

institutions can stagger these inspections throughout the year, as long as 

each animal area is inspected at least every six months. 
B.1. Program and Facility Review 41 

Use of AAALAC Activities as Program Evaluation 

Provisions permitting use of ad hoc consultants may be invoked by IACUCs 

to make use of either of the two AAALAC assessment programs (Program Status Evaluation or Accreditation), or pre-assessment preparation 

activities, to meet the requirements for an IACUC semiannual program 

evaluation and subsequent report. In order to utilize one of these AAALAC 

related activities as a semiannual evaluation, the IACUC must ensure that 

the report complies with IV.B.3. of the PHS Policy, and officially endorse the 

report and submit it to the IO. If an institution is covered by the AWRs, the 

report must comply with §2.31(c) of the AWRs, at least two IACUC 

members must participate, no member wishing to participate may be 

excluded, and the report must be signed by a majority of the IACUC mem	

bers and include any minority views. 

Documentation 

A written report of the semiannual program review and facility inspection 

must be prepared. The AWRs require the report to be signed by a majority 

of the IACUC. The report must describe the institution’s adherence to the 

AWRs, the PHS Policy, and the Guide, and identify specifically any devia	

tions from these documents. 

Any deficiencies identified in these reviews must be designated by the IACUC 

as minor or significant. A significant deficiency is defined as a situation that 

is or may be a threat to animal health or safety. The IACUC, through the IO, 

must promptly report to OLAW any serious or continuing noncompliance 

with the PHS Policy or any serious deviation from the provisions of the 

Guide. For both categories of deficiencies, a reasonable and specific plan 

and schedule with dates for correction must be included in the final report. 

All individuals to be involved in the corrections should be consulted to 

ensure that the plan is realistic. If the institution is unable to meet the plan, 

the IACUC, through the IO, must inform Animal and Plant Health Inspection 

Service (APHIS) officials within fifteen business days of the lapsed deadline 

(AWRs). If the activity is federally funded, the relevant funding agency also 

must be informed. 
42 B. Oversight of the Animal Care and Use Program 

The report should indicate whether or not any minority views were filed, and 

minority views must be included in the final document. A copy of the report 

is sent to the IO and must be kept on file for a minimum of three years. It is 

often useful for the report to be delivered in person in order to emphasize 

the findings and plans for action. The institution must notify OLAW of the 

dates of the semiannual program evaluations and facility inspections in an 

annual report. 

References 

OPRR. 1991. The Public Health Service Responds to Commonly Asked Questions. 

ILAR News 33(4): 68-70. 

Potkay, S., N. Garnett, J. Miller, C. Pond, and D. Doyle. 1997. Frequently Asked 

Questions about the Public Health Service Policy on Humane Care and Use of Labo	

ratory Animals. Contemporary Topics 36(2): 47-50. 

NIH Guide for Grants and Contracts. December 12, 1999. Notice OD-00-007. 
B.2. Animal Environment, Housing and Management 

This section provides an overview of the IACUC’s role regarding animal 

environment, housing and management. The Guide provides recom	

mendations that are written in general terms and require the application of 

sound professional judgment (i.e., current best practices). The use of 

performance standards, or an outcome approach, will direct decisions to 

optimizing animal well-being while providing a refined animal model for 

the researcher. Variances from Guide recommendations in animal care and 

husbandry should be based on clear scientific justification, or rationale 

for an alternative approach to accomplish a performance based Guide stan	

dard, and must be approved by the IACUC. 

B.2.a. General 

The Guide states: 

Proper housing and management of animal facilities are 

essential to animal well-being, to the quality of research data 

and teaching or testing programs in which animals are used, 

and to the health and safety of personnel. A good man	

agement program provides the environment, housing, and 

care that permit animals to grow, mature, reproduce, and 

maintain good health; provides for their well-being; and 

minimizes variations that can affect research results. 

Specific operating practices depend on many factors that 

are peculiar to individual institutions and situations. Welltrained and motivated personnel can often ensure high quality 

animal care, even in institutions with less than optimal physi	

cal plants or equipment. 

Animals should be housed in a manner that facilitates the expression of 

species-typical behavior and minimizes stress-induced behaviors. For 

social species, housing systems should be designed to accommodate 

pair or group housing of animals. The Guide places responsibility with 

the IACUC for the review and approval of housing systems; it further 

recommends follow-up objective evaluations to ensure the housing system 

is appropriate for the health and well-being of the species and consistent 

with research objectives. 

43 
44 B. Oversight of the Animal Care and Use Program 

B.2.b. Animal Environment 

Housing 

Adequate animal husbandry practices and health maintenance are facili	

tated by well-constructed and maintained caging or housing systems. 

Cages should: 

•
 allow for conspecific social interaction within or between enclosures, 

adequate ventilation, and observation of animals with minimal dis	

turbance of them; 

•
 provide a safe and secure environment that permits the normal physi	

ologic and behavioral needs of the animals to be expressed; 

•
 enable ready access to food and water receptacles and be constructed 

of materials that balance the needs of the animal with sanitation; and 

•
 be constructed with materials that resist corrosion and withstand chipping, cracking or rusting. 

Unsealed wood may be acceptable for use as perches or other climbing 

structures, resting areas, or in the construction of perimeter fences, runs 

and pens, but wooden items need to be replaced periodically because of 

wear, damage, and to achieve adequate sanitization. 

Cage size requirements/recommendations for most common labora	

tory animal species are provided by the AWRs and the Guide. Cage 

complexities, vertical height of the cage, and the cage design can influence 

how an animal uses the cage space provided. The cage must provide 

sufficient space so that, at a minimum, the animal can turn around and 

express normal postural adjustments. The animal must have sufficient clean 

and unobstructed space to move and rest in. Use of wire bottom cages is 

discouraged for rodents, especially on long-term studies or in larger and 

older animals, as it may cause foot injury. Use of wire bottom cages should 

be scientifically justified and approved by the IACUC. 

Temperature, Ventilation, Illumination and Noise 

Environmental factors can have a profound effect on the health and 

well-being of animals as well as on the outcome of experimental manipula	

tion. Temperature, humidity, air pressure differential and air exchange rate, 

illumination level, and noise levels all may affect animal well-being and 

research results. 
B.2. Animal Environment, Housing and Management 45 

The range of daily temperature fluctuations should be kept to a minimum 

(e.g., ± 2o F) to avoid large demands on the animals’ metabolic and behav	

ioral processes. Relative humidity should also be controlled (e.g., 30% to 

70%). In general, an air exchange rate of 10 to 15 changes per hour is 

considered an acceptable standard. 

Light intensity, duration of exposure, wavelength of light, light history of the 

animal, pigmentation of the animal and other factors should be considered 

when establishing an illumination level in the animal room. 

Because sound exposure can have variable effects on animals, noise gen	

erators (e.g., human activities, noisy animals, equipment) should be mini	

mized in animal areas. Environments should be designed to accommodate 

animals that make noise, rather than resorting to methods of reducing the 

noise made by animals. 

A review of an animal care and use program should include consideration 

of environmental standards adopted for the facilities with adequate jus	

tification for deviations, which are reviewed and approved by the IACUC. 

While environmental control in outdoor facilities is much less stringent, 

acceptable ranges in temperature for several species are specified in the 

AWRs. Reliable methods for monitoring environmental control systems 

should be in place, including an after-hours monitoring and response 

program. Back-up heating, ventilation, air conditioning, and lighting sys	

tems are highly desirable. 

B.2.c. Husbandry 

Animal Identification 

It is imperative that research animals be adequately and appropriately 

identified and that records pertaining to individuals or groups of animals be 

maintained. A wide range of acceptable identification methods can be 

employed, including: 

• cage cards, 

• subcutaneous transponders, 

• ear notches and tags, 

• collars, 

• colored stains, and 

• individual animal tattoos. 
46 B. Oversight of the Animal Care and Use Program 

The use of toe-clipping to identify individual rodents is discouraged; when 

necessary, it should be rigorously justified for scientific necessity and done 

only on very young rodents. 

Animal records may consist of a cage card or may involve detailed indi	

vidual animal information, depending principally on the species and research 

requirements. Cage cards should include: 

• source of the animal, 

• strain or stock, 

• names and locations of responsible investigators, 

• pertinent dates, and 

• protocol number. 

Feeding 

All animals should receive food that is: 

• palatable, 

• free from contamination, and­

• of sufficient quantity and nutritive value to maintain their good health.­

Specific diets should be selected based on the needs of each species, with 

special consideration of the requirements for Vitamin C by guinea pigs and 

some species of nonhuman primates. Animals should be fed at least once 

a day except under conditions of hibernation, veterinary treatment, preprocedural fasts, or other justified circumstances. In some species and in 

some circumstances, varying the diet by providing “treats” can improve 

animal health and well-being. However, caution should be exercised that 

animals do not forsake eating their nutritionally balanced diet for treats. 

It is known that standard commercial dry bulk foods, when stored properly, 

retain their nutritional value for six months (generally three months for those 

containing Vitamin C, unless a stabilized form is used). 

To help ensure that fresh, uncontaminated food is provided: 

• bags should be stored off the floor, 

•
 the milling date should be known (the date or a code is usually stamped 

on each bag), and 

• the oldest stock should be used first. 
B.2. Animal Environment, Housing and Management 47 

Small quantities of food may be kept in animal rooms if stored in tightly 

covered, leak- and vermin-proof containers; these should not be moved 

from room to room. 

Food should be provided in receptacles that are accessible to all animals in 

a cage or pen and placed so as to minimize contamination. More than one 

receptacle may be necessary for some socially housed animals. Food 

receptacles should be easily cleaned and sanitized, and those functions 

should be performed on a schedule that meets Guide and AWR require	

ments. With limited exceptions, (e.g., neonatal animals or animals with 

limited mobility) food should not be placed on the bottom of the cage. 

Although some species may prefer this presentation, it results in waste 

and contamination of the food. 

Watering 

Potable drinking water should be available continuously or provided as 

often as necessary for the health and well-being of the animal, considering 

the animal’s species, age, condition, and any research requirements. Water 

may be provided in receptacles (e.g., bowls, bottles or via automatic water

ing systems). Whatever method is used, care should be taken to ensure 

that water does not become contaminated and is actually available. Water 

may be treated or purified to eliminate contaminants; however, some water 

treatments may cause physiologic changes, alter microflora, or affect ex	

perimental results. Sipper tubes and automatic watering devices should be 

checked daily for patency and cleanliness. Animals occasionally need to be 

trained to use automatic watering devices. Water bottles generally should 

be replaced and sanitized rather than refilled. 

Bedding 

Bedding may be used in the housing of a variety of commonly used laboratory animals. Bedding material should be absorbent and free of any 

substances that might harm the animals or alter research data. Cedar and 

untreated softwood products can affect an animal’s metabolism (e.g., liver 

enzymes), which may in turn affect immunologic or other physiologic 

parameters, and can increase the incidence of cancer. Bedding should be 

stored off the floor. 

Animals may be placed directly on bedding material, a common practice 

with many rodent species, or bedding may be placed under a slat-bottom 

cage. Bedding should be used in sufficient amounts and changed as 

often as necessary to keep the animals clean and dry and the animal room 
48 B. Oversight of the Animal Care and Use Program 

relatively odor free. Care should be taken to keep bedding from contacting 

water tubes as this may lead to leakage of water into the cage. The fre	

quency of bedding change depends on several factors, including the 

number of animals, species, type of caging, and type of bedding. 

B.2.d. Facility Maintenance 

Cleaning and Sanitation 

Cleanliness and sanitation are essential to the operation of an animal facil	

ity. The Guide and AWRs set forth recommended frequencies and methods 

for cleaning and sanitation of facilities, equipment and accessories. In gen	

eral, the frequency and methods should ensure that animals are maintained 

in a clean, dry environment, free from exposure to harmful contamination 

and excessive animal odors. Cleaning agents that mask animal odors should 

not be used as a substitute for good sanitation practices. Cleaning equip	

ment such as mops and buckets should not be moved from room to room 

due to the potential for cross-contamination. 

The most efficient and effective method of cleaning and sanitizing cages 

and accessories (e.g., feeders, water bottles, sipper tubes) is the use of 

a mechanical washing machine that provides rinse water temperature of 

at least 82.2oC (180oF) for a time adequate to achieve sanitization. Alternatively, portable high pressure spray washing and disinfection may be 

used. Least efficient and effective is hand washing and disinfection of such 

equipment. In general, enclosures and accessories (e.g., cage tops) should 

be sanitized at least every two weeks. Solid bottom cages, water bottles 

and sipper tubes should usually be sanitized weekly. The supply lines 

of automatic watering systems should be flushed and disinfected on a 

regular basis. 

Waste Disposal 

A research animal facility generates a significant amount of waste that must 

be removed and disposed of on a regular, frequent basis. Waste containers 

should be readily accessible throughout the facility and should be leakproof 

and equipped with tight-fitting lids. Disposal methods, including incin	

eration and removal to land-fill, must conform to federal, state and local 

requirements. Some jurisdictions consider all soiled animal bedding from a 

research facility to be “medical waste,” with consequently more stringent 

disposal requirements. 
B.2. Animal Environment, Housing and Management 49 

If waste must be stored while awaiting disposal, the storage area should be 

outside the animal holding and clean equipment areas. Animal carcasses 

and tissues require a separate cold storage area and regularly scheduled 

removal. Hazardous waste, including carcasses of animals exposed to 

radioactive or biohazardous agents, must be adequately sterilized and/ 

or contained prior to removal and disposal. 

Pest Control 

The research animal facility is an active place, with frequent movement of 

personnel, animals, equipment, containers, and food and bedding, creating 

ideal conditions for the introduction of pests, including arthropods, birds 

and wild rodents. Pest control programs are complicated by the potential 

for harm to animals and personnel, as well as interference with research 

data by many commonly used pesticides. A regularly scheduled, docu	

mented pest control and monitoring program should be implemented, which 

effectively combines elimination of all entry and harborage sites with good 

waste disposal and personnel training. If traps are used, methods should 

be humane. 

B.2.e. Emergency, Weekend and Holiday Care 

Laboratory animals must be observed by qualified personnel every day, 

including weekends and holidays to ensure their health and well-being, as 

well as to promote sound research practices. Skilled assistance, including 

veterinary care, must be readily available at all times. Names and telephone 

or pager numbers of those assigned these responsibilities should be promi	

nently displayed in the facility. A disaster plan should be part of the overall 

facility safety plan which takes into account both personnel and animals 

(see Section B.6.). 

B.2.f. Behavioral Management for Laboratory Animals 

There are varying requirements for attention to the behavioral management 

of laboratory animals, depending on the species of animal and the refer

ence document. 

The Guide provides recommendations for: 

• increasing the complexity of the structural environment, 

• addressing the social environment of animals, and 
50 B. Oversight of the Animal Care and Use Program 

•
 promoting the expression of species-typical activity in a cohesive 

behavioral management program for all vertebrate species. 

The AWRs require that research facilities develop, document and follow a 

plan for environment enhancement adequate to promote the psychological 

well-being of nonhuman primates. 

The plan must address: 

• the social needs of nonhuman primates; 

•
 environmental enrichment of the primary enclosure through provision 

of cage complexities, manipulanda, varied food items, foraging or taskoriented feeding methods, and safe personnel interaction; and 

•
 special needs of certain classes of primates (e.g., young animals, 

animals in psychological distress, some individually housed primates, 

and some great apes). 

Exemptions from some or all of the environment enhancement plan for 

scientific reasons must be documented in the protocol, approved by the 

IACUC, and re-reviewed not less than annually. The veterinarian may 

exempt individual primates from the plan. All exemptions must comply with 

the AWRs, Part 3, Subpart D, §3.81(e). 

The AWRs further require that research facilities develop, document and 

follow a plan for providing dogs with the opportunity for exercise. 

This plan must: 

•
 stipulate specific exercise opportunities for dogs housed individ	

ually as well as dogs housed in groups based on cage/pen/run 

floor space; and 

•
 identify the methods, frequency and duration of the opportunity 

for exercise. 

Provisions for exemptions from exercise may be made by the veterinarian 

in certain instances and the IACUC in others, and must be in accordance 

with the AWRs, Part 3, Subpart A, §3.8 (d). 
B.2. Animal Environment, Housing and Management 51 

Oversight 

The IACUC should provide oversight of the behavioral management program in a manner similar to its oversight of other husbandry components of 

the animal care and use program, and evaluate program outcomes during 

semiannual reviews. 

To adequately discharge this responsibility, the IACUC should have access 

to training or other orientation materials that will assist the IACUC members 

in evaluating the adequacy of the program (Bayne 2000). Formal, written 

plans for nonhuman primate environmental enrichment and canine exer

cise, established to provide a framework to the behavioral management 

program, should be approved by the IACUC and reviewed periodically. The 

committee should identify who is responsible for keeping the plan current 

and implementing the plan (e.g., an enrichment committee, the AV, etc.). 

The NRC publication, The Psychological Well-Being of Nonhuman Primates 

(1998), adopted by the Association for Assessment and Accreditation of 

Laboratory Animal Care International as a Reference Resource for accred	

ited institutions, advises a team approach to development and oversight of 

the behavioral management program to include investigators, veterinarians 

and the IACUC. 

References 

NRC. 1998. The Psychological Well-Being of Nonhuman Primates. National Acad	

emy Press, Washington, DC. 

Bayne, K. 2000. Laboratory animal enrichment. In: The IACUC Handbook 

(J. Silverman, M.A. Suckow and S. Murthy, eds.). CRC Press. New York. 
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B.3. Role of the Veterinarian 

Adequate veterinary medical care is an essential component of an animal 

care and use program and is required by the PHS Policy and Animal Welfare 

Regulations (AWRs). Institutions with smaller programs may opt for a 

part-time consulting veterinarian; the veterinarian’s overall responsibilities 

remain the same in all cases. 

It is the institution’s responsibility to support ongoing improvements in the 

animal care and use program through the development and implementation of procedures and policies (e.g., IACUC guidelines) that enhance the 

health of the animals (ACLAM 1996). Clear provisions should be made to 

give the veterinarian appropriate authority to execute a program of adequate 

veterinary care, including access to all animals. 

Qualifications 

The veterinarian participating in a laboratory animal care and use program must have training or experience in laboratory animal science and 

medicine, or in care of the species of animals maintained by the institution. 

Veterinarians can demonstrate the breadth and relevance of their expertise by achieving certification as a Diplomate of the American College of 

Laboratory Animal Medicine (ACLAM) or through other work experience 

and career accomplishments. Specialty training programs are available at a 

number of government, academic and commercial institutions to prepare graduate veterinarians to pursue ACLAM certification. Alternatively, 

veterinarians may qualify for ACLAM certification by working in a laboratory 

animal resource program and meeting other specified criteria. 

The veterinarian providing support to a laboratory animal care and use 

program must meet applicable state veterinary practice acts, inclusive of 

licensure requirements, particularly in the discharging of certain official 

duties, such as signing interstate health certificates or verifying rabies 

vaccination or tuberculosis status of animals. 

53 
54 B. Oversight of the Animal Care and Use Program 

Responsibilities 

The chief responsibility of the veterinarian is to provide for the health and 

welfare of animals. The Report of the American College of Laboratory 

Animal Medicine on Adequate Veterinary Care in Research, Testing and 

Teaching provides a detailed description of adequate veterinary care. 

The details of a veterinary care program will depend on the species of 

animals employed and the particulars of the laboratory animal use, but in 

all cases the program and care provided must comply with standard veterinary practice. 

The introduction of new animals is an important aspect of the veterinary care program with such considerations as stabilization periods, 

isolation and quarantine. Animals should be obtained only from licensed 

dealers or other legitimate sources. One of the prime mechanisms for 

ensuring high quality laboratory animals is to purchase them from commercial vendors who produce specific pathogen-free stock and maintain 

rigorous animal health monitoring programs to ensure quality. Generally, 

most animals are purpose-bred for laboratory use. Certain states have 

passed legislation requiring that cats and dogs used in research be bred 

specifically for that purpose. 

Random source or wild caught animals are not bred by the supplier (known 

as Class B dealers), but are obtained from a variety of sources including 

pounds, shelters or farms that may not conform to the same standards of 

animal husbandry and health as the research facility. Before their use, 

clinical evaluation and conditioning of these animals are required to ensure 

that they are not carrying diseases that can be transmitted to other animals, 

including humans, or do not introduce uncontrolled variables into research. 

Research facilities that obtain dogs and cats from sources other than dealers, exhibitors, and exempt persons must hold the animals for five full days, 

not including the day of acquisition, after acquiring the animal, excluding 

time in transit, before they may be used by the facility (9 CFR §2.38(j)). 

Research facilities must comply with the identification of animals requirements set forth in §2.38(g) during this period. 

Although selection of high-quality laboratory animals has reduced the prevalence of infectious diseases in research animal colonies, preventive 

medicine programs, conducted under the guidance of the veterinarian, continue to be important for maintenance of healthy animals. 
B.3. Role of the Veterinarian 55 

These programs include: 

• immunization against infectious pathogens; 

• surveillance of colonies for specific infectious microbial agents; 

• disease prophylaxis utilizing pharmaceutical agents; 

• isolation and quarantine of incoming animals; and 

•	 separate housing of animals according to species, source or different 

background microbial floras. 

While preventive medicine programs are successful in reducing the incidence of disease, illness and injury may still occur in laboratory animal 

colonies. The veterinarian is responsible for monitoring animal health, 

providing adequate diagnostic support through clinical assessments, laboratory diagnosis and necropsy when required, and treating animals when 

illness or injury necessitates veterinary medical care. Using a documented 

process, the veterinarian may delegate responsibility for care to trained 

technical staff but must always be available to provide rapid diagnosis 

and treatment. 

The AWRs stipulate that the veterinarian attend to not only the physical 

health of animals, but also the psychological well-being of nonhuman 

primates, and exercise for dogs. The plan for canine exercise must be 

approved by the Attending Veterinarian (AV) before it can be implemented. Additionally, animals that are exempted from either the canine exercise 

plan or the nonhuman primate psychological well-being enhancement plan 

for health, condition or behavioral reasons must be documented by the 

AV and, unless a permanent condition exists, reviewed by the AV every 

30 days. 

Specific areas requiring the veterinarian’s attention and guidance are: 

•	 the selection and utilization of suitable anesthetic and analgesic 

agents and methods of euthanasia; 

• appropriate selection of species for research projects; and 

•	 proper performance of surgical procedures and adequate preoperative, surgical, and post-operative care. 
56 B. Oversight of the Animal Care and Use Program 

The veterinarian should discuss with investigators the design and 

implementation of study proposals and may provide written guidelines 

dealing with these and other issues. Collegial exchanges between the 

investigator and the veterinarian before the submission of a proposal to 

the IACUC may address many of the Committee’s concerns and expedite 

the review process. 

At some institutions, the veterinarian or his/her staff may participate directly 

as a co-investigator in activities involving animals by providing clinical, 

surgical or other scientific or technical expertise to the study. Veterinarians 

sometimes also serve as principal investigators with responsibility for their 

own research and training programs. In such situations, the IACUC has the 

same obligation to review and approve the proposed activities as it would 

for any other investigator. When the veterinarian is personally involved in a 

research project, he/she must excuse himself/herself from the IACUC 

review and vote on the project. IACUCs may consider utilizing a consulting 

veterinarian to assist in review of such projects. 

The AWRs require institutions utilizing animals in research and teaching to 

provide training and instruction to personnel on humane methods of animal 

maintenance and experimentation. The veterinarian and the animal resource 

program staff, in conjunction with the IACUC, are usually responsible for 

providing such training. 

The PHS Policy requires institutional occupational health and safety programs to ensure that personnel who have laboratory animal contact 

are included in a risk assessment process and action plan that addresses 

workplace safety through appropriate educational, industrial hygiene and 

medical interventions. The veterinarian, in cooperation with appropriate 

health and safety officials at the institution, is often responsible for the implementation and execution of aspects of the program concerned with animal 

health and safety issues. 

The Veterinarian and the IACUC 

The veterinarian occupies an essential position on the IACUC with specific 

defined functions according to the PHS Policy and AWRs. Institutions employing several veterinarians may appoint more than one to the IACUC, but 

all institutions regardless of size must have at least one veterinarian with 

direct or delegated program authority and responsibility as a member of the 

IACUC. A strong veterinary presence on the IACUC has proven beneficial in 
B.3. Role of the Veterinarian 57 

many institutions. However, institutions should also be aware that the 

domination of IACUC activities by the veterinarian(s) may foster or be symptomatic of the disengagement of other members, thereby resulting in a less 

cohesive and effective IACUC. 

The veterinarian should keep abreast of current literature on comparative 

medicine and laboratory animal science. The knowledge gained often leads 

to suggestions for alternative techniques, models or species that may 

enhance animal well-being, augment the study design and help ensure the 

completion of the proposed study. 

Reference 

American College of Laboratory Animal Medicine. 1996. Report of the American 

College of Laboratory Animal Medicine on Adequate Veterinary Care in Research, 

Testing and Teaching. 
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B.4. Occupational Health and Safety 

The health and safety of individuals working in animal care and use 

programs is an area of institutional concern requiring commitment from 

the senior officials of the institution. The goal of the occupational health and 

safety program (OHSP) is to prevent occupational injury and illness by avoiding, controlling or eliminating hazards in the workplace. The emphasis of 

such a program is the prevention of illness and injury, but it also includes 

provisions for early diagnosis and treatment when necessary. 

The IACUC’s Responsibility for Occupational Health and Safety 

The PHS Policy places responsibility for ensuring a safe working environment for personnel involved in the animal care and use program with the 

institution. An effective OHSP interdigitates with many separate institutional 

components including animal care and use, research, environmental health 

and safety, occupational health, and administration and management. A 

natural point of convergence for these functionally distinct institutional 

elements at many institutions is the IACUC. Assurance of a safe working 

environment is one of the topics the IACUC should consider in each animal 

use proposal and as part of the semiannual program evaluation. It is generally necessary to involve health and safety specialists in the design and 

implementation of the IACUC review guidelines. 

Role of the IACUC in the Occupational Health and Safety Program 

Procedures should be developed for conducting a health and safety review 

of research activities that present hazards. These procedures should be 

incorporated into the IACUC protocol review process. Procedures to 

identify and address non-experimental hazards (e.g., during semiannual 

facility inspections and program reviews) should also be implemented. 

Communication and other procedural links between the IACUC and the 

environmental health and safety professional or office should be established, 

maintained and documented. In some institutions, IACUCs defer review of 

OHSP to an office of health and safety review. 

59 
60 B. Oversight of the Animal Care and Use Program 

The IACUC also has a role in ensuring that personnel comply with health 

and safety requirements (e.g., ensuring personnel have received appropriate training, evaluating compliance with standard operating procedures or 

institutional policy during semiannual facility inspections, etc.). 

Elements of an Occupational Health and Safety Program 

An effective program design requires input from health and safety specialists and will include the following elements: 

• administrative procedures, 

• facility design and operation, 

• risk assessment, 

• exposure control, 

• education and training, 

• occupational health-care services, 

• personal protective equipment, 

• equipment performance, 

• information management, 

• emergency procedures, and 

• program evaluation. 

The details of each element will be dictated by the extent and nature of 

employees’ exposure and the type of animal use program. 

Personnel Participation in the Occupational Health and Safety Program 

A wide range of personnel (e.g., animal care staff, investigators, technical 

staff, students, volunteers, engineers, housekeepers, security officers, and 

maintenance personnel who care for or use animals, their tissues or fluids, 

or who may be exposed to them as a consequence of their job) should be 

provided the opportunity to participate in the OHSP. 

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

based on risk assessment, including: 

• hazards posed by the animals and materials used; 

• exposure intensity, duration, and frequency; 
B.4. Occupational Health and Safety 61 

• susceptibility of personnel; and 

• history of occupational illness and injury in the workplace. 

Health and safety specialists should be involved in the assessment of risks 

associated with hazardous activities. 

Education and Training 

There are ethical and legal requirements to inform individuals of health risks 

that affect them and appropriate precautions. The objectives of an 

institution’s OHSP can be achieved only if employees are appropriately 

trained to understand the hazards associated with their work area and job 

duties, and how those risks are mitigated through institutional policies, 

engineering controls, work practices, and personal protective equipment. 

Training should include information about: 

• zoonoses, 

• chemical safety, 

• microbiologic and physical hazards (e.g., allergens, radiation), 

• hazards associated with experimental procedures, 

• handling of waste materials, and 

• personal hygiene. 

Proficiency in work assignments through education and training will also 

contribute to a safer work environment. Training should be a continuous 

process, and records of OHSP training of personnel should be maintained. 

Preventive Medicine and Provision of Medical Care 

The principal means of preventing occupationally acquired illness or injury 

is by controlling or eliminating hazards. The efficacy of the prevention 

program will depend on the institution’s resource allocation to hazard 

control and the cooperation or compliance of personnel who are potentially at risk. The quality of the preventive medicine program can also be 

increased if its development and implementation involves input from trained 

health professionals. 
62 B. Oversight of the Animal Care and Use Program 

In addition to established mechanisms for reporting and treating accidents 

and injuries, the institution should have access to medical expertise in 

zoonotic diseases and other health risks associated with laboratory animal 

care. Good communication with medical staff will also facilitate better management of the health of animal care personnel and minimize repeat injuries 

and infections. 

Specific Medical Concerns for Individuals Working in the 

Animal Research Environment 

The complexity of the animal research environment creates numerous classes 

of hazards. 

Physical hazards include: 

• animal bites, scratches, and kicks; 

• sharps; 

• flammable materials; 

• high pressure containers and equipment; 

• low or single color lighting in animal rooms resulting in poor visibility; 

• electric hazards, particularly in areas of water usage; 

• ultraviolet and ionizing radiation; 

• lasers used in surgical areas; 

• inadequate housekeeping practices; 

• ergonomic demands; 

• machinery; and 

• noise. 

Chemical hazards result from their flammable, corrosive, reactive, explosive or toxic properties. Burns and irritation of the skin are the most 

common chemical injuries related to animal care and use. 

Allergic reactions to animals, occasionally resulting in the development of 

occupation-related asthma, are among the most common conditions that 

adversely affect the health of personnel in the animal research environment. 

Estimates of the prevalence of allergies in animal care workers range from 

10% to 44%. Preplacement screening evaluations, attention to facility 

design, work practices, and the use of personal protective equipment can 
B.4. Occupational Health and Safety 63 

reduce the potential development of laboratory animal allergy and possibly 

alter its severity. 

Infectious diseases also pose a significant risk depending on the species 

and health status of animals involved and the level of exposure to them by 

animal care personnel. 

Infectious diseases to which animal care personnel may be exposed include: 

•	 viral infections, such as contagious ecthyma, the hepatitides, and 

Cercopithecine herpes virus 1 (Herpes B); 

• rickettisal diseases, such as Q fever and cat scratch fever; 

• bacterial diseases, such as tuberculosis, salmonellosis, and shigellosis; 

•	 protozoal diseases, such as toxoplasmosis, giardiasis, and cryptosporidiosis; and 

• fungal diseases, such as dermatomycosis. 

In addition to infections acquired from live animals, animal tissues and 

excreta can serve as sources of zoonoses. Careful monitoring and quarantine of any animals with potential viral or bacterial infections or parasitic 

infestations are crucial components of any animal care and use program. It 

is important to immunize animal care personnel against tetanus. Routine 

tuberculosis testing is essential and measles vaccination may also be 

appropriate for workers exposed to nonhuman primates. 

Common Occupational Health and Safety Program-wide Pitfalls* 

•	 Instead of being based on hazard identification and risk assessment, the program identifies personnel risk based on animal contact 

time or frequency. 

•	 There is inadequate training on occupational health and safety topics 

(e.g., zoonoses, allergies). 

•	 Not all personnel at risk (e.g., students, visiting scientists) are offered 

inclusion in the program. 

•	 Hazard identification covers experimental hazards, but does not 

address hazards intrinsic to animal care and use. 

•	 There is inadequate linkage between the IACUC and the institutional 

safety committee(s). 

*From data collected by AAALAC International. 
64 B. Oversight of the Animal Care and Use Program 

References 

CDC/NIH. 1999. Biosafety in Microbiological and Biomedical Laboratories, 4th Edition. U.S. Government Printing Office, Washington, DC. 

Holmes, G.P. et al. 1995. Guidelines for the prevention and treatment of B-virus 

infections in exposed persons. Clin Infect Dis 20:421-439. 

National Research Council. 1997. Occupational Health and Safety in the Care and 

Use of Research Animals. National Academy Press, Washington, DC. 

Preventing Asthma in Animal Handlers. 1998. NIOSH/DHHS, Cincinnati, OH. 

Criteria for a recommended standard occupational exposure to waste anesthetic 

gases and vapors. March 1977. DHEW Pub. No. (NIOSH) 77-140. 

Occupational Health and Safety Administration Standards 29 CFR 1910.1030. 

Bloodborne pathogens. 

Occupational Health and Safety Administration Standards 29 CFR 1910.1450. 

Occupational exposure to hazardous chemicals in laboratories. 

Hollander, A., G. Doekes, and D. Heederik. 1996. Cat and dog allergy and total IgE 

as risk factors for laboratory animal allergy. J Allergy Clin Immunol 98:545-554. 

Knysak, D. 1989. Animal aeroallergens. Immunol Allergy Clin No Amer 9:357-364. 
B.5. Personnel Training and Education 

All staff working with laboratory animals must be qualified to do so in 

order to ensure the humane treatment of animals. Training is a classic 

performance standard where the emphasis is on the outcome (i.e., all 

personnel qualified to do their jobs). Although the PHS Policy and Animal 

Welfare Regulations (AWRs) do not specify a particular program or the 

frequency with which a program should be offered, the requirement for 

competence is mandatory. 

The AWRs, in Sec. 2.32 (a) and (b), specify: 

It shall be the responsibility of the research facility to ensure 

that all scientists, research technicians, animal technicians, 

and other personnel involved in animal care, treatment, and 

use are qualified to perform their duties. This responsibility 

shall be fulfilled in part through the provision of training and 

instruction to those personnel. Training and instruction shall 

be made available, and the qualifications of personnel 

reviewed, with sufficient frequency to fulfill the research 

facility’s responsibilities.... 

The PHS Policy, Section IV.C.1.f. places responsibility specifically with the 

IACUC to ensure that personnel conducting procedures on research 

animals are appropriately qualified and trained in those procedures. 

Personnel training in the care and use of research animals is an important 

aspect of the alternatives concept (replacement, reduction and refinement) 

described in Section C.2.a. Training in the recognition and alleviation of 

animal pain, distress, and abnormalities addresses refinement. Similarly, 

training in the conduct of animal procedures prepares staff to work without 

causing unnecessary harm to the animal. Technical proficiency also invokes 

reduction by avoiding wasted animal lives through failed procedures. 

Personnel training should be seen as one of the pillars supporting the 

animal research program. Training of staff is essential for safeguarding the 

quality of the animals as a tool of research or testing. A lack of training may 

65 
66 B. Oversight of the Animal Care and Use Program 

result in inadequate husbandry and poor peri-procedural care, which can 

undermine the physiological status of the animal thereby potentially impairing the integrity of research results. 

Who Should Receive Training? 

All staff should receive training if they interact directly with or work in the 

vicinity of animals. Training made available for each type of staff should be 

specific to the animal species involved and to the kind of procedures to be 

performed or animal-related interactions. 

For training purposes, staff can be grouped as: 

• researchers, 

• animal care technicians, and 

• other (e.g., maintenance or support staff). 

In some institutions, staff may not be clearly divisible into these groups if 

job responsibilities are more diversified than this classification suggests. 

For example, facility staff such as animal health technicians may have job 

functions that include both animal care and research procedures. 

Training should also be made available to temporary staff, such as students 

and visiting scientists. These groups may be difficult to intercept for training 

unless there is a way to identify them. 

Development of a Training Program 

A training program should meet the needs of each type of staff, as 

described above, who work with or around laboratory animals. There are 

many training resources and methodologies that can be used in the 

development of a training program: courses, seminars, one-on-one training, conferences, computer-based media and videotapes. When appropriate for the job responsibilities, technicians should be encouraged to 

pursue certification by professional associations, such as technician certification by the American Association for Laboratory Animal Science and 

the Academy of Surgical Research. 
B.5. Personnel Training and Education 67 

All staff should have exposure through training to regulatory requirements 

for animal welfare and occupational health and safety considerations. Staff 

who work directly with animals should have training that supports the 

humane care and use of animals in the course of day-to-day procedures. 

The AWRs, in Sec. 2.32 (c), require that training and instruction of personnel 

must include guidance in at least the following areas: 

(1) Humane methods of animal maintenance and experimentation, including: 

(i) The basic needs of each species of animal; 

(ii)	 Proper handling and care for the various species of animals used 

by the facility; 

(iii) Proper pre-procedural and post-procedural care of animals; and 

(iv) Aseptic surgical methods and procedures; 

(2)The concept, availability, and use of research or testing methods that 

limit the use of animals or minimize animal distress; 

(3)Proper use of anesthetics, analgesics, and tranquilizers for any species of animals used by the facility; 

(4)Methods whereby deficiencies in animal care and treatment are reported, including deficiencies in animal care and treatment reported 

by any employee of the facility. 

(5)Utilization of services (e.g., National Agricultural Library, National 

Library of Medicine) available to provide information: 

(i) On appropriate methods of animal care and use; 

(ii) On alternatives to the use of live animals in research; 

(iii)	 That could prevent unintended and unnecessary duplication of 

research involving animals; and 

(iv) Regarding the intent and requirements of the [Animal Welfare] Act. 

Training programs should also include information on occupational health 

and safety. Specific recommendations for general training objectives 

may be obtained from Education and Training in the Care and Use of 

Laboratory Animals: A Guide for Developing Institutional Programs. 

Recommendations for general training objectives are outlined in Table A 

for each type of staff. 
68 B. Oversight of the Animal Care and Use Program 

B.5. Table A. General Training Objectives 

Animal Care Research Other 

Topics Personnel Personnel Personnel 

Animal welfare laws, regulations, 

policies, and guidelines 

All animals are to be on a protocol 

Cage card information 

How to report perceived deficiencies 

in animal care and use 

Recognizing pain and distress 

Alleviating pain and distress 

PI’s responsibilities 

Protocol requirements 

Role of the IACUC 

Animal related hazards 

Facility hazards 

Occupational health and 

safety concerns 

Behavior and appearance 

of healthy animals 

Proper use of cage 

wash equipment 

Assure qualifications 

of research staff 

Humane techniques for 

animal procedures 
B.5. Personnel Training and Education 69 

Personnel Training Records and Documentation 

Although there is no specific requirement to document individual training 

activities, training records demonstrate that staff have met the training 

requirements related to their responsibilities in the research animal program, 

and regulatory or other oversight authorities often request to inspect 

personnel training records as evidence of an effective program. 

Training records have value in tracking the range of topics offered, the 

frequency of training sessions, and the participation of institutional staff. 

Such records may include training received in informal settings, e.g., oneon-one instruction, common for teaching animal use methodologies. 

Training records may be archived with the IACUC, a training coordinator, 

research departments or individual laboratories. Whatever the location, training records should be accessible to inspection by any oversight authority, 

including the IACUC. If training records of research staff are stored in laboratories, a good practice would be to include a brief review of training records 

among the objectives for the IACUC’s semiannual inspection of facilities. 

Training Personnel 

Many institutions with a large research program have a training coordinator 

to oversee the training program for all personnel with animal care and use 

training needs. The training coordinator should be involved in IACUC meetings when institutional training issues are discussed. 

Training coordinators should not be the only ones with training responsibilities. The facility staff, (e.g. veterinarians, veterinary technicians, facility 

managers and animal care technicians), also should be involved in training 

activities to the greatest extent possible. Their training activities, either with 

individuals or groups, should be acknowledged as a valuable contribution 

to the animal research program. In this way, individual expertise is fully 

utilized and every contact with facility staff offers a training opportunity. 

In addition, other staff or outside consultants with specialized expertise can 

be incorporated into the training program. For example, occupational health 

professionals may be invited to take part in training on safety related 

issues. Training in specialized animal methodologies may be best performed by researchers who are accomplished in these techniques. Training 

program staff, if available, should participate in or oversee the training by 

outside experts to ensure that the training content is appropriate. 
70 B. Oversight of the Animal Care and Use Program 

Institutional Support of Training 

A high level of staff participation in a training program is essential for achieving 

the performance standard of staff qualifications necessary for quality 

research and expected by regulatory authorities. Institutions with mandatory training programs often have the most uniform results. 

When training is not mandatory, there is much that an institution can do to 

encourage participation in the training program. When senior management 

and IACUC members take part in formal training programs, (e.g., on 

compliance issues), staff recognize an imperative to attend these sessions. The involvement of outside speakers with recognized expertise is 

often successful to draw larger groups to a training session. Letters urging 

staff participation in training programs are effective when sent by senior 

administrators and the IACUC to department chairpersons and principal investigators. 

Methods that increase awareness and availability of information within the 

institution are valuable to support a training program. A combination of a 

training manual, newsletters, mailings, posted flyers, brochures and a Web 

site inform staff about the requirements for training, the institution’s animal 

welfare standards, and the services available in the training program. 

References 

Russell, W. M. S. and R. L. Burch. 1959. The Principles of Humane Experimental 

Techniques. Methuen & Co., London. (Reprinted as a Special Edition in 1992 by the 

Universities Federation for Animal Welfare.) 

NRC (National Research Council). 1991. Education and Training in the Care and Use 

of Laboratory Animals: A Guide for Developing Institutional Programs. A report of 

the Institute of Laboratory Animal Resources Committee on Educational Programs 

in Laboratory Animal Science. National Academy Press, Washington, DC. 
B.6. Emergency Preparedness 

B.6.a. Security and Crisis Management 

Anti-animal research activities during the past several years against institutions using animals in research, testing and teaching programs have 

included demonstrations, break-ins, vandalism, life threats and harassment 

by mail or telephone, arson, and bomb threats. Since the IACUC has 

responsibility for the welfare of animals at its facility, it shares responsibility 

for the security of the animals and personnel who care for and use these 

animals with other units within the institution, such as the units responsible 

for security, public information, and governmental relations. Institutions 

receiving federal funds have an obligation to protect the federal investment 

in research by exercising due diligence in this area. The IACUC can serve a 

key role in advising the IO and the institution of potential risks and vulnerabilities, and in developing a plan for responding to potential or real threats. 

In all cases the IACUC must consider allegations of noncompliance or 

animal welfare issues as concerns that must be addressed in accordance 

with relevant PHS Policy provisions and Animal Welfare Regulations (AWRs) 

(see Section D). 

There are four key elements to an institution’s preparedness: 

• an animal care and use program of impeccable integrity; 

• a security program based on risk assessment; 

•	 an integrated communication plan with descriptions of research 

projects in lay terminology, spokespersons and a telephone tree; and 

•	 an internal and external community outreach program that includes 

legislators and funding agencies. 

Crisis Management Team 

The establishment of a crisis management team before a crisis occurs is 

important in order to respond in a timely manner. This team may be 

comprised of individuals representing the following areas: security, public 

information, laboratory animal resources, the IACUC, management/research 

administration (including the IO), legal affairs, and governmental relations. It 

71 
72 B. Oversight of the Animal Care and Use Program 

is helpful for this team to meet periodically to keep abreast of current issues 

at the national and local level, and to be apprised of current research activities. 

Risk Assessment – Security 

The first step in developing a security program is to conduct a risk assessment of the institution’s facilities, and evaluation of the existing security 

system. Organization of a security and communication plan then follow. 

Some key points include: 

1. Determine facility vulnerability. 

a. Look at the research facilities with a “public eye.” 

b.	 Be aware that use of certain animal species can increase vulnerability (e.g., nonhuman primates, cats and dogs). 

c.	 Be aware that some kinds of research may be perceived to be 

controversial (e.g., surgical and neuroscience protocols, including drug-addiction studies). 

d. Carefully review protocols that are more likely to generate requests 

for information under state or federal open records laws, such as 

items (b) and (c) above. 

2. Evaluate the security system. 

a. Review policies regarding access and electronic surveillance systems. 

b.	 Check location of keys and access to animal rooms; entrances 

and exit sites such as stairwells and roof access. 

c. Determine who has access to buildings during nights and weekends. 

d.	 Ensure computer security, network access, etc. with computer 

administrators. 

3. Check storage of research data. 

a.	 Ensure security of IACUC records and research data, including 

copies maintained offsite. 

b. Review research protocols for confidential information. 

c. Review protocols for graphic and/or sensitive terminology. 

4. Organize a security plan. 

a. Consult with local police to establish procedures. 

b. Establish clear lines of authority and roles in a crisis situation. 

c. Maintain a list of research projects and scientists. 
B.6. Emergency Preparedness 73 

d. Identify ongoing investigations by regulatory agencies. 

e. Limit access of delivery persons within animal care facilities. 

f. Keep duplicate physical layout plans available off site. 

g.	 Share information with security personnel about activism at other 

research organizations. 

h.	 Develop a document that will provide pertinent information to the 

police in the event of an incident such as type of incident, location, animals or property destroyed or stolen, people involved, 

time, method of entry, and need to check for hazardous materials. 

5. Organize a communication plan in the event of an incident during the 

day, after hours, weekends and holidays. 

Communications and Risk Reduction 

Institutions using animals need to communicate effectively and on an 

ongoing basis with the internal and external community and the media. It is 

important to build these relationships over time and to keep individuals in 

all of these areas informed about the significance of the work in which 

animals are used, and the institution’s commitment to scientific standards 

through quality animal care and use. Being proactive by conveying significant advances in research using animals ethically and humanely can 

reduce the potential for negative public reactions in a crisis situation. 

The IACUC Chair and members can interact with institutional public information officers, researchers, veterinarians, technicians and the research 

administration to identify spokespersons to address animal research issues. 

These spokespersons should be provided adequate training. Fact sheets 

should be readily available about the institution’s policies and commitment 

to humane and appropriate animal care and use, the quality of its animal 

care and use program (including accreditation), and brief summaries of the 

value and importance of any specific animal use under scrutiny. Written 

materials need to be written in language understandable to nonscientists. 

Institutions must be prepared to respond to allegations honestly (i.e., if real 

noncompliance with relevant policies or regulations is substantiated then 

the institution must take appropriate action and should be forthcoming about 

the situation). 

In the event of a crisis the facility that is prepared can respond quickly through 

its spokespersons with accurate and factual information. It is also important for the institution to notify OLAW in such an event so they can confirm 
74 B. Oversight of the Animal Care and Use Program 

the status of the institution’s PHS Assurance and any PHS support, as 

well as AAALAC, which maintains a crisis communication plan to assist 

accredited institutions. 

Maintaining a high quality animal care and use program, good relationships 

within the institution and the community, and an effective education 

program can help to prevent and alleviate many crisis situations and significantly reduce the need for long term damage control. 

References 

CBRA Crisis and Communications Manual, California Biomedical Research Association. April 2000. 

Institutional Administrator’s Manual for Laboratory Animal Care and Use. PHS. NIH 

Publication #88-2959. 

B.6.b. Disaster Planning 

As a fundamental component of the operational plans for most animal 

facilities, the Disaster Plan is a detailed, site-specific compilation of critical 

resources that are helpful in a variety of crisis events. The Guide recommends that all animal facilities have a Disaster Plan as part of their overall 

program and that the veterinarian or animal facility manager be part of 

the official institutional response team. While the Guide does not outline 

the elements of a Disaster Plan, it does suggest that facilities maintain 

sufficient emergency power necessary to maintain critical services (e.g., 

heating, ventilation and air conditioning (HVAC) system) and support functions (e.g., freezers, ventilated racks, isolators). Unique components 

of the facility may require special considerations. The proper institutional 

authority should approve the final plan so that appropriate resources can 

be committed during an emergency event. Typically, the IACUC does not 

have primary responsibility for emergency preparedness, but because 

emergency events could have significant impact on animals and the animal 

facility, the committee may choose to assess their site’s preparedness 

during regular semiannual program reviews. 

Emergency Management 

In addition to the development of a Disaster Plan, an animal facility should 

consider approaching disaster preparedness from the more encompassing 

perspective of emergency management. One invaluable resource for emergency management information is the Federal Emergency Management 
B.6. Emergency Preparedness 75 

Agency (FEMA). FEMA is an independent federal agency founded in 1979 

that reports directly to the President. FEMA’s mission is to reduce loss of 

life and property and protect our nation’s critical infrastructure from all types 

of hazards through a comprehensive, risk-based, emergency management 

program. FEMA considers an effective emergency management program 

to consist of four parts: 

•	 Mitigation (activities related to preventing future emergencies or 

minimizing the effects of emergencies that occur); 

•	 Preparedness (incorporation of the planning and preparations required to handle an emergency, including the Disaster Plan); 

•	 Response (the Disaster Plan put into action when an emergency 

occurs); and 

•	 Recovery (the actions needed to return to normal after an emergency 

occurs.) 

Segments of a Disaster Plan 

This section focuses on the Disaster Plan because it is the component of an 

emergency management program that the IACUC should review as a part 

of its semiannual program review. The content and scope of the Disaster 

Plan will be shaped and determined by the individual program and facility. 

The following approach is one way to create a Disaster Plan and can be 

useful to the IACUC in evaluating the facility’s plan. 

A suggested organization method includes: 

• developing a planning team, 

• defining emergencies, 

• identifying critical functions and systems, 

• defining resources and contacts, 

• developing policies and procedures, and 

• training staff and testing emergency equipment. 

Developing a Planning Team 

The Disaster Plan is best completed by the group of individuals that would 

respond to an emergency. The emergency response planning team should 

be comprised of individuals of various backgrounds and expertise, including certain animal facility staff and investigators, as well as representatives 
76 B. Oversight of the Animal Care and Use Program 

from the facility engineering/maintenance group, security, occupational 

health services, safety, public relations and risk management. Due to sitespecific variables such as the type of facility, hazards, risks and available 

resources, teams will be as unique as the plan. One of the early actions of 

the team should be to define its mission, goals and methods of operation. 

The team will also need to enlist project support from senior management 

so that resources are allocated for implementation of prescribed action plans. 

Ultimately, they will also need to integrate the facility Disaster Plan with any 

site-wide or local Disaster Plans. 

Defining Emergencies 

FEMA and other emergency management organizations have described 

various scoring methodologies to help categorize and rank emergencies. 

They generally divide emergencies (hazards) into three different categories: 

• natural emergencies, 

• technical emergencies, and 

• civil emergencies. 

Natural emergencies are the most commonly occurring “disasters” and 

include weather, seismic or ocean related events. Examples include 

tornadoes, hurricanes, floods, earthquakes, flood tides, etc. Technical 

emergencies are mechanical or human failures and include HVAC failures, 

computer system failures, chemical spills and structural failures. Civil 

emergencies are deliberate human events such as terrorist attacks, sabotage and labor strikes. 

When developing a Disaster Plan, it may be helpful to list each type of emergency and include the primary and secondary effects. Secondary effects 

can greatly complicate a problem and can affect some critical functions 

even more than the primary. To help in planning, the list should include the 

probability of an event occurring (see Table A). The Disaster Plan should be 

sufficiently general to be responsive to unplanned types of crises. 

As a planning exercise in evaluating primary and secondary effects, consider the scenario of a typical, midwinter moderately severe snowstorm, 

which can present multiple problems. Snow can clog the air intake filters 

and interfere with the HVAC system, or affect the electrical supply. Snow 

can contribute to local flooding when it melts. Either snow or flooding may 

affect employees’ ability to get to work or prevent essential deliveries from 
B.6. Emergency Preparedness 77 

being made. If electrical power is lost, and the facility is relying on emergency back-up generators, there may be refueling problems when the fuel 

reserves are exhausted and delivery trucks can’t reach the site. This 

example shows how the planning exercise can provide valuable modeling 

information useful in disaster preparation. 

Identifying Critical Functions and Systems 

Fundamentally, the Disaster Plan should address ways to maintain or cope 

with the loss of critical functions and systems in the animal facility. To do 

this, it is important to rigorously identify all critical animal facility specific 

functions and systems. The critical functions and systems fall into two 

general categories: mechanical systems and personnel functions (see Table 

B). It is helpful to compare the list of primary and secondary effects of 

the different emergencies (Table A) and review their impact on the critical 

functions and systems. Different scenarios can become the basis for action 

plans and preparedness activities. 

Defining Resources and Contacts 

The Disaster Plan can also include lists of available resources and contacts 

to be used during emergency events. The lists can include various emergency equipment, spare parts, equipment capacities, levels of redundancy 

built into the mechanical equipment systems and ways to put the equipment into use. Additionally, this section might include critical vendors that 

can supply services during an emergency, such as a supplier to perform 

periodic refueling of emergency generator fuel tanks, as well as up to date 

emergency personnel notification lists, including criteria for contacting 

specific individuals. More advanced plans stage the level of an emergency 

and clearly prescribe the type of response for each level. Other pertinent 

items such as floor layouts, mechanical equipment plans, the names and 

numbers of national, regional and local emergency response organizations 

(FEMA, Red Cross, Police, etc.) and local weather information resources, 

can be included. 

Developing Policies and Procedures 

The core elements of a Disaster Plan are the policies, guidelines and procedures that are put into action during an emergency. The plan should 

address very specific emergencies and/or give general outlines for action 

steps in response to an emergency. Many plans will also focus on coping 
78 B. Oversight of the Animal Care and Use Program 

with the loss of a critical function or system. This approach is best when it 

includes evaluation of the reliability of the back-up systems affected during 

a complex emergency situation. Available resources should be clearly identified and information on how to access the resources included. Clear lines 

of authority and responsibility should be established and documented. 

Training Staff and Testing Emergency Equipment 

Personnel are usually familiar with “fire drills” through participation in 

regular emergency evacuation testing of buildings. Effective disaster planning borrows that concept and conducts the same types of rehearsals for 

other high-risk emergency situations. Exercising realistic scenarios not only 

provides practical training but also ‘”tests” the emergency plans for deficiencies or vulnerabilities. Similarly, emergency equipment should be tested 

and maintained in working order. Finally, the Disaster Plan should be made 

readily available to all staff members. Some facilities have the plan available 

on internal Web sites. 

Conclusion 

Animal facility management should recognize that emergencies and 

unexpected problems are inevitable. Adopting the mindset that emergencies are a fact of life and will occur is the first step towards their prevention. 

Preparedness is critical for emergency avoidance and can reduce, if not 

eliminate, negative affects. A good Disaster Plan will ensure a quick and 

effective response and faster recovery. However, the process of emergency 

management planning is not totally intuitive and a specific effort needs 

to be made to examine the issues and devise plans. Furthermore, because 

there are no “formulas” and very few formal requirements for back-up 

or emergency systems, one facility’s plan will not be 100% effective at 

another facility. The overall process should be dynamic and should be 

reviewed on a regular basis by the facility. The IACUC may also choose 

to include it periodically as a part of their semiannual program reviews. The 

modification or upgrading of functional systems is an ideal time to upgrade 

the emergency handling potential of the system. Unfortunately, emergency/ 

hazard identification is clearest in retrospect, but the special efforts of prospective disaster planning pay the greatest dividends. 
B.6. Emergency Preparedness 79 

B.6. Table A. Examples of Categories of Emergencies 

Natural Emergencies 

Primary Emergency Secondary Effects Risk of Occurrence Impact 

Earthquake 

Flood 

Coastal flood 

Hurricanes 

Landslides 

Severe storms 

(thunderstorms) 

Tornadoes 

Tsunamis 

Wildland fires 

Winter storms 

(snow and ice) 

Drought 

Lightning 

Technical Emergencies 

Primary Emergency Secondary Effects Risk of Occurrence Impact 

Hazardous chemicals spill 

Radioisotope spill 

Biohazard spill 

Computer system 

HVAC 

Steam heat 

Water supply 

Reverse osmosis or 

treated drinking water 

Waste water removal 

Solid waste removal 

Security system 

Transportation 

Communication 

Fire safety 

Electricity 

Continued on page 80 
80 B. Oversight of the Animal Care and Use Program 

B.6. Table A. Examples of Categories of Emergencies (continued) 

Civil Emergencies 

Primary Emergency Secondary Effects Risk of Occurrence Impact 

Terrorist threat/action 

Strike of personnel 

Demonstrations 

Intrusion 

Computer/network attack 

B.6. Table B. Core Functions of an Animal Facility 

Mechanical Personnel 

• Ventilation 

• Cooling 

• Heating 

• Cleaning water 

• Drinking water for animals 

• Power 

• Sewage 

• Solid waste removal 

• Carcass disposal 

• Freezing 

• Cage sanitation 

• Communication system 

• Transportation 

• Shelter 

• 

• 

• 

• 

• 

• 

• 

• 

• 

Safety 

Communications 

– Staff


– Authorities


– Public


Medical care


Veterinary care


Husbandry


– Feeding


– Watering


– Cleaning


– Capturing loose animals


Medical waste handling


Carcass disposal


Security


Supplies


– Food


– Bedding


– Uniforms


– Personal safety equipment


– Cleaning

B.6. Emergency Preparedness 81 

Suggested Reading 

Anderson, S. 1998. Hazard Analysis: Preparing for Natural Disasters, Lab Animal 

27(1):24-29. 

Federal Emergency Management Agency (FEMA) Web site: www.fema.gov. 

“Animal in Disaster” a two module training program by FEMA. 

Vogelweid, C. M. Developing emergency management plans for university laboratory animal programs and facilities. Contemporary Topics on Laboratory Animal 

Science 37(5):52-56. 

Resources for Crisis Management in Zoos and other Animal Care Facilities. 1999. 

Published by the American Association of Zoo Keepers. Editors: Chan S. D., W. K. 

Baker, and D.L. Guerrero. Topeka, Kansas. 

Heath, S. E. 1999. Animal Management in Disaster. Mosby Year Book. St Louis, MO. 
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C. Review of Proposals 

83

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C.1. Fundamental Issues 

The IACUC is responsible for overseeing and evaluating all aspects of 

animal care and use, and is charged with reviewing proposals* that involve 

animals to ensure that the criteria established in the PHS Policy and the 

Animal Welfare Regulations (AWRs) are implemented. In its review of proposals, the Committee’s primary goal should be to facilitate compliance 

with applicable laws, regulations and policies consistent with the performance of appropriate and productive scientific endeavors. 

Protocol Review Criteria 

Table A lists each review criterion of the PHS Policy and AWRs along with 

the applicable US Government Principles. Since the PHS Policy further 

requires that the provisions of the Guide apply, there are many other 

aspects of research that an IACUC should review, such as food and water 

deprivation, use of noxious stimuli, and physical restraint. The Guide 

provides useful guidance on these and other practices. Section C.2. Protocol Review Criteria addresses many of the subjects described below in 

greater detail. 

If the IACUC does not have the scientific and technical expertise to evaluate all aspects of a proposal it may bring in outside expert consultants to 

provide information. Such consultants may not vote. In all cases, the onus 

should be on the investigator to justify and explain his or her proposed 

experiments to the satisfaction of the IACUC. 

*This Guidebook generally uses the term “proposal” to describe the proposed use of animals. In some cases the term “protocol” is used for ease of readability. For the purposes of 

this Guidebook “proposal” is interchangeable with the commonly accepted use of the 

term “protocol.” 

85 
86 C. Review of Proposals 

C.1. Table A.	 Regulatory Criteria Applicable to Protocol Review as 

Defined in PHS Policy and USDA Regulations 

U.S. Government Principles PHS Policy on USDA AWR 9 CFR Part 2, 

Note: Citations at the end of Humane Care and Use Subpart C 

each Principle refer to other of Laboratory Animals 

Sections of this Guidebook. 

Principle I: The transportation, 

care and use of animals should 

be in accordance with the AWA 

(7 U.S.C.2131 et. seq.) and 

other applicable federal laws, 

guidelines, and policies*. 

*For guidance throughout 

these Principles, the reader 

is referred to the Guide. 

Principle II: Procedures involving 

animals should be designed and 

performed with due consideration of their scientific relevance 

to human or animal health, the 

advancement of knowledge, or 

the good of society. 

Principle III: The animals 

selected for a procedure 

should be of an appropriate 

species and quality and the 

minimum number required to 

obtain valid results. Methods 

such as mathematical models, 

computer simulation, and 

in vitro biological systems 

should be considered. 

(See C.2.a. Alternatives) 

C.1.: ...the IACUC 

shall...determine that the 

proposed research projects 

are in accordance with this 

Policy...the IACUC shall confirm that the research project 

will be conducted in accordance with the AWA insofar as 

it applies to the research project, 

and that the research project is 

consistent with the Guide unless 

acceptable justification for a 

departure is presented. 

D.1.: Applications and 

proposals...that involve the 

care and use of animals shall 

contain the following: a.) 

Identification of the species 

and the approximate number 

of animals to be used; b.) 

rationale for involving animals, 

and for the appropriateness 

of the species and numbers 

of animals to be used... 

§2.31(d): ...The IACUC shall 

determine that the proposed 

activities are in accordance 

with this subchapter unless 

acceptable justification for 

a departure is presented 

in writing... 

§2.31(d)(1)(iii): The PI has 

provided written Assurance 

that the activities do not 

unnecessarily duplicate 

previous experiments. 

§2.31(e): A proposal...must 

contain the following: (1) 

Identification of the species 

and approximate number of 

animals to be used; (2) A 

rationale for involving animals, 

and for the appropriateness 

of the species and numbers 

of animals to be used... 
C.1. Fundamental Issues 87 

C.1. Table A.	 Regulatory Criteria Applicable to Protocol Review as 

Defined in PHS Policy and USDA Regulations (continued) 

U.S. Government PHS Policy on USDA AWR 9 CFR Part 2, 

Principles Humane Care and Use Subpart C 

of Laboratory Animals 

Principle IV: Proper use of 

animals, including the avoidance or minimization of 

discomfort, distress, and 

pain when consistent with 

sound scientific practices, 

is imperative. Unless the 

contrary is established, 

investigators should consider 

that procedures that cause 

pain or distress in human 

beings may cause pain or 

distress in other animals. 

(See C.2.a. Alternatives, and 

C.2.d. Minimization of Pain 

and Distress) 

Principle V: Procedures 

with animals that may 

cause more than 

momentary or slight 

pain or distress should 

be performed with 

appropriate sedation, 

analgesia, or anesthesia. 

Surgical or other painful 

procedures should 

not be performed 

on unanesthetized 

animals paralyzed 

by chemical agents. 

(See C.2.c. Humane 

Endpoints, and C.2.d. 

Minimization of Pain and 

Distress, and C.2.f. Veterinary 

Review and Consultation) 

IV.C.1.a.: Procedures with 

animals will avoid or minimize 

discomfort, distress, and pain 

to the animals, consistent with 

sound research design. 

IV.C.1.b.: Procedures that 

may cause more than 

momentary or slight pain 

or distress to the animals 

will be performed with 

appropriate sedation, 

analgesia, or anesthesia, 

unless the procedure 

is justified for scientific 

reasons in writing by the 

investigator (and approved 

by the IACUC). 

§2.31(d)(1)(i): Procedures 

involving animals will avoid 

or minimize discomfort, distress, and pain to the animals; 

(ii) the principal investigator 

has considered alternatives 

to procedures that may cause 

more than momentary or slight 

pain or distress to the animals, 

and has provided a written 

narrative description of the 

methods and sources, e.g., 

the Animal Welfare Information 

Center, used to determine that 

alternatives were not available. 

(See also §2.31(e)(4)). 

§2.31(d)(1)(iv): Procedures 

that may cause more than 

momentary or slight pain 

or distress to the animals 

will: (A) Be performed with 

appropriate sedatives, 

analgesics or anesthetics, 

unless withholding such 

agents is justified for 

scientific reasons, in 

writing, by the principal 

investigator and will continue for only the necessary 

period of time; (B) Involve, 

in their planning, consultation with the attending 

veterinarian or his or her 

designee; (C) Not include 

the use of paralytics 

without anesthesia. 

Continued on page 88 
88 C. Review of Proposals 

C.1. Table A.	 Regulatory Criteria Applicable to Protocol Review as 

Defined in PHS Policy and USDA Regulations (continued) 

U.S. Government PHS Policy on USDA AWR 9 CFR Part 2, 

Principles Humane Care and Use Subpart C 

of Laboratory Animals 

Principle VI: Animals that would 

otherwise suffer severe or 

chronic pain or distress that 

cannot be relieved should be 

painlessly killed at the end of 

the procedure or, if appropriate, 

during the procedure. 

(See C.2.b. Euthanasia) 

Principle VII: The living 

conditions of animals should be 

appropriate for their species and 

contribute to their health and 

comfort. Normally, the housing, 

feeding, and care of all animals 

used for biomedical purposes 

must be directed by a veterinarian or other scientist trained and 

experienced in the proper care, 

handling, and use of the species 

being maintained or studied. In 

any case, veterinary care shall 

be provided as indicated. 

(See B.2.b. Animal Environment, 

B.2.c. Husbandry, and B.3. 

Role of the Veterinarian) 

Principle VIII: Investigators and 

other personnel shall be appropriately qualified and experienced 

for conducting procedures on 

living animals. Adequate arrangements shall be made for their 

in-service training, including the 

proper and humane care and 

use of laboratory animals. 

(See C.2.e. Personnel 

Qualifications) 

IV.C.1.c.: Animals that would 

otherwise experience severe 

or chronic pain or distress 

that cannot be relieved will 

be painlessly killed at the end 

of the procedure or, if appropriate, during the procedure. 

IV.C.1.g.: Methods of euthanasia will be consistent with 

the recommendations of the 

AVMA Panel on Euthanasia, 

unless a deviation is justified 

for scientific reasons in writing by the investigator [and 

approved by the IACUC]. 

IV.C.1.d.: The living conditions 

of animals will be appropriate 

for their species and contribute 

to their health and comfort. 

The housing, feeding, and 

non-medical care of the animals 

will be directed by a veterinarian 

or other scientist trained and 

experienced in the proper care, 

handling, and use of the species 

being maintained or studied. 

IV.C.1.e.: Medical care for 

animals will be available and 

provided as necessary by a 

qualified veterinarian. 

IV.C.1.f.: Personnel conducting 

procedures on the species being 

maintained or studied will be 

appropriately qualified and 

trained in those procedures. 

§2.31(d)(1)(v): Animals that would 

otherwise experience severe 

or chronic pain or distress that 

cannot be relieved will be painlessly euthanized at the end 

of the procedure or, if appropriate, during the procedure. 

§2.31(d)(1)(xi): Methods of 

euthanasia used must be in 

accordance with the definition 

of the term set forth in 9 CFR 

part 1, §1.1 of this subchapter, 

unless a deviation is justified 

for scientific reasons, in writing, by the investigator. 

§2.31(d)(1)(vi): The animals’ living 

conditions will be appropriate 

for their species in accordance 

with part 3 of this subchapter, 

and contribute to their health 

and comfort. The housing, feeding, and nonmedical care of the 

animals will be directed by the 

attending veterinarian or other 

scientist trained and experienced 

in the proper care, handling, 

and use of the species being 

maintained or studied. 

§2.31(d)(1)(vii): Medical care for 

animals will be available and 

provided as necessary by a 

qualified veterinarian. 

§2.31(d)(1)(viii): Personnel 

conducting procedures on 

the species being maintained 

or studied will be appropriately 

qualified and trained in those 

procedures. 
C.1. Fundamental Issues 89 

C.1. Table A.	 Regulatory Criteria Applicable to Protocol Review as 

Defined in PHS Policy and USDA Regulations (continued) 

U.S. Government PHS Policy on USDA AWR 9 CFR Part 2, 

Principles Humane Care and Subpart C 

Use of Laboratory Animals 

Principle IX: Where exceptions 

are required in relation to the 

provisions of these Principles, 

the decisions should not rest 

with the investigators directly 

concerned but should be made, 

with due regard to Principle II, 

by an appropriate review group 

such as an institutional animal 

care and use committee. Such 

exceptions should not be made 

solely for the purposes of 

teaching or demonstration. 

See C.1. above. 

D.1.: Applications and 

proposals... that involve the 

care and use of animals shall 

contain the following: ...c) a 

complete description of the 

proposed use of the animals... 

D.1.: Applications and 

proposals...that involve the 

care and use of animals shall 

contain the following: ...d) a 

description of procedures 

designed to assure that discomfort and injury to animals 

will be limited to that which is 

unavoidable in the conduct 

of scientifically valuable 

research, and that analgesic, 

anesthetic, and tranquilizing 

drugs will be used where 

indicated and appropriate to 

minimize discomfort and pain 

to animals. 

See §2.31(d) above. 

§2.31(e): A proposal...must 

contain the following: ... 

(3) A complete description 

of the proposed use of 

the animals... 

§2.31(e): A proposal...must 

contain the following: ... 

(4) A description of procedures designed to assure that 

discomfort and pain to animals 

will be limited to that which is 

unavoidable for the conduct of 

scientifically valuable research, 

including provision for the use 

of analgesic, anesthetic, and 

tranquilizing drugs where 

indicated and appropriate 

to minimize discomfort and 

pain to animals. 

Continued on page 90 
90 C. Review of Proposals 

C.1. Table A.	 Regulatory Criteria Applicable to Protocol Review as 

Defined in PHS Policy and USDA Regulations (continued) 

U.S. Government PHS Policy on USDA AWR 9 CFR Part 2, 

Principles Humane Care and Subpart C 

Use of Laboratory Animals 

§2.31(d)(1) (ix): Activities that 

involve surgery include appropriate provision for pre-operative 

and post-operative care of the 

animals in accordance with 

established veterinary medical 

and nursing practices. All 

survival surgery will be performed using aseptic procedures, including surgical gloves, 

masks, sterile instruments, 

and aseptic techniques. Major 

operative procedures on nonrodents will be conducted only 

in facilities intended for that 

purpose which shall be operated 

and maintained under aseptic 

conditions. Non-major operative 

procedures and all surgery on 

rodents do not require a dedicated facility, but must be 

performed using aseptic procedures. Operative procedures 

conducted at field sites need 

not be performed in dedicated 

facilities, but must be performed 

using aseptic procedures; 

§2.31(d) (1) (x): No animal will 

be used in more than one major 

operative procedure from which 

it is allowed to recover, unless: 

(A) justified for scientific reasons 

by the principal investigator, in 

writing; (B) Required as routine 

veterinary procedure or to protect the health or well-being of 

the animal as determined by the 

attending veterinarian, or (C) In 

other special circumstances as 

determined by the Administrator 

on an individual basis. 
C.1. Fundamental Issues 91 

Proposal Review Procedures 

The procedural review requirements of the PHS Policy or the AWRs take 

precedence even though they may differ from some commonly used parliamentary procedures. Institutions may develop their own meeting procedures as long as the procedures do not contradict or are not inconsistent 

with the requirements of the PHS Policy or the AWRs. 

If a proposal may cause more than momentary or slight pain or distress to 

animals, the AWRs specifically require investigators to consult with the AV 

or his or her designee during protocol development. Some committees find 

it helpful to assign a member a given proposal for in-depth review and 

liaison with the investigator prior to committee review. Still other committees assign this task to professional IACUC staff. The investigator may 

choose to consult with these individuals and request a preliminary review 

before formally submitting a proposal. 

The PHS Policy and AWRs recognize two methods of review: full committee review and designated member review. The following pertains to 

review of initial protocols as well as to review of proposed significant changes 

in previously approved protocols. 

• Full committee review 

Full committee review of proposals requires a convened 

meeting of a quorum of the IACUC members. The PHS Policy 

and AWRs are explicit that proposals reviewed by the full 

committee must receive the approval vote of a majority 

(>50%) of the quorum present in order receive approval (see 

A.2. Quorum requirements). 

Some committees designate a specific member or members 

to serve as primary or primary and secondary reviewers. 

These individuals, usually chosen for their expertise or 

familiarity with a given topic, are responsible for an in-depth 

review of a proposal and sometimes take responsibility for 

describing the proposal to the full committee and answering 

questions about the proposal during review by the Committee. Primary and secondary reviewers can also take the 

initiative to contact the investigator prior to the meeting for 

clarifications, additional information, or in anticipation 

of questions the IACUC may raise. The use of primary 
92 C. Review of Proposals 

reviewers facilitates full committee review by distributing 

the workload among IACUC members so that each member 

has responsibility for in-depth review of only a portion of the 

proposals the IACUC will review. It differs from designated 

member review (see below), which invests authority to 

approve a proposal in one or more members. 

Review of proposals by the full committee method invokes 

a deliberative process, and the PHS Policy and AWRs 

require that minutes of IACUC meetings reflect committee 

deliberations. Minutes should include records of attendance, 

a summary of the issues discussed and the resolution of 

issues, and the results of IACUC votes on proposals. 

Participation by investigators in meetings in which their 

proposal is being reviewed is not addressed by either the 

PHS Policy or the AWRs. The participation of the investigator can facilitate the review in a number of ways. Obviously 

questions can be addressed as they are raised rather than 

after the meeting, allowing the review process to proceed 

rather than be interrupted for this exchange of information. 

Another benefit is the opportunity for the investigator to give 

a broad overview of how the proposal under review fits 

into the larger research picture, thus providing additional 

information regarding the justification and scientific merit. 

Invariably, both the investigator and the IACUC benefit from 

such an exchange. The greatest deterrents to participation 

by investigators in the IACUC meeting are that it may make 

the meeting last longer, and problems arise if this is an 

adversarial rather than collegial exchange of information. 

In any event, the investigator should leave before the final 

committee deliberations and if he or she is a committee 

member may not contribute to a quorum or vote. 

• Designated member review 

To utilize designated member review, each IACUC member 

must be provided with at least a list of the proposed research 

protocols or proposed significant changes to previously 

approved protocols prior to the review. Most committees 

provide members with an abstract of proposals; in all cases, 

written descriptions of the research proposals must be made 

available to IACUC members upon request. All members must 
C.1. Fundamental Issues 93 

have the opportunity to request full committee review of any 

proposal. If no member requests full committee review, the 

Chair designates one or more qualified members to review 

the proposal (or proposed amendment). These designated 

members have authority to approve, require modifications in 

(to secure approval), or request full committee review. 

IACUCs with a large volume of proposals to be reviewed 

find the designated member review option may allow for 

efficient management of the IACUC workload as well as timely 

turnaround of requests from investigators for protocol 

review. Some committees prefer to reserve the designated 

member review option for certain classes of protocols 

or amendments; conversely, some IACUCs have devised 

categories of research activities that must be reviewed by 

the full committee, e.g., nonhuman primate studies, survival 

surgeries, etc. If the designated member review method is 

to be used by PHS-supported institutions then the IACUC’s 

specific procedures for using the method should be described 

in its PHS Assurance. 

Categories of IACUC Actions 

As a result of their review of a protocol, an IACUC may take one of several 

different actions depending upon the findings of the committee: approval, 

modifications required to secure approval, or withhold approval. An IACUC 

may also defer or table review if necessary. 

The PHS Policy and AWRs require the IACUC to notify investigators and the 

institution in writing of its decision to approve or withhold approval, or of 

modifications required to secure approval. If approval is withheld the IACUC 

must provide the reasons for its decision and give the investigator an 

opportunity to respond. 

• Approval 

When the IACUC has determined that all review criteria, 

based on the PHS Policy and AWRs, have been adequately 

addressed by the investigator, the IACUC may approve the 

proposal, thus providing the investigator permission to perform the experiments or procedures as described. 

An IACUC-approved proposal may be subject to further 

appropriate review and approval by institutional officials due 
94 C. Review of Proposals 

to financial, policy, facility, or other institutional or administrative considerations. However, those officials may not 

approve an activity if it has not been approved by the IACUC. 

• Modifications required to secure approval 

An IACUC may require modifications to the proposal before 

granting approval. If the IACUC determines that a proposal 

is approvable contingent upon receipt of a very specific 

modification (e.g., receipt of assurance that the procedure 

will be conducted in a fume hood), or clarification of a specific point, the IACUC may handle these modifications or 

clarifications as administrative details that an individual, such 

as the Chair, could verify. 

If a study is unusually complex or involves untried or 

controversial procedures the IACUC may wish to impose 

restrictions, (e.g., approval for the use of a limited number of 

animals as a pilot study with a written report of interim 

results, or close monitoring by veterinary or other qualified 

personnel.) If such modifications represent significant 

departures the IACUC can ask the investigator to revise the 

protocol to reflect the modifications imposed by the IACUC. 

If the proposal is missing substantive information necessary 

for the IACUC to make a judgment, or the IACUC requires 

extensive or multiple modifications, then the IACUC can 

require that the protocol be revised and resubmitted. If the 

IACUC wishes to shift to the designated reviewer mode for 

the approval of the modified protocol, that shift should 

be explicitly noted in the minutes and the requirements for 

designated review must be met. 

IACUCs sometimes use terms such as “conditional approval,” 

“provisional approval” or “approved pending clarification.” 

Anything less than full IACUC approval via one of the 

accepted methods described above is not adequate for 

initiation of animal activities or for submission of an IACUC 

approval date to PHS in conjunction with a grant application. Therefore, OLAW and USDA recommend that IACUCs 

either avoid using these terms, or describe them (e.g., in 

IACUC minutes, Assurance documents, etc.) in sufficient 

detail to be fully understood. 
C.1. Fundamental Issues 95 

• Withhold approval 

When the IACUC determines that a proposal has not 

adequately addressed all of the requirements of the PHS 

Policy and AWRs as applicable, the committee may withhold approval. A designated reviewer may not withhold 

approval; this action may only be taken if the review is 

conducted using the full committee method of review. 

As indicated above, a higher institutional authority may not 

administratively overrule an IACUC decision to withhold 

approval of a proposal. 

• Defer or table review 

If the proposal requires clarification in order for the IACUC 

to make a judgment, committee members with certain 

expertise are not present, the IACUC wishes to seek external consultation, or any of a number of other reasons 

prevent the IACUC from conducting its review, then the 

IACUC may wish to defer or table review. Good communication between the IACUC and the investigator can ensure 

that this action is needed infrequently. However, should it 

be necessary, the investigator should be informed so that 

he or she can respond or plan accordingly. 

Review of Changes to Approved Protocols 

Significant changes to an IACUC-approved protocol must be reviewed and 

approved by the IACUC before they occur (PHS Policy IV.C.1., and AWR 

§2.31[d][1]). It is prudent for an IACUC to develop a policy on the kinds of 

changes that are considered significant in order to avoid ambiguity. OLAW 

has identified the following kinds of significant changes that may serve as 

examples to guide the IACUC in its determinations: 

• change in objectives of a study; 

• proposals to switch from nonsurvival to survival surgery; 

•	 change in degree of invasiveness of a procedure or discomfort to an 

animal; 

• change in species or in the approximate number of animals used; 

• change in personnel involved in animal procedures; 

• change in anesthetic agent(s) or in the use or withholding of analgesics; 
96 C. Review of Proposals 

• change in methods of euthanasia; or 

•	 change in duration, frequency or number of procedures performed on 

an animal. 

Review of significant changes may be conducted using either the full committee review or the designated member review method described above. 

Frequency of Review of Approved Protocols 

The PHS Policy requires that a complete IACUC review of PHS supported 

protocols be conducted at least once every three years. This triennial 

review is interpreted by OLAW as a requirement for de novo review, meaning that the criteria and procedures for review specified in IV.C. of the PHS 

Policy must be applied not less than once every three years. The three-year 

period begins on the actual date of IACUC approval; IACUCs may not 

administratively extend approval beyond the three years. The triennial 

review may be conducted using either the full committee review or the designated member review method described above. 

AWRs require an annual review, which may be a monitoring mechanism whereby the IACUC requires the investigator to annually report on the 

status of the protocol, verify that completed activities were conducted in 

accordance with the approved protocol, describe any proposed departures 

from the approved protocols, and solicit information about activities projected for the upcoming year. (Proposed significant changes would require 

IACUC review prior to initiation.) This kind of a monitoring system will 

satisfy the AWR requirement for annual review, but would not be sufficient 

for the complete IACUC review required on a triennial basis. 

References 

Garnett, N.L. and W.R. DeHaven. Commentary: Protocol Review – Playing By the 

Rules. Lab Animal 27(8):18. 1998. 

Potkay, S., et al. Frequently Asked Questions about the Public Health Service Policy 

on Humane Care and Use of Laboratory Animals. Lab Animal 24(9):24-26. 1995. 

OPRR Staff. The Public Health Service Responds to Commonly Asked Questions. 

ILAR News 33(4):68-70, Fall, 1991. 

OPRR Staff. Frequently Asked Questions about the Public Health Service Policy on 

Humane Care and Use of Laboratory Animals. ILAR News 35(3-4):47-49, Summer/ 

Fall, 1993. 

Oki, G.S.F., et al. Model for Performing Institutional Animal Care and Use Committee Continuing Review of Animal Research. Contemporary Topics 35(5):53-56, September 1996. 
C.2. Protocol Review Criteria 

C.2.a. Alternatives – Replacement, Reduction and Refinement 

There is significant interest in the application of alternatives to animals used 

in research, education and testing. The PHS Policy and the AWRs require 

research institutions to ensure that investigators have appropriately considered alternatives to procedures that can cause more than slight or 

momentary pain or distress in animals, consistent with sound research 

design. Through U.S. Government Principle III (Appendix F), the PHS Policy 

further requires that the minimum number of animals be used and that 

non-animal methods be considered. 

The “3 Rs” 

Alternatives are framed within the context of the “3 Rs” articulated originally 

by Russell and Burch in 1959; they include: 

1. Replacement, or utilizing non-animal models; 

2. Reduction of numbers of animals used; and 

3. Refinement, or elimination or reduction of unnecessary pain and 

distress in animals. 

Replacement alternatives utilize: 

• living systems, 

• non-living systems, or 

• computer simulations. 

Living systems include in vitro methods that utilize organ, tissue or cell 

culture techniques. Invertebrate animals, such as the fruit fly, have long 

been used in research and represent another type of living alternative to 

vertebrate animals. Finally, microorganisms and plants represent living 

alternatives for some types of research and testing. If no invertebrate model 

is appropriate, use of species lower on the phylogenetic scale may be considered a replacement alternative. 

97 
98 C. Review of Proposals 

Nonliving systems include physical or mechanical systems and chemical 

techniques. Mechanical models may be used in the training of specific techniques (cardiopulmonary resuscitation, for example) and have replaced 

living animals in some cases. Chemical techniques are the most widely used 

nonliving systems and include such useful systems as the enzyme linked 

immunosorbent assay (ELISA). Techniques that identify the presence of 

chemical reactions and enzymes, or simply analyze chemical structure, can 

all be useful in the prediction of toxicity without the use of animals. 

Computer simulations may replace some animal use and can be particularly useful when a question is well defined and there is existing data. 

Although opportunities for replacement are numerous in product safety 

testing and education, they appear more limited in research. If it is 

demonstrated that there is no in vitro alternative to the use of animals, it 

is important for the IACUC members to focus on the other alternative 

approaches, reduction and refinement. 

Reduction of numbers of animals may be accomplished by a variety of 

methods described in Table A: 

C.2.a. Table A. Methods for Reduction of Numbers of Animals Used 

Method Examples 

Rational selection of group size • Pilot studies to estimate variability 

and evaluate procedures and effects 

• Power analysis 

Careful experimental design • Appropriate choice of control groups 

• Standardizing procedures to minimize variability 

Maximizing use of animals • Performing several terminal procedures 

per animal 

• Animals euthanized by one investigator 

used for tissue needed by another 

Correct choice of model • Use of healthy, genetically similar animals 

decreases variability 

Minimizing loss of animals • Good post-operative care 

• Avoid unintended breeding 

• Plan ahead so the appropriate number 

of animals needed for studies are ordered 

or bred 

Statistical analysis • Appropriate use of statistical software 

can generate maximum information 

from minimum number of animals 
C.2. Protocol Review Criteria 99 

Refinement of technique to reduce or eliminate unnecessary pain and 

distress in study animals is the most commonly practiced of the 3 Rs, 

although it is not always recognized as one of the applications. 

Investigators are required to consider alternatives to painful procedures, 

and to avoid or minimize discomfort, distress and pain, consistent with sound 

scientific practice and the goals of the research. This requires an understanding of the potential of pain or distress in the animals (see Section 

C.2.d.). 

When there is no consensus among IACUC members as to whether a 

certain procedure actually causes pain or distress in the affected animals, 

U.S. Government Principle IV should be applied. This Principle states, 

“Unless the contrary is established, investigators should consider that 

procedures that cause pain or distress in human beings may cause pain 

or distress in other animals.” 

To assist in this deliberation, the IACUC may need to utilize one or more of 

the following: 

• pilot studies, 

• evaluations of clinical signs, 

• clinical pathology, 

• gross and histological necropsy studies, 

• review of comparable literature, and 

• consultation with experts. 

If there remains any doubt about the presence of pain or distress, the IACUC 

should err on the side of protecting the animals against the potential of 

unnecessary pain or distress. 

Some refinement opportunities include: 

• pain-relieving drugs, 

• non-pharmacologic techniques, 

• new diagnostic and therapeutic techniques, 

• environmental enrichment programs, and 

• establishment of more humane endpoints. 
100 C. Review of Proposals 

Pain-relieving drugs: While it is preferable to design a protocol that 

prevents pain and distress, when this is not possible the AWRs require that 

the AV (or designee) be consulted to develop an appropriate plan for 

the use of anesthetics, analgesics, or other measures, such as antiinflammatory agents, antibiotics, or sedatives. 

New diagnostic and therapeutic techniques: In addition to the use of pain 

relieving drugs, new diagnostic and therapeutic techniques may have the 

capability to dramatically reduce the invasiveness of data collection and 

thereby refine animal research. These include: 

•	 use of sophisticated imaging equipment to replace invasive procedures, and 

•	 blood and tissue sampling techniques that allow for easier collection 

and the processing of smaller sample sizes. 

Environment: The IACUC should consider that environmental factors, such 

as noises, odors, infrequent or inexperienced handling, or boredom from 

lack of environmental stimulation can cause unnecessary distress, and that 

US Government Principle IV should be applied to this area as well. Aside 

from the AWR requirement to provide environment enhancement for nonhuman primates, many institutions have implemented environmental modifications for other species with a view to reducing unnecessary distress. 

Humane endpoints: The establishment of the earliest possible humane 

endpoint consistent with the research design may provide an additional 

opportunity to significantly reduce pain and distress, thereby refining the 

experiment. For any study that defines death of the experimental animal as 

the endpoint, the IACUC should ask if there is an earlier point in the study 

when the necessary data have been collected and the animal could be 

euthanized without proceeding through more severe illness and death. Or, 

alternatively, if death is a necessary endpoint, the IACUC could ask for careful 

ongoing assessment of the animal, so that, when it is determined that death 

is inevitable, the animal can be euthanized. The Canadian Council on 

Animal Care Guidelines on Choosing an Appropriate Endpoint in Experiments Using Animals for Research, Teaching and Testing (1998) is an excellent resource for IACUCs. (See also Section C.2.c. Humane Endpoints.) 
C.2. Protocol Review Criteria 101 

USDA Requirements for Consideration of Alternatives 

USDA AWRs require that investigators consider alternatives to procedures that may cause more than momentary or slight pain or distress and 

provide a written narrative of the methods used and sources consulted to 

determine availability of alternatives. Animal Care Policy 12 provides 

guidance on the requirements for the written narrative, which should 

include adequate information for the IACUC to assess that a reasonable 

and good faith effort was made to determine the availability of alternatives 

or alternative methods. Resources in the area of alternatives include the 

USDA Animal Welfare Information Center (AWIC); ALTWEB, a Web site 

maintained under the auspices of the Johns Hopkins University Center for 

Alternatives to Animal Testing; and the University of California Center for 

Animal Alternatives (see Appendix A). 

C.2.b. Euthanasia 

“Euthanasia means the humane destruction of an animal accomplished by 

a method that produces rapid unconsciousness and subsequent death 

without evidence of pain or distress, or a method that utilizes anesthesia 

produced by an agent that causes painless loss of consciousness and 

subsequent death” (AWR). The choice of a method depends on species, 

age, availability of restraint, skill of the individuals performing euthanasia 

and other considerations. In a research setting, the method of euthanasia 

must be consistent with the research goals. 

The PHS Policy and the AWRs require that an IACUC review and approve 

methods of euthanasia. The PHS Policy specifically states that methods of 

euthanasia must be consistent with the recommendations of the American 

Veterinary Medical Association (AVMA) Panel on Euthanasia, unless scientific justifications for alternative methods are presented in writing by the 

investigator and approved by the IACUC. The most recent Panel convened 

in 2000, and published its Report in March 2001. 

The criteria used as the basis for the Panel’s recommendations include: 

• minimum pain, distress, anxiety or apprehension; 

• minimum delay until unconsciousness; 

• reliability and irreversibility; 

• safety of personnel; emotional effect on personnel; 
102 C. Review of Proposals 

•	 compatibility with requirement and purpose, including subsequent use 

of tissue; 

• compatibility with species, age and health status; and 

• drug availability and human abuse potential. 

Recommended Methods 

The 2000 Report of the AVMA Panel on Euthanasia categorizes methods 

as acceptable, conditionally acceptable, or unacceptable under specific circumstances. 

Acceptable 

a. Barbiturates (most species) 

b. Carbon dioxide (CO2)-bottled gas only (most species) 

c. Inhalant anesthetics (most species) 

d. Microwave irradiation (mice and rats) 

e. Tricaine methane sulfate (TMS, MS222) (fish, amphibians) 

f. Benzocaine hydrochloride (fish, amphibians) 

g. Captive penetrating bolt (horse, ruminant, swine) 

h. Ether and carbon monoxide are acceptable for many species, but 

relatively dangerous to personnel. 

Conditionally Acceptable (Requires IACUC Approval of Scientific Justification) 

a. Cervical dislocation (birds, small rodents and rabbits) 

b. Decapitation (birds, rodents, some other species) 

c. Pithing (some ectotherms) 

d. Various pharmacological and physical methods 

Unacceptable 

a. Chloral hydrate, chloroform and cyanide 

b. Decompression 

c. Neuromuscular blockers 

d. Various pharmacological and physical methods 

e. Dry ice-generated Co2 
C.2. Protocol Review Criteria 103 

Methods described as conditionally acceptable are considered acceptable 

when used in deeply anesthetized animals. Some euthanasia methods (e.g., 

KCl or formalin by intracardiac injection, or exsanguination) are acceptable 

only under deep general anesthesia. 

For more information on methods of euthanasia see Appendix D. 

C.2.c. Humane Endpoints 

Animals used in research and testing may experience pain from induced 

diseases, procedures, and toxicity. The PHS Policy and AWRs state that 

procedures that cause more than momentary or slight pain or distress should 

be performed with appropriate sedation, analgesia, or anesthesia. However, research and testing studies sometimes involve pain that cannot be 

relieved with such agents because they would interfere with the scientific 

objectives of the study. Accordingly, federal regulations require that IACUCs 

determine that discomfort to animals will be limited to that which is 

unavoidable for the conduct of scientifically valuable research, and that 

unrelieved pain and distress will only continue for the duration necessary 

to accomplish the scientific objectives. 

The PHS Policy and AWRs further state that animals that would otherwise 

suffer severe or chronic pain and distress that cannot be relieved should 

be painlessly killed at the end of the procedure, or if appropriate, during 

the procedure. 

Developing Humane Endpoints 

Criteria used to end experimental studies earlier in order to avoid or terminate unrelieved pain and/or distress are referred to as humane endpoints. 

An important feature of humane endpoints is that they should ensure that 

study objectives will still be met even though the study is ended at an earlier 

point. Ideally, humane endpoints are sought that can be used to end studies before the onset of pain and distress. 

It is important to understand that stress may lead to distress when major 

shifts in biologic function, to which the animal cannot adapt, threaten the 

animal’s well-being. If pain and distress are anticipated, a detailed plan for 

when and how these will be alleviated should be provided in the protocol. 
104 C. Review of Proposals 

The plan should include detailed written criteria for the humane endpoints 

that will be used to determine when animals can be removed from the study, 

treated, or euthanized. There should be clear directions concerning who 

can make the decision to euthanize or treat animals, including procedures 

to follow if a situation arises on weekends, holidays, or in the absence of 

the responsible study director. 

Even if pain or distress are not anticipated, every protocol should contain a 

contingency plan for dealing with unexpected situations that may arise. 

The development and use of humane endpoints can reduce the severity 

and duration of unrelieved pain and distress. Clinical score sheets can be 

developed and used to establish humane endpoints for experimental 

studies. Score sheets are used to record and identify clinical signs and conditions associated with a particular experimental model. Single or multiple 

clinical signs that are predictive of the current experimental endpoint can 

then be used to allow for earlier and more humane endpoints. 

Establishing and implementing humane endpoints is best achieved by a 

collaborative effort on the part of investigators, veterinarians, and animal 

care staff. 

Moribund Condition as a Humane Endpoint 

Moribund has been defined as “in the state of dying,” or “at the point of 

death.” A moribund condition may be an appropriate humane experimental 

endpoint for some studies where there is the induction of severe disease 

states and high rates of mortality. Pre-emptive euthanasia of moribund animals can prevent further pain and distress. 

Objective data-based criteria that are predictive of impending death can be 

used to implement timely euthanasia to avoid spontaneous deaths. FDA 

regulatory testing guidelines allow for humane killing of animals that are 

moribund. However, it is important to recognize that euthanasia of a moribund animal does not eliminate pain and distress that may be experienced 

during progression to a moribund condition. It should also be noted that 

while death is not a required endpoint for routine toxicity testing, animals 

are often found dead during studies. Establishing procedures to detect and 

humanely euthanize moribund or pre-moribund animals can reduce the 

number of animals that die spontaneously. In addition to reducing animal 

pain and distress, euthanasia of moribund animals allows for the collection 

of tissues and other biologic specimens that may otherwise be lost or rendered unusable when an animal is found dead. 
C.2. Protocol Review Criteria 105 

Various clinical signs are indicative of a moribund condition in laboratory 

animals. These typically include one or more of the following: 

•	 impaired ambulation which prevents animals from reaching food 

or water, 

• excessive weight loss and emaciation, 

• lack of physical or mental alertness, 

• difficult labored breathing, and 

• inability to remain upright. 

Animals should be observed frequently enough to detect signs of impending death so they can be euthanized in a timely manner. When increased 

morbidity or mortality is expected, a minimum of twice daily observation is 

recommended. Animals not likely to survive until the next scheduled observation should normally be euthanized. In situations where animals are often 

found dead, closer and more frequent observation for moribund animals 

should be considered to reduce spontaneous deaths. Euthanasia of 

animals that are moribund or experiencing severe pain and distress should 

always be done in a manner that produces the least possible amount 

of additional pain and distress. 

Other Humane Endpoints in Research 

Animals used to study tumor biology, to develop new cancer therapies, and 

to evaluate the carcinogenic potential of substances may experience pain 

and distress. Frequent and appropriate monitoring of animals during tumor 

development is necessary to allow for appropriate intervention before 

significant deterioration or death. Effective monitoring systems and endpoints should include limits on tumor size and severity of tumor-associated 

disease. Altered physiologic, biochemical, and other biomarkers may be 

potentially more objective and reproducible endpoints than clinical signs 

for such studies. 

Genetically engineered animal models are sometimes accompanied by 

unintended and unpredicted alterations that adversely affect animal wellbeing. Investigators need to establish a plan for addressing unanticipated 

adverse outcomes for genetically altered animals. There should be a plan 

for systematic characterization of phenotypes to facilitate assessment of 

their possible utility and timely decisions on disposition or retention. IACUCs 

should provide oversight of such studies to ensure that animal welfare problems are handled in an effective and prompt manner. 
106 C. Review of Proposals 

Animals with induced infections may experience significant pain and/or 

distress during progression of the disease. Early physiologic and biochemical changes during infection have been found to be useful humane 

endpoints rather than death or moribund condition. Specific decreases in 

body temperature have been found to be effective early predictors of eventual death for some infections in rodents. Vaccine potency testing typically 

involves challenging immunized animals with infectious agents. While 

such testing has commonly used lethality as the endpoint indicative of 

insufficient protection, some regulatory authorities now allow euthanasia 

of moribund animals. 

Toxicity Testing 

Animals used in toxicity testing can experience pain and distress when toxic 

effects are produced. Toxicity testing regulations allow treatment of pain 

and distress in test animals only if there is no interference with the study. As 

a result, animals are rarely treated in toxicology studies because of the 

potential confounding effects of analgesics. Consequently, management 

of pain and distress in toxicity studies is accomplished largely by euthanizing animals that are experiencing significant pain and distress. 

Current regulatory guidelines state that animals in toxicology studies 

obviously in pain or showing signs of severe and enduring distress should 

be euthanized, rather than allowing them to survive to the end of the 

scheduled study. Humane endpoints should be established and used for 

toxicology studies in order to further minimize pain and distress. 

Death as an Endpoint 

Since it provides an objective and unequivocal data point, death has 

historically been used as an endpoint in cancer, infectious disease and other 

animal studies, especially for regulatory purposes (e.g., drug safety/ 

efficacy studies). Increased public interest and regulation have led to a 

re-evaluation of this practice. Much of the concern arose from the use of 

traditional LD50 tests for chemicals and drugs to determine acute toxicity. 

However, regulatory testing requirements for acute toxicity now allow for 

animals that are moribund or exhibiting clinical signs of severe pain and 

distress to be euthanized rather than to die spontaneously. Euthanasia also 

provides tissues more appropriate for subsequent study and alleviates 

potential suffering by the animal. Hence, euthanasia is often preferable to 

death for both scientific and ethical reasons. 
C.2. Protocol Review Criteria 107 

The use of death as an endpoint is discouraged and must always be justified. Endpoints other than death must always be considered and should be 

used whenever the research objective can be attained with non-lethal endpoints. Use of death as an endpoint must be justified in writing in proposals 

and its use must be approved by the IACUC prior to beginning a study. 

C.2.c. Table A.	 Examples of Humane Endpoints for Studies with 

Potential Lethality 

Endpoint Characteristics Applications 

Tumor growth or effects Tumor exceeds 10% Subcutaneous or 

of normal body weight; intraperitoneal tumors 

necrosis, infection, ulceration, and hybridomas 

interference with ambulation 

or eating/drinking 

Prolonged inappetence/ Rapid loss of weight (>20% Metastatic disease, 

Cachexia of normal body weight) and/ chronic infectious disease 

or condition 

Inability to ambulate Prolonged recumbency Many 

Signs of severe organ or Respiratory: rapid or labored Toxicity testing; 

system involvement breathing, coughing, rales systemic disease 

Cardiovascular: shock, 

hemorrhage, anaphylaxis 

Gastrointestinal: severe 

diarrhea or vomiting 

Peripheral Nervous System: 

flaccid or spastic paralysis 

CNS Signs: circling, 

blindness, dementia, 

convulsion 

Progressive hypothermia Decrease of 4-6oC in body Infectious disease studies; 

temperature in rodents vaccine potency studies 

Moribund or Define with specific clinical Many 

pre-moribund state signs and euthanize when 

reached 
108 C. Review of Proposals 

References 

CCAC (Canadian Council on Animal Care). 1998. CCAC guidelines on choosing 

an appropriate endpoint in experiments using animals for research, teaching, and 

testing. Canadian Council on Animal Care. Ottawa, Canada. 

Carstens E., and O.P.Moberg. 2000. Recognizing pain and distress in laboratory 

animals. ILAR J 41:62-71. 

Dennis M. 2000. Humane endpoints for genetically engineered animal models. ILAR 

J 41:94-98. 

Hendriksen C.F.M., and D.B. Morton, editors. 1999. Humane Endpoints in Animal 

Experiments for Research. In: Proceedings of the International Conference, November 22- 25, 1998, Zeist, The Netherlands. London: Royal Society of Medicine Press 

Limited. 

Hendriksen C.F.M., and B. Steen. Refinement of vaccine potency testing with the 

use of humane endpoints. ILAR J 41:105-113. 

Montgomery, C.A. Oncologic and toxicologic research: alleviation and control of 

pain and distress in laboratory animals. Cancer Bulletin 1990; 42:230-237. 

Morton D.B. 2000. A systematic approach for establishing humane endpoints. ILAR 

J 41:80-86. 

NRC [National Research Council]. 1992. Recognition and Alleviation of Pain and 

distress in Laboratory Animals. National Academy Press, Washington, DC. 

Olfert E.D., and D.L. Godson. 2000. Humane endpoints for infectious disease animal models. ILAR J 41:99-104. 

OECD (Organization for Economic Cooperation and Development). 2000. Guidance 

document on the recognition, assessment, and use of clinical signs as humane 

endpoints for experimental animals used in safety evaluation. Paris, France: Organization for Economic Cooperation and Development. 

OECD (Organization for Economic Cooperation and Development). 1998. Harmonized Integrated Hazard Classification System for Human Health and Environmental 

Effects of Chemical Substances. Paris, France: Organization for Economic Cooperation and Development. 

Sass N. 2000. Humane endpoints and acute toxicity testing. ILAR J 41:114-123. 

Stokes W.S. 2000. Humane Endpoints for Laboratory Animals Used in Toxicity Testing. In: Proceedings of the 3rd World Congress on Alternatives and Animal Use in 

the Life Sciences, Bologna, Italy, August 31-September 2, 1999. New York: Elsevier 

Sciences (Forthcoming). 

Stokes W.S. 2000. Reducing Unrelieved Pain and distress in Laboratory Animals 

Using Humane Endpoints. ILAR J 41:59-61. 
C.2. Protocol Review Criteria 109 

Stokes W.S., and R.N. Hill. 2000. The Role of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in the Evaluation of New 

Toxicological Testing Methods. In: Proceedings of the 3rd World Congress on Alternatives and Animal Use in the Life Sciences, Bologna, Italy, August 31-September 

2, 1999. New York: Elsevier Sciences (Forthcoming). 

Tannenbaum J. 1999. Ethics and pain research in animals. ILAR J 40:97-110. 

Toth L.A. 2000. Defining the moribund condition as an experimental endpoint for 

animal Research. ILAR J 41:72-79. 

UKCCCR [United Kingdom Coordinating Committee on Cancer Research]. 1997. 

Guidelines for the Welfare of Animals in Experimental Neoplasia. London: UKCCCR. 

Wallace J. 2000. Humane endpoints and cancer research. ILAR J 41:87-93. 

C.2.d. Minimization of Pain and Distress 

It is the responsibility of the IACUC to critically evaluate all research protocols for the potential to cause pain or distress and assess the steps that are 

to be taken to enhance animal well-being. 

As required by the PHS Policy and the AWRs, and reiterated in the Guide, 

the IACUC is mandated to review protocols to ensure that pain and distress 

are minimized in laboratory animals. The AWRs stipulate that the IACUC 

determine that the principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain or distress to 

the animal and has provided a written narrative description of the methods 

and sources used to determine that alternatives were not available. Additional guidance from the USDA on this subject is provided in their policies. 

The Guide states that the IACUC should ensure the protocol addresses: 

• appropriate sedation, analgesia, and anesthesia; 

•	 criteria for timely intervention, removal of animals from study, or 

euthanasia if painful or stressful outcomes are anticipated; and 

• details of postprocedural care. 

The protocol must provide adequate information for the IACUC to assess 

the potential animal pain and/or distress resulting from the study and the 

effectiveness of the pain- and distress-relieving agents proposed for use. 

Criteria for re-dosing the animal should also be established. The AV must 

be consulted for any procedure that has the potential to cause more than 

momentary pain or distress. 
110 C. Review of Proposals 

Examples of procedures which the Guide suggests may have the potential 

to cause pain or distress, include: 

• physical restraint, 

• survival surgeries, 

• food or water restriction, 

• death as an endpoint, 

• noxious stimuli, 

• skin or corneal irritancy testing, 

• tumor burdens, 

• intracardiac or orbital sinus blood sampling, and 

• abnormal environmental conditions. 

Assessing Pain and Distress 

Numerous references indicate that both laboratory animals and humans 

receive and process noxious stimuli using similar mechanisms and with 

similar thresholds of awareness. The pain tolerance, or maximum stimulus 

intensity voluntarily accepted, varies between species and between 

individuals of the same species, including humans. Pain typically results 

from stimuli that damage tissue or have the potential to damage tissue. 

An animal’s response to pain is often adaptive to reduce movement to 

minimize reinjury and aid recuperation. However, this response may lead to 

physiological and behavioral changes which impact negatively on both the 

animal’s well-being and the research results. 

Fundamental to the relief of pain is the ability to recognize its clinical signs 

in various species of animals. Due to the inability of animals to verbalize, it 

is essential that animal care staff and researchers receive adequate training 

on how to recognize clinical signs of pain and distress. Tables A, B, and C at 

the end of this section identify some of the indicators. 

According to the NRC report on pain and distress, while there are no 

generally accepted criteria for distress, there are a number of metabolic, 

physiologic and behavioral parameters that are altered in distressed 

animals. These include changes in reproductive performance, elevation in 

glucocorticoid levels and elevation in catecholamine levels. It is necessary 

to use objective assessments, which means choosing appropriate parameters and quantifying observations. Numerous models for scoring pain and 

distress have been published and involve assigning a numeric score to 
C.2. Protocol Review Criteria 111 

observations with the aid of descriptors. It is often useful to start with a 

general set of observations for assessing pain and distress such as change 

in body weight, physical appearance/posture or changes in unprovoked 

and provoked behavior. The assessment system should then be modified 

on a case-by-case basis using specific changes that may be anticipated in 

a particular study. 

Alleviation of Pain and Distress 

Accepted best practices for dealing with the possibility of unrelieved 

pain and distress should be considered and incorporated into protocols 

unless there is a sound scientific rationale for deviation from those practices. The investigator must also provide an assurance that unrelieved pain 

will continue for only the minimum period of time necessary to attain the 

study objectives. 

Protocol methodology should be considered which decreases the potential 

for pain or distress. In addition to thorough searches of the literature, this 

can be done through the careful use of pilot studies to determine earlier 

endpoints or less invasive alternatives. 

Pharmacologic treatment of pain or distress should be given as consistent 

with the type of pain/distress and the needs of the research question. The 

veterinarian must be consulted for all such protocols and should provide 

guidance to investigators and the IACUC. The responses of different species to different anesthetics, analgesics or tranquilizers vary and are not 

fully defined. Often the effects of a given drug have only been examined in 

a single species and definitive information, for example, on cardiovascular 

and respiratory function or on the ability to relieve the perception of noxious 

stimuli, is missing. As a result, dosages have been developed on the basis 

of the amount required to produce cessation of movement when the animal 

is confronted by what is assumed to be a painful manipulation, in conjunction with an adequate recovery. Because of the imprecise nature of the 

studies, dosage ranges are often quite wide, requiring a very conservative 

approach to their use. The use of drug mixtures further complicates the 

choice of an adequate dose. Numerous reference texts exist and IACUCs 

may request that the veterinarian prepare current charts of recommended 

doses as an institutional resource for investigators. 

Non-pharmacologic treatments should also be employed. This may include 

special housing considerations, dietary and other environmental enrichments, adjustments and careful supportive care. 
112 C. Review of Proposals 

Summary 

It is the responsibility of the investigator to show she or he has considered 

all the options for minimizing pain and distress that do not compromise the 

scientific validity of the experiment. The committee’s deliberations regarding the management of potential pain and distress in a protocol should be 

documented. Personnel should be trained in pain and distress management. The IACUC should ensure that there is a mechanism in place for 

prompt reporting of sick animals to the veterinary staff. 

C.2.d. Table A. Definitions of Terminology Related to Pain and Distress 

Analgesia A complete loss of sensitivity to pain. 

Anesthesia A total loss of sensation in a part of or in the entire body. 

Distress An aversive state in which an animal is unable to adapt completely 

to stressors and the resulting stress and shows maladaptive behavior. 

Pain An unpleasant sensory or emotional experience associated with 

actual or potential tissue damage. 

Sedation A state characterized by decreased awareness of surroundings, 

relaxation, and sleepiness. Analgesia is not present. 

Tranquilization A state of mental calming, decreased response to environmental 

stimuli, and muscle relaxation. No sleep, analgesia or anesthesia 

is present, even at increased dosage. 

From: American College of Laboratory Animal Medicine. 1997. Anesthesia and Analgesia in Laboratory Animals. D.F. Kohn, S.K. Wixson, W.J. White and G.J. Benson, eds. Academic Press. 

C.2.d. Table B. Signs of Acute Pain 

Sign Explanation 

Guarding Attempting to protect, move away, or bite


Vocalization Crying out when palpated or forced to use affected area


Mutilation Licking, biting, scratching, shaking, or rubbing


Restlessness Pacing, lying down and getting up, or shifting weight


Sweating In species that sweat (horses)


Recumbency Unusual length of time


Depression Reluctance to move or difficulty in rising


Abnormal appearance Head down, tucked abdomen, hunched, facial distortion, or pallor


Reprinted with permission from SOMA, 1987. Soma, L.R. 1987. Assessment of animal pain in 

experimental animals. Lab Anim Sci 37:71-74. Reprinted with permission from Recognition 

and Alleviation of Pain and Distress in Laboratory Animals. Committee on Pain and Distress in 

Laboratory Animals, Institute of Laboratory Animal Resources, Commission on Life Sciences, 

National Research Council. National Academy Press, Washington, DC. 1992. 
C.2. Protocol Review Criteria 113 

C.2.d. Table C. Signs, Degree and Length of Surgically 

Produced Pain* 

Surgical Site Signs of Pain Degree of Pain Length of Pain 

Head, eye, Attempts to rub or scratch, Moderate to high Intermittent 

ear, mouth self-mutilation, shaking, to continual 

reluctance to eat, drink, or 

swallow, reluctance to move 

Rectal area Rubbing, licking, biting, Moderate to high Intermittent 

abnormal bowel movement to continual 

or excretory behavior 

Bones Reluctance to move, Moderate to high: Intermittent 

lameness, abnormal upper part of axial 

posture, guarding, skeleton (humerus, 

licking, self-mutilation femur) especially 

painful 

Abdomen Abnormal posture (hunched), Not obvious to Short 

anorexia, guarding moderate 

Thorax Reluctance to move, Sternal approach, Continual 

respiratory changes (rapid, high; lateral 

shallow), depression approach, slight 

to moderate 

Spine, cervical Abnormal posture of head Moderate to severe Continual 

and neck, reluctance to 

move, abnormal gait— 

“walking on eggs” 

Spine, thoracic Few signs, often Slight Short 

or lumbar moving immediately 

*Based on observations of dogs. 

Reprinted with permission from Recognition and Alleviation of Pain and Distress in Laboratory 

Animals. Committee on Pain and Distress in Laboratory Animals, Institute of Laboratory Animal 

Resources, Commission on Life Sciences, National Research Council. National Academy Press, 

Washington, DC. 1992. 
114 C. Review of Proposals 

References 

American College of Laboratory Animal Medicine. 1997. Anesthesia and Analgesia 

in Laboratory Animals. D.F. Kohn, S.K. Wixson, W.J. White and G.J. Benson, eds. 

Academic Press. 

National Research Council. 2000. Definition of Pain and Distress and Reporting 

Requirements for Laboratory Animals. 

Wolfensohn, S. and M. Lloyd, 1998. Handbook of Laboratory Animal Management 

and Welfare, Second Edition. Blackwell Science, Oxford. 334 pp. 

Recognition and Alleviation of Pain and Distress in Laboratory Animals. NRC. 1992. 

C.2.e. Personnel Qualifications 

In evaluating proposed research projects, the PHS Policy and the AWRs 

require the IACUC to assess whether personnel conducting procedures are 

appropriately qualified and trained in those procedures (IV.C.1.f and 

2.31(d)(1)(viii)). A similar requirement can be found on page 10 of the Guide 

and in U.S. Government Principle VIII (see Appendix F). 

Developing Guidelines 

To facilitate evaluation of personnel qualifications and training during protocol review, each IACUC should develop a list of items to be assessed as 

well as a list of classifications of personnel required to participate in such 

training. This could be a list of qualifications and training items specific to 

protocols according to procedures and or manipulations proposed or the 

list could be broad enough to cover all aspects of the institution’s training 

requirements (see Section A.4). 

A procedure specific checklist might include: 

• proficiency in handling specific specie(s), 

• proficiency in pain-relieving methods, 

• proficiency in surgical manipulations, 

• proficiency in aseptic techniques, 

• proficiency in pain management, 

• proficiency in euthanasia, 

• proficiency in pre- and post-operative care, 

• Drug Enforcement Administration (DEA) license, and 

• approval by safety office. 
C.2. Protocol Review Criteria 115 

A checklist of institutional requirements that need to be satisfied as a 

component of protocol review might include the following in addition to 

those above: 

• completion of occupational health and safety risk assessment, 

• demonstrated knowledge of relevant rules and regulations, 

• enrollment in occupational health and safety program, 

• attendance at compliance training session, and 

• viewing of safety training video. 

Classifications of employees whose qualifications and training may require assessment include: 

• investigators, 

• research technicians, 

• animal husbandry personnel, and 

• veterinarian and veterinary technicians. 

An important decision to be made by the IACUC is the level of training 

required of an investigator not actually involved in the day-to-day manipulation and care of the animals. If the investigator is responsible for the 

research activity and the animals involved, should she or he demonstrate 

proficiency in the areas indicated above? Is the investigator responsible 

for training personnel in the lab? If yes, should she or he demonstrate 

proficiency in those areas? An IACUC policy on this issue will prevent 

conflict later. 

Evaluating Qualifications and Training 

To prevent problems related to assessment of qualifications and training 

during protocol review, it is helpful if the IACUC determines any training 

needs during the protocol development and veterinary consultation. Discussion of new techniques, procedures, or manipulations at this time can 

provide the impetus for a training opportunity for both the veterinary staff 

and the research staff with demonstrated proficiency completed prior to 

protocol review. This training experience should be so noted in the protocol 

or otherwise documented. 

Maintaining a database of all participants in the facility’s training program 

who use laboratory animals will facilitate assessment of qualifications and 

training. With such a database, preliminary evaluation of an individual’s 
116 C. Review of Proposals 

expertise can be an administrative task performed by the IACUC or staff 

assigned to assist with managing the animal care program. If a deficiency 

is noted, a follow-up memo can be sent to the investigator stating that 

protocol review is pending until training requirements have been completed. 

IACUCs should note that high morbidity or mortality rates or requests for 

more animals than originally planned may indicate a training opportunity 

and should be followed up in the context of the relevant protocol, either 

immediately or during the semiannual review. 

Evaluating the qualifications and training of new personnel or those 

proposing to use new techniques, procedures, or manipulations will necessitate another approach by the IACUC. 

New Personnel 

One way to manage the training of new personnel is to initiate an IACUC 

policy that no protocol will be reviewed until training requirements have 

been satisfied. Such training would need to incorporate all institutional requirements as well as those specific to the work expectations of the individual, and might include those listed above. 

New Techniques, Procedures or Manipulations 

When an investigator proposes new techniques, procedures, or manipulations, the IACUC must assure itself that the personnel are qualified to 

perform the work. If no training module on a particular technique, procedure, or manipulation exists, it is possible that the most closely aligned 

existing module can be used. If the personnel have not demonstrated 

proficiency through one of the training modules (see Section A.4), the IACUC 

can consider the following options: 

•	 The IACUC may mandate that the individual(s) complete pertinent training before the protocol can be reviewed. This assumes the IACUC has 

a policy that stipulates adequate qualifications and training as a 

condition of protocol review. 

•	 If no relevant training module exists, a possible course of action would 

be to stipulate that the veterinarian supervise the new technique, 

procedure, or manipulation pending certification of training or demonstration of proficiency. If there are no in-house personnel with 

the necessary expertise, the IACUC can seek a consultant for advice 
C.2. Protocol Review Criteria 117 

and training. This should not be viewed as a confrontational event, but 

rather one with educational value for both the veterinarian and the 

research staff. Documentation of this training experience should be 

made in the IACUC files or database. 

In summary, evaluation of personnel qualifications and training is an essential component of the review of animal use protocols to ensure the humane 

care and use of laboratory animals. The challenge to IACUCs is to perform 

this evaluation in an efficient, consistent and uniform manner. 

C.2.f. Veterinary Review and Consultation 

Each IACUC is required by the AWRs and the PHS Policy to have as one 

of its members a Doctor of Veterinary Medicine with direct or delegated 

program authority and responsibility for animal activities at the institution. 

The AWRs and the PHS Policy require that the veterinarian be trained 

or experienced in laboratory animal science and medicine for the species 

used at the institution; the Guide recommends the IACUC veterinarian be 

American College of Laboratory Animal Medicine (ACLAM) certified or have 

equivalent experience. 

The Report of the American College of Laboratory Animal Medicine on 

Adequate Veterinary Care in Research, Testing and Teaching (1996) states: 

The veterinarian must be involved in the review and approval 

of all animal care and use in the institutional program. This 

includes advising on the design and performance of experiments using animals as related to model selection, collection and analysis of samples and data from animals, and 

methods andtechniques proposed or in use. This responsibility is usually shared with investigators, the IACUC, and 

external peer reviewers. 
118 C. Review of Proposals 

The veterinarian plays a key role in IACUC protocol review, as described 

below. 

Reviewing Animal Use Protocols 

The veterinarian can integrate his or her experience and training with that 

of the investigator and advise the investigator on selection of species, 

their sex, age and/or size. The veterinarian can assess the ability of 

the animal facility and its staff to support the proposed species and associated procedures. 

When the selection criteria have been established, the veterinarian can 

assist the IACUC in reviewing the proposed procedures and techniques 

appropriate to the goals of the study. 

Reviewing Protocols for Potential Pain and Distress 

The AWRs require that investigators proposing procedures that may 

cause more than momentary or slight pain or distress to the animals will 

consult with the AV or his or her designee. Similarly, the veterinarian has implicit responsibilities outlined in the AWRs to assess the potential for pain 

and distress that might be associated with the proposed animal activities, and to recommend the use of pain alleviating drugs, whenever 

possible, to counteract those conditions. 

Reviewing Protocols Involving Surgery 

The veterinarian can ensure that appropriate provision is made for preoperative and post-operative care of the animals in accordance with 

established veterinary medical and nursing practices. As noted in the AWRs 

and the Guide, all survival surgery should be performed using aseptic 

procedures, including the use of surgical gloves, masks, sterile instruments, 

and aseptic techniques. 

The veterinarian may provide the IACUC with assessment of the following: 

•	 preparation of the animal for the surgical intervention, to include the 

use of pre-anesthetic drugs where indicated, and appropriate 

anesthetic agents; 

•	 that the individual(s) performing the surgery has adequate experience or training for the specific procedures outlined in the study; 
C.2. Protocol Review Criteria 119 

• that aseptic techniques are appropriate for the procedure; and 

•	 that adequate post-operative care, to include post-operative analgesics where indicated, is provided. 

Reviewing Protocols To Ensure Humane Euthanasia of Animals 

The American Veterinary Medical Association (AVMA) provides guidance 

on the most humane methods to be used for euthanasia of animals, to 

include those used in research, testing and training. Their most recent 

recommendations are contained in the “2000 Report of the AVMA Panel on 

Euthanasia” (JAVMA Vol. 218, No. 5, pages 669-696). The veterinarian on 

the IACUC, using that publication or subsequent editions as the principal 

reference, can assess the investigator’s proposed method of euthanasia. 

After Protocol Review and Approval 

Following IACUC approval of protocols, the veterinarian is in a position, 

through periodic visits to the animal facility and animal activity areas, to 

observe and evaluate animal well-being and decide whether the animal 

activities are being conducted in accordance with the conditions described 

or referenced in the protocol. The veterinarian, by virtue of training and 

experience, is able to serve in advocacy, oversight, and intervention roles 

that are distinct and unique among the IACUC members and research staff. 

Checklist 

Some Examples of the Veterinarian’s Responsibilities 

During Protocol Development and Review* 

• Choice and use of appropriate analgesics/anesthetics 

•	 Verification of appropriate drug dosages, route of administration and 

choice of agent 

• Assistance in selection of appropriate animal model 

•	 Identification of refinement initiatives to ensure that manipulations 

have a minimal impact on animal welfare 

• Oversight of aseptic surgery and peri-operative care 

•	 Oversight of animal health and husbandry pertinent to the protocol and 

the entire colony 
120 C. Review of Proposals 

•	 Identification of possible iatrogenic complications of model and 

procedures selected 

•	 Ensuring there are appropriate remediation efforts for iatrogenic 

complications 

•	 Serving as an occupational health and safety (including zoonoses) 

resource 

• Serving as a regulatory compliance resource 

•	 Assistance in identifying appropriate endpoints and in ensuring 

humane euthanasia. 

*This checklist is not all-inclusive; rather it provides examples of the veterinarian’s responsi	

bilities, which may vary with each proposal. 
C.3. Other Protocol Review Considerations 

C.3.a. Agricultural Research 

Farm animals are used in a variety of research contexts, including: 

• vaccine trials, 

• studies of basic biological processes, 

• studies of pharmacokinetics and organ transplantation, and 

•	 studies of nutritional, breeding and management methods to increase 

the supply and quality of food and fiber. 

Unlike typical laboratory animals, farm animals used for research and teaching may be housed in many different kinds of environments, ranging from 

traditional laboratory environments to enclosed or extensive farm settings. 

Because of these factors, as well as the regulatory complexity surrounding 

farm animal oversight, determining standards for the evaluation of research, 

teaching, and testing using farm animals is more complicated than for other 

laboratory animals. 

Applicability of PHS Policy and the AWRs 

Farm animals used for improving animal nutrition, breeding, management, 

production efficiency, or the quality of food and fiber are specifically 

excluded from the definition of “animal” in the AWA. The PHS Policy applies 

to vertebrates used in research, research training and biological testing, 

funded by the PHS. Some Assurances extend coverage of the PHS Policy 

to all animal activities at an institution. Hence, farm animals used in research, teaching or testing may be covered by the PHS Policy and the AWRs. 

Farm animals used in agricultural research may not be covered by either. 

OLAW advises institutions that uniform and consistent standards are an 

essential ingredient in a quality animal care and use program. Public perception of a potential double standard should also be considered. 

121 
122 C. Review of Proposals 

Standards for Evaluation of Agricultural Animal Research and Teaching 

In 1988, a consortium of organizations and agencies developed guidelines 

for the care and use of farm animals, the Guide for the Care and Use of 

Agricultural Animals in Agricultural Research and Teaching (known as the 

Ag Guide). The Ag Guide, revised in 1999, was written to aid IACUCs in the 

evaluation of projects involving farm animal research or teaching “for which 

the scientific objectives are to improve understanding of the animal’s use in 

production agriculture and that may require a simulated or actual production setting.” The Ag Guide is comprised of overview chapters covering 

institutional policies, veterinary care, husbandry, and physical plant, as well 

as specific species chapters for horses, cattle, poultry, and sheep and goats. 

Adoption of the Ag Guide by an institution is voluntary, although the USDA 

endorses it as a basis for animal care review of USDA competitive grant 

submissions and projects receiving experiment station funding. 

This dual system of oversight for research and agricultural animals can pose 

challenges for IACUCs. In order to be relevant to commercial production, 

agricultural research must often be conducted under conditions similar to 

those found on commercial farms. However, there are practices that are 

common in commercial agriculture that would not ordinarily be permitted 

under the regulations governing research; for example, castrating young 

animals without anesthesia or closely confining animals in cages or stalls 

throughout the production cycle. But determining whether a particular protocol is agricultural or biomedical research, and which standards should be 

applied, is not always straightforward. For example, studies of basic biological processes in farm animals may benefit food and fiber production, 

but may also have human health implications. USDA Policy 26 provides 

some clarification, stating that farm animals used to manufacture and test 

biologicals for nonagricultural or nonproduction animals, or for humans, are 

considered research animals and thus are regulated under the AWA. But 

gray areas remain, and IACUCs need to consider animal welfare, protocol 

requirements, and research or teaching goals when setting standards. 

Recently, there has been recognition that some melding of these different 

guidelines and standards may be necessary and appropriate. For example, 

the Guide, while intended to apply only to farm animals used for research 

purposes, recognizes that such animals may sometimes be housed in farm 

settings, and recommends the Ag Guide as a useful resource in such situations. And although USDA-APHIS decided to regulate farm animals used 

in research in 1991, they did not develop specific standards; instead, they 

adopted the Ag Guide and the Guide as guidance documents (Policy 29). 
C.3. Other Protocol Review Considerations 123 

AAALAC also uses both the Guide and Ag Guide as reference documents 

for the accreditation of farm animal facilities and programs. Thus, the use of 

a performance-based approach is desirable. 

Review of Protocols and Facilities 

Institutions employ a number of different approaches to reviewing activities 

involving animals used for agricultural research and teaching. Some have 

a single committee that reviews all protocols, while others have a subcommittee or even a separate committee that reviews agricultural animal 

research protocols. (As applicable, committees must comply with the membership and review procedures required by the PHS Policy and the AWRs.) 

There are benefits and limitations associated with each of these approaches. 

However, what is most important is that the institution ensures uniform 

and high-quality oversight of all research, teaching, and testing activities 

involving animals, regardless of the species or the type of research 

being conducted. 

For thorough oversight of agricultural animal care and use, it is particularly 

important that there be agricultural expertise on the IACUC. The Ag Guide 

suggests that the IACUC include, among other members: 

•	 a scientist from the institution with experience in agricultural research 

or teaching involving agricultural animals; 

•	 an animal, dairy or poultry scientist who has training and experience 

in the management of agricultural animals; and 

•	 a veterinarian who has training and experience in agricultural animal 

medicine and who is licensed or eligible to be licensed to practice 

veterinary medicine. 

There are unusual aspects of agricultural research that deserve careful 

consideration by IACUCs. As mentioned previously, there are certain 

husbandry practices common on commercial farms that have the potential 

to cause pain or distress that would not ordinarily be permitted under the 

regulations governing research. The Ag Guide recommends that IACUCs 

review these procedures, as well as husbandry conditions that do not meet 

the standards outlined in the Ag Guide, even if they are considered normal 

practice. Another unusual aspect of agricultural research is that the animals 

may be killed and marketed for human food at the end of studies, which 

means that there are special considerations with respect to avoiding residues from therapeutics and other drugs. 
124 C. Review of Proposals 

The extent of oversight is another issue that IACUCs need to address. 

At institutions with agricultural colleges, there may be multiple lines of 

authority for animal facilities and animal ownership. In addition, animals 

may be housed at off-site facilities at some distance from the main unit. The 

IACUC needs to ensure that there is adequate oversight of all animals 

under approved protocols. Agricultural and veterinary extension faculty 

may also conduct research or teach using privately owned animals on 

private farms, and the IACUC should consider whether or not these activities need to be covered by protocols. 

Finally, the facilities in which agricultural animals are housed are often older 

than typical laboratory animal facilities. Because many of these facilities are 

semi-enclosed or open, there may be problems with rodent control and 

some other aspects of maintenance. Recordkeeping in agricultural animal 

facilities may be less complete than that required in conventional lab animal 

facilities. The IACUC should be aware that there can and should be a high 

standard of animal care even in modest facilities. The development and 

implementation of standard operating procedures for these facilities can 

help to ensure a consistent standard of animal care. 

Conclusion 

Although not always required by law, the monitoring of food and fiber 

animal research and teaching activities can significantly benefit an institution by improving the overall quality of the animal care program. Because 

agricultural research often has the improvement of food or fiber production 

as an endpoint, standards may differ from those for research animals. This 

does not mean, however, that different ethical standards should be used by 

an IACUC in considering the use and care of farm animals used for food 

and fiber research. Experimental goals and animal welfare should both be 

considered when evaluating the use and treatment of these animals. 

References 

Curtis, S.E. 1994. Commentary: Farm animal use in biomedical sciences—melding 

the guidelines. ILAR News 36:35-39. 

FASS (Federation of Animal Science Societies). 1999. Guide for the Care and Use of 

Agricultural Animals in Agricultural Research and Teaching. Savoy, IL: FASS. 

Joiner, G. 1990. Agricultural animal care review. AWIC Newsletter, Volume 1. 

Mench, J.A., S. J. Mayer, and L. Kruslisch. 1992. The Well-Being of Agricultural 

Animals in Biomedical and Agricultural Research. Bethesda, MD: Scientists Center 

for Animal Welfare. 
C.3. Other Protocol Review Considerations 125 

Stricklin, W.R. and J.A. Mench. 1994. Oversight of the use of agricultural animals in 

university teaching and research. ILAR News 36:9-14. 

Swanson, J.C. 1998. Oversight of farm animals in research. Lab Animal 27, 28-31. 

Tillman, P. 1994. Integrating agricultural and biomedical research policies: conflicts 

and opportunities. ILAR News 36:29-35. 

AAALAC International Position Statement on “Farm Animals”. 

C.3.b. Antibody Production 

Antibodies are important tools for research. Depending on research needs 

antibodies may be produced by polyclonal or monoclonal technique. Each 

technique requires that specific issues be addressed in animal protocols. 

IACUCs should ensure adequate training of personnel in the use of proper 

technique when any method of immunization is proposed. The advantages 

of a centralized service utilizing skilled technicians to meet multiple research 

groups’ needs for polyclonal and monoclonal antibodies is another refinement which may enhance animal welfare in larger research programs. There 

are also many commercial sources of antibodies made to order. 

A good resource is “Information Resources for Adjuvants and Antibody 

Production: Comparisons and Alternative Technologies.” AWIC Resource 

Series, No. 3. August 1997. Call Number: aHV4701.A94no.3. ISBN 

090076791X. The document includes over 500 bibliographic citations 

regarding adjuvants and antibody production methods compiled from 

scientific journals, proceedings and newsletters. A company/institute listing of suppliers of antibodies and antibody production products is included. 

Emphasis is placed on citing comparative studies and research into 

alternative methods. 

Polyclonal Antibody Production 

Injection of an immunogen (e.g., protein, virus, bacterium) into an animal 

produces a humoral response, which induces the production of a population of heterogeneous antibodies, with varying specificities toward different 

molecular regions (epitopes) of the immunogen. Two types of lymphocytes 

(T cells, derived from the thymus, and B cells, derived from marrow) are 

responsible for the production of polyclonal antibodies. Polyclonal antibodies produced in response to infection can be effective in recognizing and 

eliminating foreign material, but the heterogenicity of the product limits its 

use in research and industry. 
126 C. Review of Proposals 

Adjuvants 

To increase the immune response, the immunogen may be combined with 

an adjuvant. Adjuvants stimulate the rapid and sustained production of high 

titers of antibodies with high avidity. Adjuvants may facilitate the immune 

response through three basic mechanisms: 

•	 Adjuvants may serve as a depot for the antigen, which should increase 

the duration of antigen exposure and the antibody response. 

• Adjuvants may stimulate immune cells. 

•	 Adjuvants may enhance macrophage phagocytosis after binding the 

antigen as a particulate (a carrier/vehicle function). 

The use of adjuvants is required for many antigens which by themselves 

are weakly immunogenic. Adjuvant selection remains largely empirical. 

Antigens that are easily purified or available in large quantities may be good 

choices for starting with the least inflammatory adjuvants for immunization. 

Should antibody response not be suitable, a gradual increase in the inflammatory level of the adjuvant would then be warranted. 

The choice of the appropriate adjuvant is important from both the aspect of 

the end result (high antibody response) and the welfare of the immunized 

animal. Many of the adjuvants have the capacity to cause inflammation, 

tissue necrosis and pain in animals. A major charge to investigators is to 

minimize animal use and discomfort. 

Freund’s incomplete adjuvant (IFA) is a water/oil emulsion containing 

immunogen, paraffin oil and an emulsifying agent. Addition of killed mycobacteria to the oil phase (Freund’s complete adjuvant, CFA) enhances the 

immune response. Multiple exposures to CFA will cause severe hypersensitivity reactions. The use of CFA can be painful and alternative adjuvants should be considered. Abscesses, granulomas and tissue sloughs 

may occur at injection sites. However, a recent report (Halliday) suggests 

that when the NIH intramural guidelines are meticulously followed, assuring aseptic technique and adding the judicious use of chemical sedation, 

the use of CFA for immunization is a humane procedure. Undesirable 

and painful side effects must be minimized or eliminated by careful preparation of inoculum, the use of appropriate routes of administration, 

adequate separation of injection sites, and the use of a small amount of 

inoculum per site. 
C.3. Other Protocol Review Considerations 127 

Because of the severity of the secondary immune response to mycobacterium in CFA, IFA must be used with booster antigen administrations in cases 

where CFA has been used in the initial injection. 

For many years CFA was the only effective adjuvant, but this is no longer 

true. Other adjuvants are available as alternatives and may be suitable for 

use in an investigator’s experiments. 

Route of Injection 

The range of recommendations for routes and sites of administration of 

antigen-adjuvants preparations, volumes per site and number of sites per 

animal for different species vary in the literature and institutional guidelines. 

Particularly with the use of CFA, it is important to note that the severity of 

potentially painful inflammatory reactions may be minimized by injection of 

a small volume of inoculum per site and the use of multiple injection sites 

when appropriate. Injection sites must be sufficiently separated to prohibit 

coalescing of the inflammatory lesions. 

Using multiple sites for immunization also provides more foci for antigen 

presentation and the involvement of more lymph nodes. Intradermal and 

subcutaneous routes are commonly used to take advantage of antigen-processing dendritic cells present within the dermis. Hair should be 

clipped from intradermal and subcutaneous injection sites, and the site 

should be aseptically prepared with betadine or nolvasan scrub followed by 

alcohol or other appropriate antiseptics. The following recommendations 

apply primarily to antigen solutions in CFA or IFA. Volumes ranging from 

0.05 ml to 0.10 ml per site have been recommended for intradermal injections in rabbits. A total of five intradermal sites has been recommended. 

Because intradermal sites ulcerate with FCA, sterile inocula must be used 

and the site must be properly disinfected to prevent secondary bacterial 

infection. Subcutaneous injection volumes in the rabbit vary from recommendations of 0.10 ml to 0.25 ml to 0.40 ml per site. Number of sites 

recommended varies from 4 to 10. 

Footpad injections in rabbits are prohibited. Where scientific justification is 

provided, footpad injections may be permitted in rodents, but only in one 

hind foot, and with the animals housed on soft bedding. Suggested maximum injection volumes can range from 0.01 to 0.05 for mice and 0.10 ml 

for rats. The need for footpad injections must be critically evaluated by the 

IACUC before approval. 
128 C. Review of Proposals 

Sometimes direct inoculation into lymph nodes, such as the popliteal lymph 

node, is used. With practice these nodes often can be palpated and the 

injection performed percutaneously. 

Intramuscular injections, usually made in the biceps femoris or quadriceps 

muscle mass, generally are lower volumes of 0.25 ml to 0.20 –0.40 ml. Care 

must be exercised to avoid adjacent nerves and blood vessels as well as 

fascial planes when injecting into a muscle bundle. Disagreement exists as 

to the appropriateness of intramuscular injection of CFA. The intramuscular 

route of injection is recommended in some institutional guidelines and specifically discouraged in other guidelines. Intramuscular injection is generally 

not recommended in rodents because of limited muscle mass. 

For TiterMax®, intradermal, subcutaneous, and intramuscular routes are 

recommended with volumes per injection site ranging from 0.01 to 0.25 ml 

in small and large animals. For Ribi®, intradermal, subcutaneous and intramuscular routes are recommended with volumes per injection site ranging 

from 0.05 to 0.50 in small and large animals. 

Monoclonal Antibody Production 

Monoclonal antibodies (mAbs) are homogeneous because they are produced by hybrid cells derived from a single antigen-stimulated B cell. The 

production of mAbs involves two phases. In the first phase an animal 

(usually a mouse) is immunized with the antigen of interest. Immunization 

of the antigen is often performed with an adjuvant, as discussed above. 

Splenocytes are harvested from the responding animal, and are fused with 

a myeloma cell line for in vitro propagation. 

Before the immunization protocol begins, the methodology for detecting 

the specific antibody of interest in the mouse sera and tissue culture supernatants is developed. Otherwise, significant time and animal resources 

may be wasted later in the mAb-developing phase. Test bleeds should 

be performed in order to determine if the mice are responding to the immunizations. Most immunologically based assays for determining if the 

desired antibodies are being produced require less than 10 microliters of 

mouse serum. Once an appropriate response has been confirmed the mice 

should be boosted again and typically after three days from the boost the 

mice should be euthanized and spleens harvested. 

The second phase is production of adequate quantities of mAb for a project 

or analysis. There are two major methods: in vitro and the ascites method. 
C.3. Other Protocol Review Considerations 129 

The ascites method has been one of the most popular means for producing 

large quantities of highly concentrated monoclonal antibodies since its 

inception in 1972. However, improved techniques and culture media 

have demonstrated that mAbs can be produced by in vitro techniques at a 

quality and concentration that are similar to that of ascites. The National 

Research Council’s report on Monoclonal Antibody Production specifically 

states “in vitro methods for the production of monoclonal antibodies should 

be adopted as a routine method unless there is a clear reason why they 

cannot be used...”. In accordance with the PHS Policy and the Guide, 

alternatives to the use of animals (in vitro techniques) for the production of 

mAbs must be considered in place of the ascites method. (See the Office of 

Extramural Research Guidance concerning the Production of Monoclonal 

Antibodies in Animals, NIH Guide for Grants and Contracts, Notice OD-00-

019, 2/3/2000, and the 11/17/97 OPRR Dear Colleague letter on Production of mABs Using Mouse Ascites Method). 

The ascites method should only be used after in vitro failure of each cell line 

has been demonstrated, or other adequate justification is provided. Analysis of individual cell lines is necessary because the production performance 

of each hybridoma cell line grown in vitro is highly variable. Despite this 

variability, work performed by Petrie indicates that at least 90% of all hybridomas that are placed on in vitro production protocols will yield adequate 

amounts of high quality mAbs. 

Several resources for the in vitro production of mAb are available. Some 

institutions have core facilities that may provide an in vitro mAb production 

service. The NIH also sponsors a national cell culture core facility (National 

Cell Culture Center, Minneapolis, MN; http://www.nccc.com). 

References 

In Vitro mAb Production References 

Jackson, L.R., B.A. Trudel, and N.S. Lipman. 1999, Small Scale Monoclonal Antibody Production in Vitro; Methods and Resources. Lab Animal 28(3):38-50. 

Alternatives in Monoclonal Antibody Production, 1998, The Johns Hopkins Center 

for Alternatives to Animal Testing (CAAT) and National Center for Research Resources 

(NCRR) Workshop. 

Schulhof, J. (ed). 1999. Small-Scale Monoclonal Antibody Production, special 

edition Lab Animal Autumn 1999. 
130 C. Review of Proposals 

Monoclonal Antibody References 

Kohler G., and C. Milstein.1975. Continuous culture of fused cells secreting 

antibody of predefined specificity. Nature 256:495-497. 

Heidel J. 1997. Monoclonal Antibody Production in Gas-permeable Tissue Culture 

Bags Using Serum free Media. Center for Alternative to Animal Testing: Alternatives 

in Monoclonal Antibody Production, 8:18-20. 

Jackson L.R., L. J. Trudel, J.G. Fox, and N.S. Lipman. 1996. Evaluation of hollow 

fiber bioreactors as an alternative to murine ascites production for small scale 

monoclonal antibody production. J Immunol Methods 189: 217-231. 

OPRR Reports, 11/17/97, Number 98-01 Animal Welfare, Production of Monoclonal 

Antibodies Using Mouse Ascites Method. 

Peterson N., and J. Peavey. 1998. Practical applications of in vitro monoclonal 

antibody production. Contemporary Topics Lab Animal Science 37:61-66. 

Monoclonal Antibody Production. 1999. National Academy Press, Washington, DC. 

Jackson L., L. Trudel, J. Fox, and N. Lipman. 1999. Monoclonal antibody production 

in murine ascites. I. Clinical and pathologic features. Lab Animal Science 49:70-80. 

NIH Guide for Grants and Contracts. Notice OD-00-019, 2/3/00. 

Polyclonal Antibody References 

NIH’s ARAC Guidelines: Recommendations for Consideration in the Research Use 

of Inflammatory Agents. Adopted by full Committee of the NIHARC on 8/13/86. 

Reapproved - 5/8/96. 

Halliday, L.C. et al. 2000. Physiologic and Behavioral Assessment of Rabbits Immunized with Freund’s Complete Adjuvant. Contemporary Topics 39(5):8-13. 

Jackson, J.R. and J.G. Fox. 1995. Institutional Policies and Guidelines on Adjuvants 

and Antibody Production. ILAR Journal 37(3):141-152. 

Sigel, M.B., Y.N. Sinha and W.P. VanderLaan. 1983. Production of antibodies by 

inoculation into lymph nodes. Methods Enzymol 93:3-12. 

C.3.c. Breeding Colonies 

Investigators maintain breeding colonies for a variety of reasons. A breeding colony may be required for an established animal model because: 

• the animal model is not commercially available, 

•	 young animals have very specific age or weight requirements that 

cannot be fulfilled by a commercial breeding colony, or 

•	 physiological status of the mutant animal is too severely affected for 

it to survive shipment. 
C.3. Other Protocol Review Considerations 131 

Investigators developing a new spontaneous or induced mutant animal 

model need to maintain their own breeding colony because there is no 

alternative source for this mutant. While trying to establish a breeding colony 

for a new mutant model, the investigator is also simultaneously working 

to determine phenotype, to identify affected physiological system(s), and 

define inheritance pattern. 

To review standard operating procedures for breeding colonies, the IACUC 

will need information about colony management. Examples of necessary 

information include: 

• number of breeders and number of young per cage, 

•	 breeding system including number of females per male or continuous 

versus interrupted mating, 

• weaning age, 

• separation of animals at weaning, and 

• methods for identification of individual animals. 

Large numbers of animals may be required to maintain a breeding colony. 

The exact number of animals can only be approximated because it is 

impossible to predict in advance the exact number and sex of offspring. 

The estimated number of animals should clearly distinguish between: 

• breeders, 

•	 young that cannot be used in experiments because they are of the 

wrong genotype or sex, and 

• animals that will be subject to experimental manipulations. 

Colony management practices should be briefly described in the investigator’s animal protocol, and justification provided for departure from 

standard institutional practices. 

Determining which animals to include in the estimated number of animals 

on an animal protocol can be challenging to the investigator and the IACUC 

in the absence of IACUC-developed guidelines. The estimated number of 

animals that are kept for breeding purposes and not subject to any experimental manipulations should be part of the animal protocol. 

Studies involving genetic analysis are animal intensive. Genetic analysis 

can involve determining if a single gene has dominant or recessive inheritance, identifying different genes involved in a quantitative (polygenic) trait, 
132 C. Review of Proposals 

or fine mapping to determine chromosomal location of a mutant gene. 

It is possible for the investigator to estimate the number of animals 

required, but difficult for the IACUC to evaluate this estimate in the absence 

of experience. 

Up to 1200 mice are required to map a single gene with recessive inheritance and full penetrance, and have adequate numbers of progeny for 

developmental studies, phenotyping and linkage analysis. This number 

assumes a breeding colony of 10 to 12 pair matings with a 6- to 8-month 

reproductive lifespan, around 90% productive matings, replacement of 

breeders, and no unusual mutant infertility or mortality. 

Up to 1100 mice are required for quantitative trait loci analysis using analysis of F2 progeny. The number assumes small breeding colonies of two 

inbred parental strains (4 to 6 pairs) and two reciprocal F1 hybrids (2 to 4 

pairs), no unusual infertility, replacement of breeders at 6- to 8-month intervals, and generation of between 500 and 1000 F2 mice for genotyping. 

Up to 750 mice are required to construct a congenic strain using “speed’” 

congenic genotyping methods. This number assumes a breeding colony of 

10 to 12 breeding pairs, replacement of breeders, and progeny for phenotyping and genetic linkage. If the homozygous mutant does not breed and 

the congenic strain must be developed using intercross matings, the estimated number of mice increases to 1,200. 

After founder transgenic or ‘knock-out’ mice have been identified, between 

80 and 100 mice may be needed to maintain and characterize a line. The 

number assumes up to five breeder pairs per line, breeder replacement, no 

unusual infertility and adequate numbers of weanlings for genotyping and 

phenotyping characterization. 

If a study requires fertilized one-cell eggs, embryos or fetuses, the protocol 

should indicate the number of eggs, embryos or fetuses that are required 

for proposed studies. The estimated number of experimental animals may 

be limited to the number of female animals that are mated and euthanized 

or surgically manipulated to collect the required eggs, embryos or fetuses. 

In this situation, males might be listed as breeders if they are not subject to 

any experimental manipulation. 

If a suckling animal will be subject to any manipulation, such as thymectomy, toe clip or ear notch for identification, tail tip excision for genotyping, 

or behavioral tests, the estimated number of manipulated sucklings must 
C.3. Other Protocol Review Considerations 133 

be included in the number of animals used. If suckling animals will be 

euthanized at or prior to weaning because they are the wrong genotype or 

sex for the experiment, then they may be included as animals held or 

euthanized but not subject to experimental manipulations. 

One option is for the IACUC to request estimated animal numbers as follows: 

Estimated number of weaned and adult animals 

* to be subject to experimental manipulations 

Estimated number of suckling animals to be * subject to experimental manipulations 

TOTAL

*Estimated numbers should be further subdivided based on invasiveness 

of procedures using institutional criteria: 

Estimated number of breeders held but not 

subject to experimental manipulations 

Estimated number of suckling animals to be 

euthanized at or prior to weaning, and not 

subject to experimental manipulation 

In summary, the IACUC’s role for oversight regarding breeding colonies 

includes ensuring that the need for a breeding colony has been established 

based on scientific or animal welfare concerns, that the procedures used in 

the breeding colony are evaluated and approved by the IACUC on a regular 

basis (e.g., as part of the semiannual program review), that there is a mechanism for tracking animals, and that the standards of care and animal wellbeing for the animals in the breeding colony are consistent with the Guide. 

References 

Beamer, W.G., Senior Staff Scientist, The Jackson Laboratory. Bar Harbor, ME. 

Personal communication. 

Festing, M.F.W. 1987. Animal production and breeding methods. In: The UFAW 

Handbook on the Care and Management of Laboratory Animals. 6th ed., pp. 18-34. 

T B Poole (ed). Churchill Livingstone Inc., New York. 

Fox, R.R. and B.A. Witham (eds). 1997. Handbook on Genetically Standardized JX 

mice. 5th edition, pp. 43-44, 120-125. The Jackson Laboratory. Bar Harbor, ME. 
134 C. Review of Proposals 

C.3.d. Field Studies 

Federal requirements and the Guide focus primarily on the care and use of 

laboratory animals in research facilities. The same guiding principles, however, apply to the use of vertebrate species in field studies. 

Application of the requirements and guidelines often pose unique challenges 

to the investigator and the IACUC because of the nature of field research. 

For example, field sites are often at a distance and may be remote, making 

it impractical for IACUC inspections. One solution is to require the investigator to provide photos, videotapes or other information that can help the 

committee evaluate the use of animals. For some projects the committee 

can find a consultant near the field site to perform an inspection and report 

to the IACUC. If the studies fall under the AWRs, at least two members of 

the IACUC must conduct the site inspections. Other difficulties relate to the 

nature of the research and the populations to be studied, which may be 

unfamiliar to the IACUC. 

Professional field biologists in organizations devoted to the study of fish, 

amphibians, reptiles, birds, and mammals have prepared guidelines for field 

work with these populations; these guidelines form a useful reference and 

can assist the investigator in planning, and the IACUC in reviewing, field 

research using vertebrate animals. The references at the end of this section 

cite such guidelines. Appendix E includes a list of professional societies 

and contact information. These organizations can assist by referring the 

IACUC to appropriate individuals and authorities. 

There is a comprehensive set of laws intended to protect wild animal populations. Appendix E describes these laws and the manner in which they are 

implemented and enforced. Virtually all activities involving birds, for example, 

require permitting under the Migratory Bird Treaty Act, the Endangered Species Act, the Bald and Golden Eagle Protection Act, or other permitting 

requirements. The investigator must be able to assure the IACUC that all 

necessary federal and state permits have been or will be obtained before 

research begins. 

The proposed study can be assessed by the IACUC in a manner similar to 

laboratory studies if the protocol prepared by the PI addresses the following relevant items: 

• species selection, 

• site selection, and 

• methodologies employed. 
C.3. Other Protocol Review Considerations 135 

Species Selection 

The investigator should provide information on the population to be studied 

and a rationale for choosing that particular population. The U.S. Fish and 

Wildlife Service (USFWS) issues many of the necessary permits. In issuing 

permits the USFWS assesses the risk to the animal population and the 

IACUC may rely on that assessment rather than attempt to determine the 

potential impact on the population. 

With regard to small or declining populations, many state wildlife or natural 

resource agencies also issue research permits. In the event that a state 

research permit is required and has been issued, the IACUC may assume 

that the state agency has assessed the risk to the population and found it 

to be acceptable. 

An IACUC that has additional questions about the selection of species or 

the impact on the population to be studied may require the investigator to 

provide additional information or the Committee may consult with biologists with relevant expertise. 

Site Selection 

The selection of the study site for the research should maximize the 

opportunity for data collection and minimize the disruption caused by the 

investigator. The selection process should also take into consideration other 

activities in the area, such as agricultural practices, tourism, and hunting, 

which may interfere with the research protocol. 

Permission to utilize the site may be necessary and the investigator must 

be able to assure the IACUC that necessary permits or permission have or 

will be obtained. Appendix E describes various site-specific permits required 

for field investigations. 

Methodologies Employed 

The potential short- and long-term effects of procedures on individual animals should be evaluated in all protocols. If animals are to be captured, the 

methods used and the numbers involved should be detailed in the protocol 

submitted to the IACUC. There should be a description of measures taken 

to prevent potential injuries and alleviate potential distress, and of the possible impact of capture on subsequent behavior and survival of the animals. 

If animals are to be monitored individually, the investigator must indicate 

whether they will be identified by natural markings or will be artificially 
136 C. Review of Proposals 

marked. If the animals are to be artificially marked, there must be a description of methods to be used and potential trauma (e.g., paint markings 

may increase visibility to predators). Capture and marking methods are 

often a matter of practicality and usually have been developed and evaluated over a period of time. There is a substantial body of literature regarding 

the effect of mark-and-recapture studies and other study techniques on 

wild animals. The IACUC or investigator may rely on consultation with 

experts in the relevant discipline for this information. In issuing permits the 

USFWS also assesses capture and marking activities, and the IACUC 

may rely on that assessment in considering the appropriateness of a 

particular technique. 

Field experimental procedures are commonly used to test hypotheses. In 

all instances, any potential pain or distress to an individual animal must be 

assessed and the investigator’s justification evaluated in the context of the 

potential value of the data to be obtained. 

Techniques for remotely recording behavioral or physiological data in the 

field are valuable and often minimally invasive. When possible, the least 

invasive procedures should be chosen (e.g., use of hormone assays of urine 

or feces rather than blood samples). When removal of individuals is necessary to take measurements or tissue samples, the IACUC should take into 

account the degree of invasiveness of the procedure and potential problems associated with return of the animal to the field. For example, animals 

should be released in a condition that enables them to avoid predators, 

seek shelter, and survive inclement weather. 

Individual animals may also be treated experimentally to alter their behavior 

or physiology by surgery or drugs. Any invasive surgery, such as organ removal or implanting transmitters, should be done using aseptic technique. 

The use and choice of anesthesia will be affected by field conditions 

because some agents are difficult to transport or use in field conditions. 

Anesthetics that do not clear from the system quickly may require holding 

the animal longer as they may compromise the animal’s ability to survive 

when released. The potential for human consumption of contaminated game 

species should also be considered. 

Procedures involving site manipulation should be adequately justified by 

the investigator. For example, investigators may remove or, in rare and 

well-justified cases, add a predator; however, state law may prohibit 

releases of non-native invasive species. If fences are erected to limit 

movement of individuals or populations, the impact on other species should 

be considered. 
C.3. Other Protocol Review Considerations 137 

Euthanasia of wildlife in the field can raise unique and challenging issues. 

The Report of the AVMA Panel on Euthanasia includes considerations and 

techniques for euthanasia of wildlife and should be used by the IACUC 

as a resource. 

Conclusion 

Many of these issues are difficult to address definitively, but their consideration will help the IACUC judge the potential impact and value of the 

study proposed, and can be expected to assist the investigator in obtaining 

maximum information from the study with minimum negative impact on the 

animals studied or their environment. The IACUC should ensure that the 

investigator complies with applicable regulations and policies and obtains 

any required permits; the IACUC may wish to obtain copies. Many of the 

issues arising from proposals to conduct field research on vertebrate animals will require the judgment of experienced professionals in the field and 

the IACUC should feel free to seek advice or consultation if necessary. 

References 

Acceptable field methods in mammalogy: Preliminary guidelines approved by the 

American Society of Mammalogists. 1987. J Mammalogy 68(4, Suppl.): 1-18. 

Bowman, P. 1989. Institutional animal care and use committee review of wildlife 

field research. Lab Animal 18 (3): 28-30. 

Burghardt, Z.M. and H.A. Herzog, Jr. 1980. Beyond conspecifics: Is Brer Rabbit our 

brother? Bioscience 30: 763-768. 

Guidelines for the Capture, Handling, and Care of Mammals. Undated. American 

Society of Mammologists. (http:www.mammalsociety.org/committees/ 

commanimalcareuse/98acucguidelines.PDF) 

Guidelines for the treatment of animals in behavioural research and teaching. 2000. 

Animal Behavior 59:253-257. 

Guidelines for the use of fish in field research. 1987. American Society of Ichthyologists and Herpetologists (SIH), American Fisheries Society (AFS), and the American 

Institute of Fisheries Research Biologists (AIFRB). Copeia (Suppl.) 1-12. Also: Fisheries 13(2):16-23. 

Guidelines for the Use of Live Amphibians and Reptiles in Field Research. 1987. 

American Society of Ichthyologists and Herpetologists (ASIH), The Herpetologists’ 

League (HL), and the Society for the Study of Amphibians and Reptiles (SSAR). 

J Herpetology 4 (Suppl.): 1-14. 

Guidelines to the use of wild birds in research. 2d Edition, 1999. The Ornithological 

Council. 
138 C. Review of Proposals 

(Available at www.nmnh.si.edu/BIRDNET or in hard copy for $8.00 per copy; send 

orders to Max Thompson, Assistant Treasurer, American Ornithologists’ Union, Dept. 

of Biology, 100 College Street, Winfield, KS 67158-8382). [Replaces in entirety the 

Report of committee on the use of wild birds in research. 1988. American Ornithologists’ Union, Auk 105(1, Suppl.): 1A-41A.] 

Orlans, F.B., Ed. 1988. Field research guidelines: Impact on animal care and use 

committee. Scientists Center for Animal Welfare. Bethesda, MD. 

Report of the AVMA Panel on Euthanasia, JAVMA, Vol. 218, No. 5, March 1, 2001. 

C.3.e. Hazardous Materials 

The IACUC must pay particular attention to proposals employing potentially hazardous materials, including: 

• radioactive substances, 

• infectious microorganisms, 

• biological toxins, 

• hazardous chemicals, and 

• recombinant DNA. 

These all have the potential of causing harm to animals in the facility and 

the personnel caring for and using them. 

Some hazardous materials are strictly controlled by federal, state and local 

regulations. Radiation Safety Committees (RSCs) and Institutional Biosafety 

Committees (IBCs) have been mandated by the federal government to 

ensure that certain radioactive materials and recombinant DNA materials 

are handled safely. The role of these committees may be extended to consider research involving human and animal pathogens. The IACUC should 

be generally familiar with the responsibilities of the various safety committees and organizations at their institution and the institution should ensure 

that the functions of the committees are coordinated. Animal research proposals should be consistent with the procedures required by the IBC. 

In addition to the various safety committees, institutions should have 

professional staff or resources available to handle chemical, biological and 

radiological agents. The National Research Council publication, Occupational Health and Safety in the Care and Use of Research Animals, is a 

valuable resource for IACUC members. This publication covers a wide 

variety of occupational health and safety issues, including information on 

working with hazardous materials in research animals. 
C.3. Other Protocol Review Considerations 139 

Radioactive Materials 

The U.S. Nuclear Regulatory Commission (USNRC) directly, or by its state 

designee, issues licenses permitting institutions to procure, use and dispose of specified radioactive materials. These licenses do not cover: 

• X-ray machines; 

• high voltage accelerators; 

• electron microscopes; and 

•	 radioactive materials from sources other than reactor by-products, 

although these are all sources of ionizing radiation. 

RSCs have oversight for the procurement, use and disposal of radioactive 

materials; therefore, their approval should be coordinated with IACUC 

review of any proposal that involves radioactivity. General information on 

potential health risks from exposure to ionizing radiation can be found in 

the USNRC Regulatory Guide. 

Biohazardous Materials 

Infectious diseases may be a factor in many animal studies due to 

natural infections as well as those specifically induced as part of research. 

Consensus biosafety guidelines have been established for the use of animals in research involving infectious agents (Biosafety in Microbiological 

and Biomedical Laboratories). These guidelines provide a concept for 

assessing risks and selecting appropriate safeguards. Four biosafety levels, which consist of combinations of practices, safety equipment and 

facilities, are described in this CDC/NIH document. 

Certain human pathogens as listed in the Select Agent List (Appendix A, 42 

CFR 72.6) must be registered and approved by the Centers for Disease 

Control (CDC) prior to transfer from one registered facility to another. Similar requirements are in place with the USDA for the transfer of foreign 

animal disease agents. 

The NIH publication, Guidelines for Research Involving Recombinant DNA 

Molecules, promulgated by the NIH Office of Biotechnology Activities, also 

includes four biosafety levels and represents a key reference for work 

involving recombinant microorganisms. Recombinant DNA experiments 

involving animals also require approval from the IBC. 
140 C. Review of Proposals 

Hazardous Chemicals 

In addition to animal care concerns, activities involving hazardous chemicals require procedures for: 

• chemical storage and disbursement, 

• dosage preparation and challenge procedures, and 

• waste management and disposal practices. 

It is also necessary to determine whether the chemicals will be present in 

feed, feces or urine. A rigorous review to ensure appropriate safety practices, containment equipment and facility safeguards is essential for animal 

experiments involving chemical inhalation. 

Proposals submitted to the IACUC must include sufficient documentation to assess the adequacy of precautions to control exposure of 

personnel to the hazardous agents involved in animal experiments. The 

identification by the IACUC of protocols involving hazardous chemicals 

(e.g., the use of known carcinogens to induce tumors in animal models, 

determinations of carcinogenicity, mutagenicity, or teratogenicity, or acute 

toxicity studies) is essential for institutional compliance with health and 

safety standards. The Occupational Safety and Health Administration (OSHA) 

laboratory standard “Occupational Exposure to Hazardous Chemicals in 

the Laboratory” is of particular importance. The IACUC should be familiar 

with the requirement in this standard for a chemical hygiene plan for controlling exposures to hazardous chemicals. Written standard operating 

procedures may be required describing appropriate safety precautions 

and specific “designated areas” where hazardous chemicals will be used 

or stored. 

One health and safety issue common to most IACUCs concerns the use 

of the inhalation agent ether for anesthesia and euthanasia. Ether forms 

explosive peroxide when stored in metal containers and must be used with 

special precautions because of its volatility and flammability. Ether must be 

used with special ventilation and kept away from flames or electrical ignition sources. Carcasses of animals euthanized with ether should be stored 

in explosion proof well-ventilated areas and not incinerated until the ether is 

volatilized. Other inhalation anesthetics, such as halothane, methoxyflurane 

and nitrous oxide, although not without some degree of toxicity in an occupational setting, are less hazardous when used with proper precautions 

and a waste gas scavenging system. Methoxyflurane is the most toxic of 

these inhalation agents to humans, and safe practices should be closely 

scrutinized by the IACUC. 
C.3. Other Protocol Review Considerations 141 

Another class of hazardous chemical routinely encountered in the laboratory environment is aldehydes. Specific OSHA guidelines are available for 

handling aldehydes and other chemicals. Material Safety Data Sheets, which 

provide useful information on specific hazardous chemicals, must be 

accessible on site for each hazardous agent present. 

Hazardous Waste 

Animal wastes contaminated with radioactive materials, recombinant 

organisms, infectious agents or other hazardous chemical agents must be 

carefully managed to avoid human exposure or damage to the environment. Special efforts should be made in experimental design to minimize 

the generation of wastes containing hazardous chemicals. Those containing radioactivity in addition to hazardous chemicals are particularly 

difficult to deal with. Wastes containing infectious agents should be 

decontaminated, preferably in a steam autoclave, before disposal. Incineration is the recommended treatment for contaminated feed and bedding. 

The professional health and safety staff, who have responsibility for hazardous waste management at the institution, should review institutional policies when animal care proposals involving hazardous materials are received. 

References 

Biosafety in Microbiological and Biomedical Laboratories, 4th Edition, May 1999. 

U.S. Department of Health and Human Services Publication (CDC) 93-8395. 

NIH Guidelines for Research Involving Recombinant DNA Molecules. NIH Office of 

Biotechnology Activities. 

Occupational Exposure to Hazardous Chemicals in Laboratories. January 31, 1990. 

Federal Register Vol. 55:3327-3335 29CFR1910.1450. 

U.S. Nuclear Regulatory Commission Regulatory Guide. 1996. Regulatory Guide 

8.29, Instruction concerning risks from occupational radiation exposure. 

Occupational Health and Safety in the Care and Use of Animals. 1997. National 

Research Council, National Academy Press, Washington, DC. 
142 C. Review of Proposals 

C.3.f. Instructional Use of Animals 

Any instructional use of live, vertebrate animals that is supported by the 

PHS is governed by the PHS Policy. The applicability of the AWRs depends 

upon the species used. Most institutions have chosen to require that all 

instructional use of animals, regardless of funding source or species, be 

reviewed by the IACUC. 

It may be appropriate for students, at both undergraduate and graduate 

levels, to participate in the conduct of experiments involving laboratory animals for the purpose of education. All instructional proposals should clearly 

identify the learning objectives and justify the particular value of animal use 

as part of the course, whether it is demonstration of a known phenomenon, 

acquisition of practical skills, or exposure to research. In all cases, consideration must be given to alternative approaches to attaining the desired 

educational objectives, in accordance with the U.S. Government Principles. 

Adequate supervision and training are especially important as the techniques learned by students may be carried into subsequent research 

careers. It is recommended that students receive instruction in the ethics 

of animal research and applicable rules and regulations prior to undertaking 

any experimentation. When students work in an investigator’s laboratory, 

the IACUC must ensure that the students receive appropriate supervision 

and training in animal care and use. The PHS Policy and AWRs have specific training requirements that apply to all animal users, including students. 

Student projects involving protocols different from those approved for the 

instructor’s laboratory must be reviewed and approved on their own merits 

by the IACUC. 

Experiments sometimes entail behavioral observation with no intervention, 

or minor painless interventions, such as choices of food or living accommodations. Such projects teach the rigors of conducting a research project 

and the variability inherent to biological or biobehavioral systems. These 

exercises generally involve little or no distress to the animals, but still 

require IACUC approval. 

Some procedures present additional concerns. Selected examples are 

listed below: 

•	 Behavioral studies that involve conditioning procedures in which 

animals are trained to perform tasks using mildly aversive stimuli, such 

as the noise of a buzzer, may be potentially stressful to the animals. 
C.3. Other Protocol Review Considerations 143 

For other behavioral studies using non-aversive stimuli, such as 

running mazes, it may be necessary to maintain animals at a reduced 

body weight to enable food treats to be used as an effective reward. 

Experiments involving food and water restriction for teaching purposes 

must be rigorously justified and carefully monitored. 

•	 Some behavioral studies produce potentially high levels of distress, 

including those using aversive stimuli, such as unavoidable noxious 

electric shock and surgical ablations or drug-induced lesions designed 

to affect the animal’s behavior or performance. The educational 

benefits of such procedures should be carefully reviewed and clearly 

justified, bearing in mind that studies involving unrelieved pain or 

distress are generally inappropriate when employed solely for 

instructional purposes (U.S. Government Principle IX). 

•	 Laboratory studies in physiology, neurophysiology, biology, and 

pharmacology often involve observations and experiments using animals. For all procedures, including those in which animals are 

euthanized to obtain tissues (e.g., in the teaching of anatomy or tissue 

harvest for in vitro procedures), the procedures and method of euthanasia, if any, must be reviewed by the IACUC. The number of animals 

used should always be the minimum necessary to accomplish the 

objectives of the proposed educational activity. 

Animal Use in Veterinary Teaching 

Many North American veterinary schools use live animals to teach anesthesia, animal handling, surgical procedures, recovery from anesthesia, 

post-operative management and postmortem examinations following 

terminal procedures. Animals designated for teaching may be kept long 

term and participate in many classes over the course of a year or more. 

All instructional use of animals in non-survival as well as survival instructional procedures should be reviewed by the IACUC. Repeated procedures 

on designated teaching animals should be limited and reviewed by the 

IACUC. Federal limitations on multiple survival surgeries must be observed. 

Cost savings alone is not an adequate reason for performing multiple survival surgical procedures. 

Some schools make alternatives available for those students who do not 

wish to participate in animal laboratories. Alternatives to the use of animals 

acquired specifically for instruction include the use of client-owned 

animals, or dogs and cats from animal control facilities that are made 
144 C. Review of Proposals 

available for surgical neutering. Plastic models and other model systems 

are increasingly being used to teach manual skills. 

Animals that develop unique and/or terminal conditions may be donated 

to a veterinary school for research and/or teaching purposes. The use of 

these animals needs full IACUC review. 

Animal Use in Agricultural Instruction 

Flocks and herds of agricultural animals are often maintained by agricultural schools to teach husbandry, production, and showmanship. 

Animals used for these practices are not covered by the PHS Policy (unless 

supported by PHS) or the AWRs. However, research procedures (e.g., 

in vitro fertilization), should have committee review. IACUCs charged with 

reviewing the use of animals in activities with agricultural applications will 

find A Guide for the Care and Use of Agricultural Animals in Agriculture 

Research and Teaching useful in conducting their evaluation. 

References 

Boschert, K. Oct. 1993. An overview of animal use alternatives in veterinary education. Lab Animal 22 (10) p. 36-42. Nature Publishing Company. New York, N.Y. 

Kahler, Susan C. March 15, 2000. Laboratories terminated, but lessons learned. 

JAVMA 216, No. 6, 

Smith, A., R. Fosse, D. Dewhurst, and K. Smith. 1997. Educational simulation 

models in the biomedical sciences. ILAR Journal 38 (2) p. 82-88. Institute of Laboratory Animal Resources, National Research Council. Washington, DC. 

Ungar, K. and D.C. Anderson. Summer 1994. An inventory of databases and 

other sources of information on alternatives to the use of animals in science 

education. Johns Hopkins Cent. Altern. Animal Test. The Center 11 (3) p. 12-18. 

Baltimore, MD. 

Use of animals in medical education. Aug. 14, 1991. JAMA 266 (6):836-837. The 

Association. Chicago, Ill. 

White, K.K., L.G. Wheaton, and S.A. Greene. Winter 1992. Curriculum change 

related to live animal use: A four-year surgical curriculum. J Vet Med Educ Vol. 19 

(1):6-10. The Association of American Veterinary Medical Colleges. Blacksburg, Va. 
C.3. Other Protocol Review Considerations 145 

C.3.g. Surgery 

Surgical procedures are a common component of animal research activities, and IACUCs are often called upon to assess the details of these 

procedures. Further, the IACUC is responsible for determining that personnel are qualified and trained in the procedures to be performed. 

Definitions 

Major surgery: Penetrates and exposes a body cavity or produces substantial impairment of physical or physiologic functions. 

Minor surgery: Does not expose a body cavity and causes little or no 

physical impairment. 

Survival surgery: The animal awakes from surgical anesthesia. 

Non-survival surgery: The animal is euthanized before recovery from 

anesthesia. 

Reviewing Protocols for Surgical Procedures 

Some of the aspects of a surgical procedure that the IACUC reviews are: 

•	 details of the procedure (e.g., the actual procedure itself, preand post-operative care, aseptic technique, sequence of multiple 

procedures); 

• appropriateness of the species for the procedure proposed; 

• qualifications of the personnel performing the surgical procedures; 

• species-specific and procedure-specific facility requirements; 

• patient monitoring practices in the surgical and post-surgical periods; and 

• personnel occupational health and safety issues. 

The veterinarian should always be one of the IACUC’s primary sources of 

information on surgery and post-operative issues. Other sources include 

the AWRs (9 CFR 2.31(d)(1) (ix) and (x)), the PHS Policy, the Guide, 

and other publications referenced at the end of this section. While the 

numerous references available provide background and a basis for reviewing surgical protocols, the IACUC relies on professional judgment to review 

the unique situations surrounding surgery in an experimental setting. Surgical procedures performed in a research setting have review requirements 

that may be different from those in a routine veterinary clinical setting. 
146 C. Review of Proposals 

Some of the surgical procedures proposed in research are experimental 

and may require ongoing review by the IACUC as the procedure is 

developed. Model development protocols, and close collaboration with 

the veterinarian and other experienced individuals, can be helpful in 

these circumstances. 

To perform a meaningful review, the IACUC must be provided with details 

of proposed surgical procedures. Such details give the IACUC the opportunity to assess the level of the investigator’s knowledge and need for 

additional training. 

Multiple Major Survival Surgery (MMSS) 

The Guide discourages multiple major survival surgery. The AWRs state 

that animals may not be used in these procedures unless: 

•	 there is a scientific justification (e.g., related components of the same 

study) provided by the principal investigator in writing; 

•	 the MMSS are required as a routine veterinary procedure or to protect 

the health and well-being of the animal, as determined by the attending veterinarian; or 

•	 under other special circumstances which have been approved by the 

Administrator of APHIS. 

The Guide suggests that reasons for MMSS may include procedures that 

are related components of a research project, procedures that will 

conserve scarce animal resources, or procedures conducted for clinical 

reasons. The Guide precludes cost savings as the sole justification for MMSS. 

Subsequent to approval of MMSS, the IACUC should ensure that there is 

sufficient ongoing oversight of the project. 

Special Considerations 

Some procedures are difficult or impossible to perform in some species 

of animals due to the nature of the animal (e.g., anatomical variation such 

as lack of a gall bladder, size of the animal, or size of a particular organ; 

sensitivity to antibiotics; or tolerance to a particular procedure). This can be 

an issue when a protocol involves an established procedure in a new 

animal model. Such protocols require particular attention and guidance 

from the IACUC. 
C.3. Other Protocol Review Considerations 147 

If a procedure may cause more than momentary or slight pain or distress, 

the AWRs prohibit the use of paralytics without concurrent anesthesia. 

Some procedures may require specialized facilities to ensure their success. 

For example, major survival surgery in non-rodents requires dedicated 

surgical facilities. Details of such physical requirements can be found in 

the Guide. The IACUC should assess the availability of necessary facilities 

during the protocol review process. 

Patient Monitoring 

The sophistication of patient monitoring required varies with the species 

and the procedure, but during protocol review, the IACUC should expect 

evidence of the following: 

• a pre-surgical assessment; 

•	 adequate monitoring of depth of anesthesia and animal homeostasis 

during the surgical procedure; 

• support such as fluid supplementation, external heat or ventilation; 

• monitoring and support during anesthetic recovery; and 

•	 post-surgical monitoring details, (e.g., what will be done and how 

often, who will be responsible, and the name and phone number of 

the individual to contact in the case of post-surgical complications). 

Recordkeeping 

Recordkeeping is an essential component of peri-operative care. For 

major surgical procedures on non-rodent mammals, an intra-operative 

anesthetic monitoring record should be kept and included with the surgeon’s 

report as part of the animal’s records. This record should be available to the 

personnel providing post-operative care. Post-operative records, at a minimum, should reflect that the animal was observed until it was extubated 

and had recovered the ability to stand. These should be supplemented 

by records evaluating the animal’s recovery, administration of analgesics 

and antibiotics, basic vital signs, monitoring for infection, wound care, and 

other medical observations. 
148 C. Review of Proposals 

Occupational Health and Safety 

Surgical situations can present certain occupational health and safety 

risks related to: 

• use of inhalation anesthetics, 

•	 use of certain species or a species under certain circumstances 

(e.g., pregnant sheep), or 

• use of certain devices (e.g., lasers). 

If the circumstances warrant it, the IACUC should consult with the applicable biosafety personnel. 

References 

Brown, M.J., P.T. Pearson, and F.N. Tomson. 1993. Guidelines for animal surgery 

in research and teaching. AJVR (54), 9:1544-1559. 

National Agriculture Library, 1994. Essentials for Animal Research: Principles of 

Aseptic Technique. 41-50. 

National Agriculture Library, 1994. Essentials for Animal Research: Perioperative 

Care. 51-66. 

Mangram, A.J., T. C. Horan, M.L. Pearson, L.C. Silver, and W.R. Jarvis, 1999. 

Guideline for Prevention of Surgical Site Infection, 1999. Inf Cont & Hosp Epi 

(20), 4:250-278. 

Academy of Surgical Research. 1989. Guidelines for training in surgical research in 

animals. J Invest Surg 2:263-268. 

C.3.h. Transgenic Animals 

A spontaneous mutation is a naturally occurring heritable alteration in the 

genetic code. Spontaneous mutations have been observed in virtually all 

species. An induced mutation is a man-made alteration in the genetic code. 

Induced mutant is a generic term including transgenic and targeted mutations that are created to study over-expression or under-expression of a 

specific gene. The altered gene must be predictably transmitted to offspring 

for a spontaneous or an induced mutation to be useful in research. To date, 

the majority of induced mutations have been made in laboratory mice of the 

genus Mus or laboratory rats of genus Rattus. Although mice are used as 

examples in the following discussion, the general considerations are applicable to induced mutants of any species. 
C.3. Other Protocol Review Considerations 149 

Transgenic refers to insertion of exogenous DNA (deoxyribonucleic acid) 

into cells. Typically, cDNA (complimentary deoxyribonucleic acid) made 

from specific mRNA (messenger ribonucleic acid) is inserted into cells 

using microinjection, electroporation or certain nonpathogenic viruses. 

(Electroporation is the brief application of an electric field to a cell to 

increase permeability of the cell membrane for purposes of introducing drugs 

or genes into the cell.) Each of these methods has been used to insert new 

DNA into the pronucleus of a fertilized mouse egg and to create transgenic 

mice. The manipulated fertilized eggs may or may not be cultured in vitro 

for one to three days before they are surgically implanted into the oviducts 

or uterus of pseudopregnant female mice. The inserted DNA incorporates 

in chromosomes of a percentage of embryos developing from the microinjected eggs. The DNA incorporates at different genetic locations and 

a different number of copies of the DNA may incorporate in different 

embryos. Thus, each embryo has the potential to become a unique 

transgenic mouse even though the same quantity and type of DNA was 

injected into genetically identical fertilized eggs. All manipulated, fertilized 

eggs do not become live born transgenic mice. Losses occur at every step 

from injection through gestation and delivery. 

Mice can carry transgenes, but unless the cDNA is incorporated into germ 

cells, the mouse is unable to transmit the transgene to its offspring. A 

mouse that passes the transgene to the descendants is called a ‘founder. 

Thus, many fertilized eggs have to be injected to obtain a few transgenic 

mice, and only a few of these transgenic mice will be ‘founders’ of this 

transgenic line. 

Targeted mutation refers to a process whereby a specific gene is made 

nonfunctional (‘knocked-out’) or less frequently made functional (‘knockedin’). Creation of a targeted mutation requires several steps in the laboratory. 

The specific gene is identified, cloned and manipulated to make it nonfunctional (‘knocked-out’). The manipulated gene is attached to another DNA 

sequence called a promoter and introduced into embryonic stem (ES) cells 

by electrical or chemical methods. These ES cells are cultured in special 

media that permits identification of ES cells incorporating the manipulated 

gene. ES cells incorporating the manipulated gene are injected into an early 

embryo (blastocyst). The ES cell injected blastocysts are surgically implanted 

into the uterus of pseudopregnant female mice. Some injected blastocysts 

develop into viable embryos and gene deficient ‘knock-out’ mice are born. 
150 C. Review of Proposals 

Many blastocysts have to be injected to obtain a few new ‘knock-out’ mice, 

and only a few of the new ‘knock-out’ mice will incorporate the ‘knockedout’ gene in their germ cells and become ‘founders’. 

If a project uses a spontaneous or induced mutant model and the mutant 

animal can be purchased from a resource or commercial colony, review of 

this project is similar to review of any other project. If a project uses an 

induced mutant model and only breeders are available from the source, 

review of this project is similar to review of any other breeding colony. In 

either case, the IACUC should determine if the mutant gene will result in a 

severely debilitating phenotype, if anything can or will be done to ameliorate such phenotype, and what endpoints will be used to determine when a 

mutant animal will be euthanized. Simple husbandry measures can modify 

the severity of some mutant phenotypes. For example, ground feed or moist 

feed can extend life and improve growth of mutants with missing or malformed teeth. Food and water on the bottom of the cage may be easier for 

mutant rodents with neuromuscular abnormalities to access than food in a 

traditional feeder built into a cage lid. Extra bedding helps dwarf mice reach 

food and water. Extra bedding helps absorb urine produced by diabetic 

mice or other mice that excrete large quantities of urine. A normal cage 

mate, a solid bottom cage with extra bedding, or a slight increase in room 

temperature can benefit mutant rodents that have problems maintaining 

body temperature (Beamer, 1986). 

When an investigator prepares a proposal that includes development 

of a new mutant model, information about clinical abnormalities associated 

with the phenotype, special husbandry requirements, etc. will not be available. However, the investigator should include general criteria for euthanasia if a severe debilitating phenotype develops, and provide the IACUC with 

this information when the new mutant has been developed or at the next 

annual review. 

The standard of ‘normal’ for a mutant animal may or may not be the same 

as for a non-mutant animal. If the mutant phenotype does not impact 

clinical well-being of the animal, the same standard of ‘normal’ can be used 

for mutant and non-mutant animal. In the mouse, brown (gene symbol 

Tyr<b>) and short ear (Bmp5<se>) are examples of spontaneous mutations 
C.3. Other Protocol Review Considerations 151 

that produce no observable, clinical impact on the well-being of the mouse. 

If the mutant phenotype has minimal impact on the well-being of the 

animal, the standard of ‘normal’ can be similar for mutant and non-mutant 

animal. Hypogondal (Gnhr<hpg>) and ‘little’ (Ghrhr<lit>) are examples 

of spontaneous mutations with minimal impact on well being of the mouse. 

Homozygous hypogondal mice are normal in all ways except for small, nonfunctional gonads. Homozygous ‘little’ mice are smaller than non-mutant 

littermates. Growth hormone transgenic mice tend to have larger body size 

than normal, but are otherwise clinically normal with the exception of reduced fertility. 

In the case of mutants where phenotype involves clinical abnormalities, the 

standard for ’normal’ may have to be modified to encompass the expected 

phenotype. For example, 4 to 5 week old homozygous dystrophic mice 

(Lama<dy-2J>) have difficulty abducting hindlegs and have an abnormal 

gait. As these mice age, muscular weakness progresses in hindlegs and 

eventually extends to involve all skeletal muscles. The standard for ‘normal’ 

for homozygous dystrophic mice must include difficulty abducting hindlegs 

and an abnormal gait. Adenopolyposis coli ‘knock-out’ mutant mice 

(Apc<Min>) are clinically normal until the intestinal polyps develop, after 

which time the mice become anemic and lose weight. Experimental endpoints for these latter and similar mutant models should focus on (1) ability 

of the mutant to access feed and water, (2) response of the mutant to stimuli, 

and (3) general condition of the mutant (i.e., is the mutant excessively thin, 

showing progressive weight loss or hunched posture?). 

Many institutions have a centralized induced mutant facility that receives 

the genetic material from investigators and performs the manipulations to 

develop ‘founder’ transgenic or ‘knock-out’ mice. The ‘founder’ mice are 

returned to the investigator who undertakes breeding to expand the line. 

Review of the centralized induced mutant facility should focus on personnel qualifications, animal related practices such as aseptic surgery, and 

average number of mice required to produce ‘founders’ for a single DNA 

construct, recognizing, however, that the number of mice required is a very 

rough estimate because of differences in responses of different strains or 

stocks of mice, variations in success rate for different DNA constructs, and 

subtle or less subtle uncontrollable environmental changes. 
152 C. Review of Proposals 

In many non-mutant model experiments, an investigator can accurately 

estimate the exact number of animals required to test a hypothesis. However, when creating an induced mutant, there are major variables that make 

it difficult to accurately estimate the number of required animals, including: 

•	 differences in percent successful microinjections of pronuclei or 

successful incorporations of altered gene into ES cells, 

•	 differences in percent successful surgical transfers of fertilized eggs 

or blastocysts, and 

•	 differences in percent successful incorporation of exogenous DNA or 

altered gene into germ cells of induced mutant mice. 

Different strains of mice vary in their responses to each of these manipulations. Different genes (‘constructs’) vary in the ease with which they insert 

as a transgene or are ‘knocked-out’. These variables remain even when the 

same skilled people perform each manipulation. 

References 

Beamer, W. “Use of Mutant Mice in Biological Research.” 12/8/89, SCAW Conference: Guidelines for the Well-being of Rodents in Research, Proceedings edited by 

H. Guttmann. 

Gordon, J.W. 1990. Transgenic animals. Lab Animal 19(3):27-30. 

Hogan, B., F. Constantini and L. Lacey. 1986. Manipulating the Mouse Embryo: A 

Laboratory Manual. Cold Springs Harbor Laboratory Press. Cold Springs Harbor, NY. 

Kovacs, M.S., L. Lowe and M.R. Kuehn. 1993. Use of superovulated mice as 

embryo donors for ES cell injected chimeras. Lab Anim Sci 43:91-93. 

Mobraaten, L.E. 1981. The Jackson Laboratory Genetics Stocks Resource Repository. In Frozen Storage of Laboratory Animals. Zeilmaker, GD (ed). Gustav, Fisher, 

Verlag. New York. pp. 165-1177. 

Wilson E.D., and M.X. Zarrow. 1962. Comparison of superovulation in the immature 

mouse and rat. J Reprod Fert 3:148-158. 

Zarrow, M.Z. and E.D. Wilson. 1961. The influence of age on superovulation in the 

immature rat and mouse. Endocrinology 69:851-855. 
C.4. Monitoring of Approved Protocols 

After the IACUC has approved a protocol, it has a responsibility to ensure 

that procedures are carried out in the laboratory or classroom as described 

in the protocol. This section will briefly review ways that the IACUC can 

monitor the conduct of approved protocols. 

Acquisition and Tracking 

Animals should be obtained only from licensed dealers or other legal sources, 

and it is incumbent upon an institution to establish mechanisms to monitor 

and document the number of animals acquired and used in approved 

activities. This is best accomplished if animal purchases may be made 

only through the institution’s animal resource facility or other appropriately 

designated office. Once animals have been acquired, they should be 

included in a tracking system. Many institutions have automated systems 

that will alert an appropriate individual when an investigator has reached a 

preset percentage (e.g., 80 to 90%) of the number of animals approved for 

a specific project, and can prevent ordering animals in excess of the number approved. Institutions with small programs using limited numbers of 

animals may choose to maintain a manual log of IACUC approved activities 

and numbers of animals acquired. 

Tracking animal use becomes more complicated when investigators maintain breeding colonies. Keeping track of animal usage may be accomplished 

by requiring that investigators with breeding colonies maintain accurate 

records. Investigators can be required to report to the designated office, at 

regular intervals, the number of animals born, weaned, or used in studies. 

This report can be tallied against the numbers in the approved protocol. 

Compliance Specialist 

Some IACUCs have a full or part-time compliance specialist who monitors 

procedures in vivaria, laboratories, and classrooms, and reports his or 

her observations to the IACUC. This individual should have laboratory 

animal training and experience, and be authorized to conduct announced 

or unannounced laboratory inspections on behalf of the IACUC. In addition 

to this role, the compliance specialist may periodically survey individual 

153 
154 C. Review of Proposals 

laboratories to ensure that actual procedures used are consistent with 

protocols. The survey may include meeting with investigators and staff to 

review concerns, answer questions, and identify procedures that may deviate from those originally approved by the IACUC. In cases of deviation, the 

specialist should notify the IACUC. 

Eyes and Ears 

Research, veterinary, and husbandry staff should be aware of approved 

procedures for use on animals when they have responsibility for those 

animals. This may be accomplished by informing these individuals in 

staff meetings or by making standard operating procedures and animal use 

protocols readily accessible in the laboratory or vivarium. These practices 

help to ensure that procedures being used are, in fact, those that were 

approved by the IACUC. Maintaining an open environment in which staff 

can discuss apparent departures from approved procedures with the 

investigator often facilitates compliance and the rapid correction of 

deviations. Staff must also be free to report perceived deviations to the 

IACUC, which must then consider such concerns (see Section D). 

Semiannual Inspection 

During the semiannual facility inspections, IACUC members should note 

the use of animals and may verify that the observed procedures are consistent with the protocol on file. 

Retrospective Reporting of Adverse Events 

The USDA requires that the number of covered animals used in each pain/ 

distress category be reported annually, but there are currently no explicit 

federal requirements for reporting of unexpected or unintentional changes 

in pain category, morbidity, or mortality after the event. The USDA does 

expect any significant deviations from the expected pain/distress category 

to be reported correctly. Institutions may choose to require an accounting 

of unexpected, unintentional, or adverse events as a means of identifying 

deficiencies in procedures, faults in study design, or need for additional 

personnel training. 
C.4. Monitoring of Approved Protocols 155 

Review of Publications 

In academic institutions and many companies, much research is eventually 

published. Some IACUCs choose to review some published descriptions of 

animal use to verify that work was done according to the approved protocol. 

Conclusion 

Although no IACUC has the staff or time to observe all animal use in an institution, the IACUC can help establish a climate of compliance. To ensure that 

animal use conforms to local policy and federal regulations, it is prudent for 

the IACUC to confirm that animals are used according to protocol. 
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D. Evaluation of Animal


Care and Use Concerns


157

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Evaluation of Animal Care and Use Concerns 

To help ensure that laboratory animals receive humane care and use or 

treatment in accordance with the highest ethical standards, laws, regula	

tions and policies governing animal research, the IACUC must review and, 

if warranted, address any animal-related concerns raised by the public or 

institutional employees. Procedures must be established to ensure that 

concerns are communicated to the IACUC. The Committee must review 

each concern in a timely and systematic manner and, when necessary, take 

prompt, appropriate corrective actions. 

PHS Policy, Animal Welfare Act, and USDA AWR requirements 

The PHS Policy requires the IACUC to “review concerns involving the care 

and use of animals at the institution”, and the Guide states that the IACUC 

is responsible for “establishment of a mechanism for receipt and review 

of concerns involving the care and use of animals.” The Animal Welfare 

Act (AWA) (7 U.S.C. 2142; Section 13) requires training of personnel who 

are involved in animal care or treatment, including “methods whereby defi	

ciencies in animal care and treatment should be reported.” The AWRs 

(9 CFR Part 2, Subpart C, 2.32 (c)(4)) require each research facility to 

provide the methods whereby any employee of the facility can report defi	

ciencies in animal care and treatment. In addition, the AWRs, Section 

2.31(c)(4)) require the IACUC to “review and, if warranted, investigate con	

cerns involving the care and use of animals at the facility resulting from 

public complaints received and from reports of noncompliance received 

from laboratory or research facility personnel or employees.” 

In addition, the AWRs (9 CFR Part 2, Subpart C, Section 2.32(c)(4)) state 

that “no facility employee, Committee member, or laboratory personnel shall 

be discriminated against or be subject to any reprisal for reporting viola	

tions of any regulation or standards under the [Animal Welfare] Act.” 

Compliance 

To ensure compliance with federal law, regulations, and policies, it is strongly 

recommended that each IACUC develop and implement policies and pro	

cedures to ensure that all animal care and use concerns are brought to its 

attention for consideration. Some of the elements that should be included 

159 
160 D. Evaluation of Animal Care and Use Concerns 

in these procedures are described below (see IACUC Responses to 

Complaints). Institutional policy should contain provisions to protect the 

confidentiality of those who report concerns as well as anyone against 

whom allegations are directed, while allegations are under investigation. 

The policy should also address mechanisms for protecting complainants 

from reprisals. 

Origins of Concerns or Complaints 

Some common sources include: 

•
 animal care and use personnel – these individuals should receive 

instruction in institutional training programs to report perceived 

deficiencies in animal care or use to the IACUC. 

•
 other personnel – these persons (e.g., secretarial, maintenance, secu	

rity staff) are likely to direct concerns to a member of the research, 

animal care or veterinary staff, but they should be instructed to report 

concerns to the IACUC. 

•
 employee “hotlines” or ombudsmen – personnel responsible for these 

functions should be sensitive to animal-related concerns and notify 

the IACUC Chair of any that may arise. 

•
 the public – they are most likely to direct complaints to senior 

institutional representatives who should promptly forward them to 

the IACUC Chair. 

•
 anonymous – these complainants may or may not be institutional 

employees. 

•	 the media – stories appearing in newspapers, and on television or 

radio, etc. may contain or evoke concerns about animal care and use; 

such reports should be evaluated by the IACUC, and, when appropri	

ate, the institution should proactively address them. 

Methods for Reporting Concerns 

To facilitate communication, the names and phone numbers of contact 

persons, including IACUC members, the veterinarian, security office, and 

ombudsman/hotline, if one exists, should be posted in or near the entrance 

to animal facilities or listed on a Web site that is readily available to institu	

tional employees. This information should also be provided during training 

sessions as described above. 
Evaluation of Animal Care and Use Concerns 161 

Although written concerns are more convenient to deal with, complainants 

may not be willing to submit them in this manner. In such cases, the 

individuals who receive concerns should document them fully to ensure 

that the issues are clear and to prevent misunderstandings. Requests for 

anonymity should be honored to the extent possible. 

IACUC Responses to Complaints 

While specific methods for evaluating concerns about animal care and 

use may vary from institution to institution, all methods should contain 

these elements: 

• There should be a procedure for verifying stated concerns. 

•
 Verified concerns should be related to the AWRs, the PHS Policy or 

institutional policies. 

•
 There should be guidelines for effecting appropriate corrective 

measures, when necessary. 

One of the roles of the IACUC is to review all concerns about the animal 

care and use program, regardless of origin, and investigate them if warranted. The IACUC Chair is normally responsible for ensuring that concerns 

are addressed, but may delegate investigation to a subcommittee. If the 

Chair has, or is perceived to have, a conflict of interest, the Institutional 

Official (IO) should delegate the responsibility for assuring that the concern 

is addressed to another non-conflicted member of the IACUC. 

Concerns may include situations or activities ranging from those in which 

animals are reported to be in immediate, actual or perceived jeopardy to 

those in which violations of the AWRs or institutional Animal Welfare Assur

ances are alleged to be occurring but animals are not in apparent danger. 

They may focus on allegations of past policy and procedure violations. 

The course of action taken by the IACUC should be driven by the potential 

significance of the alleged situation. For example, conditions that report	

edly jeopardize the health or well-being of animals should be evaluated 

immediately. To cope promptly with such situations, some institutions have 

policies whereby a veterinarian or other designated person is authorized 

to halt procedures which they believe do not comply with institutional poli	

cies until the IACUC can be convened and consider the matter formally. 

Similarly, situations that may involve potential criminal activity or human 

safety should be reported promptly to the institution’s law enforcement or 
162 D. Evaluation of Animal Care and Use Concerns 

occupational health and safety officials. Allegations of other ongoing 

policy or procedural matters may not require such same-day attention, but 

should not be deferred merely as a matter of convenience. Emergency meet	

ings may be necessary in these cases to ensure prompt consideration 

of concerns. 

IACUC procedures for handling complaints may involve reviewing them 

with the veterinarian. Depending on the nature of the concern, the IO, 

legal counsel, and the person who submitted or fielded the complaint may 

also be invited to participate. Based on the results of its initial evaluation, a 

course of action—which may include further investigation—will then be 

determined and implemented. The IACUC should acknowledge receipt of 

concerns when the complainant is known. Details concerning the com	

plaint, complainant, persons against whom allegations may have been 

directed, and the investigations in progress are usually considered confi	

dential. However, when the Committee releases the report of its findings 

(including corrective actions, if applicable), those reports may become 

accessible to the public under state “sunshine” laws, and if provided to 

Federal regulatory agencies, under the Freedom of Information Act. 

The AWRs and the PHS Policy authorize the IACUC to suspend an activity 

after review of the matter at a convened meeting of a quorum of the IACUC 

and with the suspension vote of a majority of the quorum present. Suspen	

sions must also be reviewed by the IO in consultation with the Committee; 

appropriate corrective action taken by the IO is reported to OLAW. 

Most institutions have developed self-regulatory policies and procedures 

that supplement formal suspensions by the IACUC and are intended to 

ensure adherence to institutional and regulatory requirements. Depending 

on the severity of noncompliance or deviation from accepted practices, 

these range from counseling and mandatory remedial training to specific 

monitoring of animal use, temporary revocation of animal use privileges, or 

termination of employment. 

Model 

One model for considering concerns about animal care and use is outlined 

on the following pages. This example may not apply to all institutions, and 

may be adapted, as needed, in designing guidelines that are appropriate 

for individual institutions. 
Evaluation of Animal Care and Use Concerns 163 

Suggessted IACUC Procedures for the Investigation of 

Animal Care and Use Concerns* 

Initial Evaluation and Actions 

Upon receipt of a concern the IACUC Chair should convene a meeting of 

the IACUC. After initial review of the complaint the IACUC should determine whether it requires further investigation and immediate action, further 

investigation but no immediate action, or no action. Once this decision has 

been made, the IACUC should determine which individuals or other institu	

tional or noninstitutional offices may require notification at this time. 

If immediate action appears warranted because animal or human welfare 

may be compromised, the IACUC should notify the IO and proceed accord	

ingly. Veterinary medical intervention, suspension of a research activity, and/ 

or notification of appropriate safety, occupational health, or other officials, 

are examples of actions that may be taken immediately to protect animal or 

human welfare. In accordance with the AWRs (9 CFR Part 2, Subpart C, 

Section 2.31[d][7]), if an activity is suspended, the IO shall report that action 

to APHIS and any federal agency funding that activity. If the activity is supported in any way by the PHS, the IACUC, through the IO, must promptly 

notify OLAW (PHS Policy, IV.F.3.) (OPRR Reports 94-02, 1/12/94). 

Investigation 

Should the IACUC determine that further investigation is required, the Chair, 

or another individual or subcommittee appointed by the Chair, should conduct the investigation and report back to the IACUC. It is important to avoid 

actual or perceived conflicts of interest in this process. 

The IACUC should charge the designated person or group with its require	

ments for information gathering and impose a completion date. The 

assigned completion date will depend on the IACUC’s determination of 

whether immediate remedial action may be required. 

*DISCLAIMER 

Neither the AWRs nor the PHS Policy provide specific guidance regarding the consideration of 

concerns or the institutional conduct of investigations. Owing to the considerable diversity of 

concerns that may arise and the contexts in which they may be voiced, no one set of procedures will be suitable for investigating all potential situations that involve violations of or deviations from animal care and use practices required by the PHS Policy, AWRs, the Guide and 

other federal statutes and regulations regarding animals. Consequently, the following suggestions are broad, intended for general use, and not intended for application in all situations. 
164 D. Evaluation of Animal Care and Use Concerns 

The nature of the information required will vary depending on the circum	

stances, but often involves: 

•
 interviewing complainants (if known), any persons against whom 

allegations were directed, and pertinent program officials; 

• observing the animals and their environment; and 

•
 reviewing any pertinent records, (e.g., animal health records, protocol, 

and other documents). 

The designated investigator(s) should provide a report to the IACUC which 

summarizes: 

• the concern(s), 

• the results of interviews, 

• the condition of animals and their environment, and 

• the results of records and other document reviews. 

The report should also contain: 

•
 any supporting documentation such as correspondence, reports, and 

animal records; 

•
 conclusions regarding the substance of the concerns vis-à-vis re

quirements of the AWRs, the PHS Policy, the Guide, and institutional 

policies and procedures; and 

• recommended actions, if appropriate. 

Outcomes and Final Actions 

Upon receipt and evaluation of the report, the IACUC may request further 

information or find that: 

• there was no evidence to support the concern or complaint, 

•
 the concern or complaint was not sustained, but a) related aspects 

of the animal care and use program require further review or b) other 

institutional programs may require review, or 

• the concern or complaint was valid. 
Evaluation of Animal Care and Use Concerns 165 

Subsequent actions of the IACUC may include: 

•
 implementing measures to prevent recurrence (such measures often 

include changes in administrative, management or IACUC policies and 

procedures, and may include sanctions*); 

• notifying the IO and the AV of its actions; 

• notifying funding or regulatory agencies, as required; and 

•
 notifying the complainant, any persons against whom allegations were 

directed, and pertinent program officials (appropriate supervisory and 

management staff, the public affairs office, institutional attorneys, etc.). 

*Note on Sanctions: Aside from empowering the IACUC to suspend a pre	

viously approved activity, the AWRs and the PHS Policy are silent regarding 

IACUC- or institutionally imposed sanctions. 

Some institutions, as part of their programs, have developed policies and 

procedures that authorize the IACUC to impose sanctions on behalf of 

the institution. In other institutions, IACUCs recommend actions to the 

IO for implementation, and in still others, there exists a combination of 

these approaches. Some of the institutional sanctions that have been 

devised include: 

• counseling; 

• issuing letters of reprimand; 

• mandating specific training aimed at preventing future incidents; 

•
 monitoring by the IACUC or IACUC-appointed individuals of research, 

testing, or training involving animals; 

•
 temporary revocation of privileges to provide animal care or to 

conduct research, testing, or training that involves animals, pending 

compliance with specific, IACUC-mandated conditions; 

•
 permanent revocation of privileges to provide animal care or to 

conduct research, testing, or training that involves animals; and 

•
 recommending to the IO that institutional (e.g., reassignment, termi	

nation of employment) sanctions be imposed. 
166 D. Evaluation of Animal Care and Use Concerns 

Concerns Unrelated to Animal Care and Use 

The IACUC may determine, either in its initial evaluation of a concern or as 

a result of investigation, that violations of non-animal-related institutional 

policies and procedures, local, state or federal statutes, regulations, or laws 

may have occurred (e.g., scientific misconduct, misuse of monies, fraud, 

theft, etc). In such cases, those findings should be reported to appropriate 

institutional officials or committees for their consideration. 
E. Recordkeeping and 

Communications 

167­
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E.1. Recordkeeping and Reporting 

Introduction 

The PHS Policy and AWRs include recordkeeping and reporting requirements. The responsibility for these functions should be clearly delegated. 

Usually the IACUC office is assigned this task. The individuals responsible 

should understand federal animal use requirements and the institution’s 

program, and should also be aware of the Freedom of Information Act (FOIA) 

and any state open records laws. Many of the reports written may be 

accessible under such laws, and care should be taken to use language that 

is clear and precise to ensure accurate interpretation. 

Recordkeeping 

Minutes 

The PHS Policy and the AWRs require that the institution maintain “minutes 

of IACUC meetings, including records of attendance, activities of the 

Committee, and Committee deliberations” (PHS Policy IV. E; 9 CFR Part 2 

Subpart C 2.35 (a)(1)). The IACUC has some latitude in the degree of detail 

in these minutes. 

Records of attendance: Although members may arrive late or leave during a 

meeting, generally a member is marked as either present or absent. An 

exception would be when the IACUC member leaves the meeting room 

during discussion of a protocol on which that member is a participant. If the 

temporary absence of a member drops the number of members present 

below the quorum, this should be noted in the minutes. Certain official IACUC 

actions require a quorum (see Section A.2. Quorum Requirements). 

Activities of the Committee include corrections or approval of previous 

minutes; presentation of program, policy, facility and compliance reports; 

and decisions on policies, protocols, and amendments. 

Deliberations refers to the discussion and reasons leading to particular 

IACUC decisions. Although some IACUCs maintain a verbatim record 

(e.g., audio or videotapes), minutes should include as a minimum a summary of the key points discussed prior to a committee decision. 

169 
170 E. Recordkeeping and Communications 

Protocols 

The PHS Policy and the AWRs require that animal applications and proposed significant changes be retained for the duration of the animal activity 

and for an additional three years after the end of the activity. Proposals 

submitted to the IACUC must be kept for three years even if approval was 

not granted or animals were not used. The records must show whether or 

not IACUC approval was given. 

Other records 

Both the PHS Policy and the AWRs require that semiannual IACUC reports 

and recommendations be retained by the institution. PHS also requires that 

the OLAW Assurance and reports of accrediting agencies (e.g., AAALAC) 

be kept on file. USDA requires additional records on dogs and cats 

acquired, transported, sold, or euthanized by the research facility. Animal 

health records are not usually maintained by the IACUC but are kept in the 

animal facility. All these records must be kept for at least three years; and 

must be accessible to PHS, APHIS, and funding agencies for inspection or 

copying (see Table A ). 

Reporting Requirements 

PHS Assurance 

In order to qualify for support from the PHS for activities involving animals, 

institutions must provide an Assurance of Compliance with the PHS Policy. 

The Assurance is a written agreement that fully describes the institution’s 

program and commits the organization to comply with the PHS Policy, and 

in which the institution outlines in detail its policies and procedures. A 

sample Assurance is available at the OLAW Web site. Institutions that 

are not accredited by AAALAC must submit, with their Assurance, the 

most recent IACUC semiannual program evaluation. The completed 

Assurance, signed by the IO with appropriate authority, is submitted to and 

evaluated by OLAW. Upon final approval by OLAW an Assurance number 

(in the format A####-01 where # is a digit) is assigned to the institution. 

Assurances are approved for a period of up to five years, after which time 

the institution must submit a new Assurance. A list of institutions with 

approved Assurances is available on the OLAW Web site. 
E.1. Recordkeeping and Reporting 171 

It is important that the approved Assurance document is distributed appropriately within the institution and that members of the IACUC are familiar 

with this document, as compliance with the Assurance is required to be 

eligible for PHS funding. 

USDA Registration 

Institutions that use species of animals covered by the AWRs for research, 

testing, experiments, or teaching on its premises as specified in the AWA 

are required to be registered with the Animal Care division of the Animal 

and Plant Health Inspection Service (APHIS), using APHIS form 7011. The 

form is submitted to APHIS via the Regional Director of Animal Care (AC) for 

the state in which the facility has its principal place of business. At academic institutions, the submission is usually made by the institution, not the 

individual departments or schools, and signed by the IO. An approved USDA 

registration is given a number in the format ##-X-####, where X is a letter 

(R for research institution) and # is usually a digit. The registration may 

be renewed every three years. The institution is required to notify the AC 

Regional Director within ten (10) days of any change in the name, address, 

ownership or operations affecting its status as a research facility. The 

Regional Director may place a facility that has not housed animals for two 

years in inactive status. The registration can be cancelled by written 

request if a facility no longer uses, or intends to use, animals (see Table B). 

Semiannual Facility Inspections and Program Evaluations 

The PHS Policy and the AWRs require that the IACUC evaluate the 

institution’s animal program at least once every six months, including an 

inspection of facilities, and submit a report to the IO. The PHS Policy allows 

the IACUC discretion in how it evaluates its facilities and program. The 

report format is not mandated, but OLAW offers models for both facility 

inspections and program reviews on its Web site. 

The report must contain a description of the nature and extent of the 

institution’s compliance with the PHS Policy and Guide; any departures must 

be identified and modifications proposed, with a plan and timetable for 

correction. Any minority views of IACUC members must be included. 
172 E. Recordkeeping and Communications 

Minor and significant deficiencies must be distinguished. A significant

deficiency is defined as one that “is or may be a threat to the health or 

safety of animals.” Program or facility deficiencies, including accidents or 

natural disasters, which cause injury, death, or severe distress in animals, 

are, by definition, ‘significant.’ Examples of minor deficiencies include 

chipped paint and burnt-out light bulbs. The report must also identify any 

facilities that are AAALAC accredited. 

The IACUC may utilize AAALAC program status evaluations, accreditation, 

or pre-assessment preparation activities as a semiannual evaluation. To be 

used as the semiannual report, the report must include all the information 

required in Section IV.B.3 of the PHS Policy (see Table C), and be approved 

by vote of the IACUC. 

Semiannual reports are only submitted to OLAW under two circumstances: 

1) If an institution is not accredited by AAALAC, a copy of the most 

recent semiannual report must be submitted to OLAW with a new 

or renewal Assurance. 

2) Upon request by OLAW or other PHS representatives. 

USDA requirements are essentially the same as those for PHS with three 

exceptions: 

1) The AWRs include additional reporting requirements if the schedule 

and plan for correcting a deficiency is not followed. Failure to correct 

a significant deficiency in accordance with the specified schedule 

and plan must be reported in writing within fifteen business days by 

the IACUC, through the IO, to APHIS and any federal agency funding 

the activity. 

2) USDA requires that reports be reviewed and signed by a majority of 

IACUC members. 

3) USDA does not require the identification of facilities accredited by 

AAALAC. 

As with the PHS semiannual review, AAALAC processes may also fulfill 

the requirements for the USDA semiannual report provided Section 2.31 (c) 

requirements are met, as listed in Table C. 
E.1. Recordkeeping and Reporting 173 

Annual Report 

The IACUC at an institution with an approved PHS Assurance must submit 

an annual report to OLAW through the IO. This report details changes in the 

animal care and use program, IACUC membership, and AAALAC accreditation status. Minority reports from IACUC members must be included. It 

also includes the dates of semiannual review and reports submitted to the 

IO. The PHS and AAALAC annual reporting dates may be synchronized 

with the USDA reports. 

A sample annual report format is provided on OLAW’s Web site and may 

be utilized, but is not required. 

On or before December 1, each facility registered with the USDA must submit an annual report to the APHIS, AC Regional Director, for the state in 

which the facility is registered. Form 7023 is usually prepared by the IACUC 

and signed by the CEO or IO. It lists the number of each covered species 

used, by pain categories. The report includes assurances that animal care 

and use are at professionally accepted standards, that alternatives to painful procedures have been considered (see Section C.2.a. Alternatives) and 

that AWRs are followed. 

When an IACUC-approved deviation from USDA standards and regulations 

is required for scientific or other reasons, the report must address the reasons for the deviation, and the number and species of animals affected. 

Suspension and Noncompliance 

At an institution with an approved PHS Assurance, the IACUC must report 

promptly, through the IO, the circumstances and actions taken in the following instances: 

• any serious or continuing non-compliance with the PHS Policy, 

• any serious deviation from the provisions of the Guide, and 

• any suspension of any activity by the IACUC. 

It is recommended that the institution contact OLAW immediately following 

the event, and send a formal report, describing the circumstances and 

any actions taken, to OLAW after IACUC and IO review. Similarly, accredited institutions must report promptly to AAALAC serious issues relating 

to the animal care and use program, such as investigations by the USDA 

or OLAW, or other serious incidents or concerns that negatively affect animal well-being. 
174 E. Recordkeeping and Communications 

If the IACUC suspends any activities involving USDA-covered animals, 

the IO files a report with the AC Regional Director, in consultation with the 

IACUC. After reviewing the reasons for the suspension and taking appropriate corrective actions, the IO is responsible for submitting a full explanation 

to APHIS and any federal agency funding the activity (see Tables E and 

A.2.B.). 

E.1. Table A. Federal Requirements: Recordkeeping 

Records PHS Policy AWRs 

IACUC Minutes • Records of attendance, • Records of attendance, activities 

activities and deliberations and deliberations 

Protocols • Records of proposed • Records of proposed activities 

activities using animals using animals 

• Record of proposed • Record of proposed 

significant changes significant changes 

• Outcome of IACUC review • Outcome of IACUC review 

Basic • Semiannual IACUC reports • Semiannual IACUC reports 

Documents and recommendations and recommendations 

• Assurance Document 

• Records of accrediting 

body determinations 

Animal • Refer to Guide regarding • Records on acquired live dogs/ 

clinical records, pedigree cats or offspring including seven 

information, standardized types of information 

nomenclature, etc. • Records on dogs/cats transported/ 

sold/euthanized including three 

types of information 

• “Random Source” Certificates 

(See 2.133 (f) and (g)) 

Other • All records must be kept for • All records must be kept for 

Requirements three years; records that 

relate to applications, 

three years; records that relate 

to applications, proposals, and 

proposals, and proposed proposed significant changes 

significant changes must must be maintained for the duration 

be maintained for the of the activity plus three years. 

duration of the activity • Accessible to APHIS and Federal 

plus three years. agency officials 

• Accessible for inspection or • USDA may extend the records 

copying by OLAW or other retention requirements pending 

PHS officials completion of an investigation. 

Reference Policy IV.E. 9 CFR Part 2, Subpart C 2.35 
E.1. Recordkeeping and Reporting 175 

E.1. Table B. Federal Requirements: Assurance and Registration 

PHS Institutional USDA Research Facility 

Assurance Registration 

When required • To receive PHS support for 

animal activities 

• Approved for up to five years 

Submit to • Office of Laboratory Animal 

Welfare (OLAW) 

Submitted by • IO 

Forms • Institutional letterhead 

Contents • List all components of institution to be included, including 

sq. ft. of each facility, species 

housed and average daily 

inventory by species 

• Describe lines of authority 

and responsibility 

• List qualifications, responsibility, 

authority and percent of time 

contribution of each veterinarian 

• IACUC membership list and 

description of IACUC procedures 

• Describe occupational health 

program 

• Synopsis of training/instruction 

offered to personnel involved 

with animals 

After submission • Indicate AAALAC accreditation 

and include semiannual IACUC 

report if not accredited 

• OLAW may negotiate changes 

before approval 

Reference PHS Policy IV.A. 

• 

• 

• 

• 

• 

• 

• 

• 

• 

Animals covered by USDA 

Regulations held or used 

for regulated purposes 

Updated every three years 

APHIS, AC Regional Director 

Signed by person with legal 

authority to bind organization 

APHIS Form 7011 

Location of research facilities 

Number of covered species 

used annually 

Sources of Federal funds 

Notify APHIS via AC Regional 

Director within ten (10) days of 

change of operation 

9 CFR Part 2, Subpart C 2.30 
176 E. Recordkeeping and Communications 

E.1. Table C. Federal Requirements: Report of 

Semiannual Evaluations 

PHS Semiannual Report USDA Semiannual Report 

Timetable • Every six months; • Every six months; 

an AAALAC report may an AAALAC report may 

fulfill these requirements fulfill these requirements 

Submit to • IO • IO 

Submitted by • IACUC, as Committee action • IACUC; signed by a majority 

of members 

Form used • Not specified • Not specified 

Contents • Describe adherence to Guide • Describe adherence to AWRs 

and PHS Policy and departures and departures from AWRs; 

from Guide and PHS Policy • State reasons for departures; 

• State reasons for departures; identify significant and minor 

identify significant and minor deficiencies; include plan/schedule 

deficiencies; include plan/ to correct deficiencies; include 

schedule to correct deficiencies; minority views 

include minority views • Reviewed and signed by majority 

• Approved by IACUC of IACUC members 

• Maintained by institution • Maintained by Research Facility 

• Available to OLAW upon request Available to APHIS and funding 

• Other: Identify facilities accred- agency upon request 

ited by AAALAC • Other: Report failure to adhere 

to plan/schedule through IO 

to APHIS and funding agency 

within 15 working days 

Reference PHS Policy IV.B.3. IV.E.1.d & IV.F.4. 9 CFR Part 2, Subpart C 2.31 (c) (3) 
E.1. Recordkeeping and Reporting 177 

E.1. Table D. Federal Requirements: Annual Report 

PHS Annual Report USDA Annual Report 

Timetable • At least once every 12 months; • On or before December 1, 

may be synchronized with USDA describing activity during fiscal 

or AAALAC reporting period year (October 1–September 30) 

Submit to • OLAW • APHIS, AC Regional Director 

Submitted by • IACUC, through the IO • Signed or certified by CEO or IO 

Form used • Not specified; may use OLAW • APHIS Form 7023 

sample format provided 

Contents Report changes in: • Location of all facilities 

• AAALAC accreditation status • Endorse assurance statements 

• Animal care/use program • Common name and number of 

(as described in Assurance) animals being bred, conditioned or 

• IACUC membership in holding not being used (col. B) 

• IO • Common name and number of 

• Report date(s) IACUC animals used where: 

conducted semiannual – Animals experience no pain 

evaluations and sub- or distress (col. C) 

mitted reports to IO. – Drugs were used to alleviate 

Include any minority pain or distress (col. D) 

views of IACUC members. – Drugs were not used to 

alleviate pain or distress 

because drugs would have 

interfered with the results or 

interpretation of the procedure 

(col. E) 

• An explanation of column E 

procedures, as justified by 

the investigator and approved 

by the IACUC, must be summarized in an attachment. It 

must include species and 

number of animals affected. 

Reference PHS Policy IV.F.1, 2 & 4. 9 CFR Part 2, Subpart C 2.36 
178 E. Recordkeeping and Communications 

E.1. Table E. Federal Requirements: Suspensions 

and Noncompliance 

PHS Suspension/ USDA Suspension 

Noncompliance Report Report 

Submitted by • IACUC through IO 

Submit to • OLAW 

When required • Suspension of an activity by 

the IACUC 

• Serious deviation from the Guide 

(unless previously approved by 

the IACUC) 

• Serious or continuing noncompliance with the PHS Policy 

Contents • Full explanation of circumstances 

• Description of corrective action 

taken 

• Minority views filed by IACUC 

Reference PHS Policy IV.C.6. & 7. and IV.F.3. & 4 

• IO with IACUC consultation 

• APHIS and federal agency 

funding the activity 

• Suspension of an activity 

by the IACUC 

• Full explanation 

of circumstances 

• Description of corrective 

action taken 

9 CFR Part 2, Subpart C 2.31(d)(7) 

References 

AAALAC International. Connection Newsletter Summer 2000, pages 1-4. 

Potkay, S., et al. Frequently Asked Questions about the Public Health Service Policy 

on Humane Care and Use of Laboratory Animals. Contemporary Topics 36(2)47-50, 

March, 1997. 

NIH Guide to Grants and Contracts. Notice OD-00-007, 12/21/99. 
E.2. Communications 

It has never been easier to communicate with others, and at the beginning 

of the 21st century the use of nontraditional means of communication such 

as electronic mail (email), Web sites, and Internet chat rooms provide new 

opportunities for rapid communication. 

Electronic communication offers advantages and disadvantages. Modes of 

communication available to the IACUC vary in speed and ease of use, 

clarity, and security. Some permit easy communication with an entire committee or an entire institution; and some include a permanent record that 

can be retained for later reference. 

Regulations and Policies 

Most of the regulations governing the IACUC were written before the Internet 

became pervasive, but OLAW has presented some guidelines for the IACUC 

regarding the use of email and similar modes of communication (Garnett 

and Potkay, ILAR Journal 37:190-192, 1995). 

The guidelines state that email is an appropriate medium for transmitting 

animal protocols, IACUC meeting agenda and minutes, institutional 

policies, and other matters related to the animal care and use program. 

However, OLAW states that the conduct of IACUC meetings should allow 

greater opportunity for members to interact than that permitted by email. 

Sequential, one-on-one communication (polling) by email, telephone, or fax 

should not take the place of a convened IACUC meeting or voting, although 

it is an appropriate mechanism for providing all IACUC members with the 

opportunity to call for full committee review of a protocol prior to initiating 

the designated reviewer method of protocol review. OLAW recommends 

that traditional meetings, in which a quorum of IACUC members is in 

the same room, should be the standard method for conducting IACUC 

business such as protocol review, review of annual and semiannual reports, 

and suspensions. 

Under “exceptional circumstances” an IACUC may be permitted to 

conduct a meeting using electronic conferencing such as telephone or 

audio-visual conferences. To be considered a valid convened meeting, 

179 
180 E. Recordkeeping and Communications 

the alternate approach must include a high degree of interactivity and 

allow for careful consideration of issues. Each member must be in direct 

communication with every other member in attendance, and a quorum 

of actively participating members must be maintained. Minutes of an 

electronic conference would be written and retained as for any other convened IACUC meeting. 

If the IACUC wishes to use electronic methods for IACUC meetings or 

other activities, the proposed procedures should be described in the institutional Assurance and approved by OLAW. 

Efficiency and Security 

Email and the Internet have dramatically increased the speed and volume 

of information conveyed. Many institutions publish animal use policies and 

forms on a public Web site, and some include information such as IACUC 

membership and meeting times. Some have also developed mechanisms 

for submitting animal use protocols or modifications electronically, which 

can potentially eliminate tedious data entry and facilitate review and approval, and recordkeeping. 

The increasing use of email for communication with investigators and the 

IACUC also has the potential for speeding up the review process, provided 

that messages do not get lost in a barrage of email from other sources. 

Undoubtedly, more institutions will automate protocol submission and move 

toward more efficient review processes during the next decade. 

The continued development of electronic or digital signatures and password-only access to certain information is important. There is a widespread 

concern that electronic systems are not secure. IACUC databases should 

be maintained on institutional intranets, as opposed to the Internet, to minimize the vulnerability of systems. As Internet security improves, these 

issues should become less of an obstacle to the use of electronic communication for carrying out work of the IACUC. 

Reference 

Garnett, N. and S. Potkay. Use of Electronic Communications for IACUC Functions. 

ILAR Journal 37(4)190-192, 1995 
Appendices


181
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Appendix A: Resources 

ALTWEB


Web: http://altweb.jhsph.edu


ALTWEB is a Website created under the auspices of the Johns Hopkins 

Center for Alternatives to Animal Testing that is dedicated to providing 

information about and fostering the development of scientifically acceptable alternatives to the use of animals in testing and research. Alternatives 

are defined as methods that reduce animal use, replace whole animal tests, 

or refine existing tests by minimizing animal distress. 

American Association for Laboratory Animal Science (AALAS) 

9190 Crestwyn Hills Drive


Memphis, TN 38125


Tel: 901-754-8620


Fax: 901-753-0046


Web: http://www.aalas.org/


AALAS is an association of over 9,300 individuals dedicated to the humane


care and treatment of laboratory animals and to quality research. It serves


as a forum for the exchange of information and expertise in the care and


use of laboratory animals.


American College of Laboratory Animal Medicine (ACLAM) 

Web: http://www.aclam.org/index.html 

The ACLAM is an organization of board certified veterinary medical specialists who are experts in the humane, proper and safe care and use of 

laboratory animals. ACLAM establishes standards of education, training, 

experience and expertise necessary to become qualified as a specialist 

and recognizes that achievement through board certification. ACLAM 

promotes the advancement of knowledge in this field through professional continuing education activities, and the development of educational materials. 

183 
184 Appendix A: Resources 

American Society of Laboratory Animal Practitioners (ASLAP) 

11300 Rockville Pike


Suite 1211


Rockville, MD 20852


Tel: 301-231-6349


Fax: 301-231-6071


Email: aslap@aaalac.org


Web: http://www.aslap.org/


The ASLAP is an organization of veterinarians and veterinary students that


promotes the acquisition and dissemination of education and training in


the practice of laboratory animal medicine.


American Veterinary Medical Association (AVMA) 

1931 North Meacham Road


Suite 100


Schaumburg, IL 60173


Tel: 847-925-8070


Fax: 847-925-1329


Email: avmainfo@avma.org


Web: http://www.avma.org


The AVMA, a not-for-profit national association of veterinarians, was estab­


lished in 1863 and has a current membership representing approximately


85% of the veterinary medical profession. The Association aims to advance


the science and art of veterinary medicine, including its relationship to pub­


lic health, biological science, and agriculture. It provides a forum for the


discussion of issues of importance to the veterinary profession, and for the


development of official positions. The Association is the authorized voice


for the profession in presenting its views to government, academia, pet


owners, the media, and other concerned publics.

Appendix A: Resources 185 

Animal Welfare Information Center (AWIC) 

National Agricultural Library, USDA


10301 Baltimore Avenue, 5th Floor


Beltsville, MD 20705-2351


Tel: 301-504-6212


Fax: 301-504-7125


Email: awic@nal.usda.gov


Web: http://www.nal.usda.gov/awic/


AWIC, a component of the USDA National Agricultural Library, is


dedicated to providing information for improved animal care and use


in research, teaching, and testing. AWIC also offers educational activi­


ties that are geared towards meeting the information requirements of


the Animal Welfare Act, and publishes bibliographies, information resource


guides, and other publications.


Applied Research Ethics National Association (ARENA) 

132 Boylston Street


Fourth Floor


Boston, MA 02116


Tel: 617-423-4112


Fax: 617-423-1185


Email: PRMR@aol.com


Web: http://www.arena.org/


ARENA is a membership organization for those involved in the day-to-day


application of ethical principles, governmental regulations, and other


policies regarding research and clinical practice. ARENA services include


sponsorship of national and regional meetings, the dissemination of current


information on research ethics, and the provision of opportunities for net-


working among members through a quarterly newsletter.

186 Appendix A: Resources 

Association for Assessment and Accreditation of Laboratory Animal Care International 

(AAALAC International) 

11300 Rockville Pike


Suite 1211


Rockville, MD 20852-3035


Tel: 301-231-5353


Fax: 301-231-8282


Email: accredit@aaalac.org


Web: http://www.aaalac.org/


AAALAC International is a private, non-profit organization that promotes


the humane treatment of animals in science through a voluntary accredita­


tion program. The rigorous, peer review of the animal care and use program


promotes scientific validity and demonstrates accountability. AAALAC also


offers independent program status evaluations to assist institutions in


determining their preparedness for accreditation and to help institutions


improve their animal care and use program.


Canadian Council on Animal Care (CCAC) 

315-350 Albert Street


Ottawa ON K1R 1B1


Tel: 613-238-4031


Fax: 613-238-2837


Email: lroach@bart.ccac.ca


Web: http://www.ccac.ca/english/welcome.htm


CCAC is the national peer review agency responsible for setting and main­


taining standards for the care and use of animals used in research, teaching


and testing throughout Canada. CCAC guidelines and publications provide


useful information for animal care and use committees concerning opti­


mal physical and psychological care of animals according to acceptable


scientific standards.

Appendix A: Resources 187 

Center for Alternatives to Animal Testing 

Johns Hopkins University School of Hygiene and Public Health


111 Market Place, Suite 840


Baltimore, MD 21202-6709


Tel: 410-223-1612


Fax: 410-223-1603


Email: caat@jhsph.edu


Web: http://caat.jhsph.edu


Foundation for Biomedical Research (FBR) 

818 Connecticut Avenue, NW


Suite 303


Washington, DC 20006


Tel: 202-457-0654


Fax: 202-457-0659


Email: info@fbresearch.org


Web: http://www.fbresearch.org/index.html


The FBR was established in 1981 to improve the quality of human and ani­


mal health by promoting public understanding and support of the ethical


use of animals in scientific and medical research. FBR produces a wide


variety of educational resources to help the general public understand why


animals are so important in the search for new and better ways to treat the


diseases that afflict both people and animals.


IACUC.ORG


Web: http://www.iacuc.org/


IACUC.ORG is an information resource developed by AALAS for members and staff of institutional animal care and use committees. It is a link 

archive where online resources are organized by menus and submenus, 

which serve as organizing tools enabling users to quickly point to a topic 

of interest, such as example protocol forms or disaster plans used by 

other institutions. 
188 Appendix A: Resources 

Institute for Laboratory Animal Resources (ILAR) 

2101 Constitution Avenue, NW


Washington, DC 20418


Tel: 202-334-2590


Fax: 202-334-1687


Email: ILAR@nas.edu


Web: http://www4.nas.edu/cls/ilarhome.nsf


A component of the National Academy of Sciences, ILAR is responsible for


authoritative reports on subjects of importance to the animal care and use


community, and for serving as a clearinghouse for information about animal


resources. Its mission is to develop and make available scientific and


technical information on laboratory animals and other biological research


resources to the scientific community, the federal government, and the public.


NETVET Veterinary Resources


Web: http://netvet.wustl.edu/vet.htm


NETVET is a comprehensive website that categorizes and organizes veterinary medical and animal-related information on the Internet in a relevant, 

user friendly format. Much of the information is of interest to IACUCs. 

Office of Laboratory Animal Welfare (OLAW) 

National Institutes of Health


RKL1, MSC 7982


6705 Rockledge Drive


Bethesda, MD 20892-7982


Tel: 301-496-7163


Fax: 301-402-2803


Email: olaw@od.nih.gov


Web: http://grants.nih.gov/grants/olaw/olaw.htm


OLAW is responsible for the administration and implementation of the


Public Health Service (PHS) Policy on Humane Care and Use of Laboratory


Animals. Located at the National Institutes of Health, OLAW administers an


educational program for PHS-supported institutions and investigators,


negotiates Animal Welfare Assurances, and evaluates compliance with the


PHS Policy.

Appendix A: Resources 189 

Public Responsibility in Medicine and Research (PRIM&R) 

132 Boylston Street


Fourth Floor


Boston, MA 02116


Tel: 617-423-4112


Fax: 617-423-1185


Email: PRMR@aol.com


Web: http://www.primr.org/


PRIM&R is a national nonprofit organization dedicated to educating the


medical and legal professions, industry and the public about the ethical,


legal, and policy dimensions of appropriate and ethical research. Through


PRIM&R conferences a broad range of issues regarding research, clinical


practice, ethics, and the law are addressed, including the operation of Insti­


tutional Animal Care and Use Committees.


Scientists Center for Animal Welfare (SCAW) 

7833 Walker Drive, Suite 410


Greenbelt, MD 20770


Tel: 301-345-3500


Fax: 301-345-3503


Email: info@scaw.com


Web: http://www.scaw.com/


The SCAW is a non-profit educational association of individuals and institu­


tions whose mission is to promote humane care, use, and management of


animals involved in research, testing or education in laboratory, agricultural,


wildlife or other settings. It offers an ongoing forum for the exchange and


evaluation of scientific information about the care, treatment, well-being


and ethical use of animals.

190 Appendix A: Resources 

United States Department of Agriculture (USDA), Animal Care (AC) 

4700 River Road, Unit 84


Riverdale, MD 20737-1234


Tel: 301-734-7833


Fax: 301-734-4978


Email: ace@aphis.usda.gov


Web: http://www.aphis.usda.gov/ac/


The Animal Care (AC) component of the USDA’s Animal and Plant Health


Inspection Service (APHIS) is responsible for the enforcement of the Animal


Welfare Act (AWA). The AWA sets minimum standards of care and treat­


ment for most warm-blooded animals used in research. Three regional


offices employ field veterinary medical officers (VMOs) who regularly


conduct unannounced inspections of research facilities for compliance with


the USDA animal welfare regulations.


University of California Center for Animal Alternatives (UCCAA) 

One Shields Avenue


Davis, CA 95616-8684


Tel: 530-752-1800


Fax: 530-754-8606


Email: animalalternatives@ucdavis.edu


Web: http://www.vetmed.ucdavis.edu/Animal_Alternatives/main.htm


The UCCAA collects, disseminates, and facilitates access to information


concerning animal alternatives, serving primarily the scientists and staff on


the nine University of California campuses. The purpose is to improve the


well-being and quality of life of research animals, but also to optimize their


contribution to education and research.


ResearchTraining.org


Web: http://www.researchtraining.org


ResearchTraining.org is a Website developed by the Medical Research 

Service in the VA Office of Research and Development. Its purpose is to 

help VA and non-VA institutions meet research training mandates. The 

site includes free web-based courses and exams for research staff and 

IACUC members, and an IACUC Administrator’s site where administrators 

can review the records of staff members who pass exams. 
Appendix B: Office of Laboratory Animal Welfare


NATIONAL INSTITUTES OF HEALTH 

Director 

Office of Extramural Research 

Deputy Director of Extramural Research 

Office of Laboratory Animal Welfare 

Director 

Division of Assurances 

Director 

Division of Compliance 

Oversight 

Director 

191

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Appendix C:	 Mandatory IACUC Issues Identified During

AAALAC International Site Visits 

(See Section B.1. Program and Facility Review) 

• Inadequate review and follow-up of the animal care and use program 

• Need for more rigorous protocol review 

• Inadequate records of IACUC activities 

• Assurance of participation in and adequacy of training programs 

• Inadequately addressing issues pertaining to pain and distress 

• Need for IACUC to review and approve deviations from the Guide 

• IACUC assurance of adequate veterinary care 

• Inadequate IACUC oversight of animals in satellite/contract facilities 

• Committee composition and participation 

• Changes in protocol without IACUC review and approval 

•
 No three year complete review of protocols/annual review of PHSfunded research 

• Allowing ordering of animals without assignment to an animal use protocol 

• Not all animals covered by a protocol (e.g., breeding animals) 

•
 Absence of exercise and psychological well-being plans for dogs and 

nonhuman primates 

• Committee not appointed by the CEO 

• Inadequate facility inspections (e.g., laboratories) 

• Inadequate training of IACUC 

• Inadequate intensity of oversight of program 

Presented in order of most common citation to least frequent citation. 

193 
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Appendix D: Recommendations of the 2000 AVMA Panel 

on Euthanasia 

(See C.2.b. Euthanasia) 

The 2000 AVMA Panel on Euthanasia Report characterizes euthanasia 

methods by type: 

1) Inhalant agents, 

2) Noninhalant pharmaceutical agents, and 

3) Physical methods. 

The Panel further classifies the methods into those that are considered 

acceptable, conditionally acceptable and unacceptable when used as the 

sole means of euthanasia. 

Euthanasia of Homeothermic (Warm-blooded) Animals 

Inhalant Agents 

Inhalant Anesthetics: The Panel recommends the use of halothane, enflurane, 

sevoflurane, methoxyflurane, isoflurane and desflurane (in order of prefer•

ence) for animals under 7 kg. Although acceptable for use in larger animals 

these agents are not often used due to cost and difficulty in administration. 

Induction with methoxyflurane (metofane) is unacceptably slow in some 

species. Ether was formerly used extensively, but is now only conditionally 

acceptable due to irritation of mucous membranes and risk of fire and 

explosion. Nitrous oxide (N2O) does not produce anesthesia, and may 

produce hypoxemia and cardiac or respiratory arrest. It may be used in 

combination with other anesthetics to speed anesthesia onset. It is impor•

tant to minimize exposure of personnel to these potentially toxic agents; 

therefore fume hoods must be used. 

195 
196 Appendix D: Recommendations of the 2000 AVMA Panel on Euthanasia 

Carbon Dioxide (CO2): Carbon dioxide is an effective and widely used agent 

to euthanize rodents. This method causes hypoxia attributable to depres•

sion of vital centers. Use of carbon dioxide generated by other methods 

(e.g., dry ice, fire extinguishers) is not acceptable. Compressed CO2 gas in 

cylinders is the only recommended source of carbon dioxide, since the inflow to the euthanasia chamber can be regulated. An optimal flow rate will 

displace at least 20% of the chamber volume per minute. In some species 

(e.g., rats) prefilling the chamber to 70% or more will produce rapid uncon•

sciousness with minimal distress. Young animals, and some burrowing and 

diving animals, are relatively resistant to the hypoxemic effect of CO2. Since 

the effects of carbon dioxide are reversible, it is important to ensure that the 

animals are dead. 

Other agents: Nitrogen and argon are listed as conditionally acceptable 

methods for death by hypoxemia, and are relatively safe. Although effec•

tive, they may cause distress and other methods are preferred. Carbon 

monoxide induces unconsciousness without significant discomfort, and is 

considered acceptable for euthanasia for dogs, cats, and other small mam•

mals. However, it is dangerous to use, and the Panel recommends it only if 

proper precautions are observed. 

Non-inhalant Agents 

Barbiturates: Injection of barbiturates, particularly sodium pentobarbital, is 

the most rapid and reliable method of euthanasia for most research 

animals. In non-rodent species, barbiturates are given intravenously to be 

most effective. A sedative or tranquilizer may be given prior to the barbi•

turate in animals that are difficult to restrain. Intraperitoneal injection is also 

acceptable when necessary if restraint or intravenous administration would 

be more stressful. In rodents, intravenous barbiturate for euthanasia is not 

common, since equally humane and less time-consuming methods are available. Intraperitoneal injection of barbiturate is acceptable for euthanasia in 

small mammals. 

Sodium pentobarbital is listed as a Schedule II drug by the U.S. Drug 

Enforcement Administration (DEA). Current federal drug regulations require 

strict accounting for barbiturates, and they must be used under the supervision of personnel registered with the DEA. Some effective euthanasia 

solutions contain barbiturates in combination with other agents, and are 

listed Schedule III and are less restricted in use. 
Appendix D: Recommendations of the 2000 AVMA Panel on Euthanasia 197 

Potassium Chloride (KCl): KCl induces immediate cardiac arrest without 

any significant depression of the central nervous system. Hence, it must 

only be used after the animal is deeply anesthetized. 

Neuromuscular Blocking Agents (Succinycholine, Curare, etc.): These drugs 

induce muscular paralysis and death by suffocation. They are not acceptable for euthanasia. 

Physical Methods 

Physical methods are sometimes necessary to obtain scientifically valid data 

and, while aesthetically displeasing to some individuals, are humane when 

properly performed by skilled and experienced personnel with appropriate, 

well-maintained equipment. The Panel considers most physical methods to 

be conditionally acceptable. 

Cervical Dislocation: This is frequently used for mice, poultry and other small 

birds, immature rats weighing less than 200 grams and rabbits weighing 

less than one kilogram. Cervical dislocation is described in the 2000 AVMA 

Report as a humane technique for euthanasia of rodents and small rabbits 

in research, which induces rapid loss of consciousness without chemically 

contaminating tissue. Its use must be scientifically justified and approved 

by the IACUC on a case-by-case basis. As part of the approval process the 

IACUC must be assured that the personnel are appropriately qualified in 

the use of this method for the specific species involved. It is critical that 

personnel performing these procedures are thoroughly trained, usually by 

practicing the procedure on anesthetized animals. 

Decapitation: Decapitation may be used to euthanize rodents and small 

rabbits. Except in neonatal animals, a guillotine is generally used. The sec•

tion should be through the atlanto-occipital joint. The 2000 AVMA Report 

recommends that decapitation be done only when scientifically justified and 

approved by the IACUC on a case-by-case basis. As part of the approval 

process the IACUC must be assured that the personnel are appropriately 

skilled in the use of this method for the specific species involved. 

Microwave Irradiation: This method is used when a project requires fixation 

of mouse or rat brain metabolites in vivo without losing anatomic integrity of 

the brain. Commercial microwave chambers will render a rodent uncon•

scious in less 100 msec. and dead in under one second. These instruments 

differ from household units in that they direct most of the microwave energy 

at the head of the animal. Only instruments designed for this purpose and 

having the appropriate power and microwave distribution may be used. 
198 Appendix D: Recommendations of the 2000 AVMA Panel on Euthanasia 

Penetrating Captive Bolt: This method is conditionally acceptable for 

ruminants, horses, and swine when chemical agents are scientifically 

contraindicated. Use of a non-penetrating captive bolt only stuns and should 

not be attempted as the sole means of euthanasia. 

Euthanasia of Poikilothermic (Cold-blooded) Animals 

The 2000 Report of the AVMA Panel on Euthanasia addressed the euthana•

sia of poikilothermic animals and in doing so pointed out that the available 

objective information on these species in the literature limits the guidelines 

that can be developed. The Panel also pointed out the differences in the 

metabolism, respiration and tolerance to cerebral hypoxia between these 

species and homeothermic animals must be considered when selecting a 

method of euthanasia. 

Chemical Agents: Intraperitoneal administration of pentobarbital is an 

effective method of euthanasia in amphibians, turtles and snakes. Tricaine 

methane sulfonate (MS222) or benzocaine hydrochloride may be placed in 

the water of amphibians and fish to produce anesthesia and prolonged contact will produce death. Inhalant anesthetics may be used for amphibians 

and reptiles. Due to the low oxygen requirements for reptiles, the onset of 

unconsciousness and death will be significantly lengthened. 

Physical Methods: Poikilotherms may be euthanized by stunning followed 

by decapitation, pithing, or some other method to ensure death. In frogs 

and toads, pithing the brain and spinal cord (double pithing) is an effective 

and acceptable method. 

Additional and Adjunctive Methods 

The 2000 Report of the AVMA Panel on Euthanasia included additional 

methods that, under appropriate circumstances, would produce a humane 

death. For specifics, consult the Panel report published in JAVMA Vol. 218, 

No. 5, March 1, 2001. 
Appendix E:	 Federal and State Permits Required for

Field Studies 

(See Section C.3.d. Field Studies) 

One research protocol may be subject to multiple laws and therefore 

multiple permits might be required. It is most commonly the case that 

both state and federal permits are needed in addition to site-specific 

permits for research conducted on federal- or state-owned property. 

U.S. Fish and Wildlife Service 

The permits administered by the U.S. Fish and Wildlife Service (USFWS) 

are found in 50 CFR, Sections 1 - 100. The general permit conditions found 

in 50 CFR 13 state that any person accepting and holding a permit 

acknowledges the necessity for close regulation and monitoring of the 

permitted activity by the Government. By accepting such permit, the per•

mittee consents to and must allow entry by agents or employees of the 

USFWS upon premises where the permitted activity is conducted at any 

reasonable hour. Service agents or employees may enter such premises to 

inspect the location; any books, records, or permits required to be kept by 

this subchapter; and any wildlife or plants kept under authority of the per•

mit. The regulations also provide for permit suspension and revocation if 

permit terms and conditions are violated. 

USFWS has developed a system to assess the impact of permitted acti•

vities on populations. Known as the Service-wide Permits Issuance 

and Tracking system, this tool allows permit biologists to determine the 

cumulative impact of permitted activities on wildlife populations with a high 

degree of precision. 

To take, possess, or transport any bald eagle (Haliaeetus leucocephalus) or 

any golden eagle (Aquila chrysaetos), or the parts, nests, or eggs of such 

birds, a Bald and Golden Eagle Protection Act permit is required, although 

banding and marking may be authorized under a Migratory Bird Treaty Act 

permit. The USFWS will accept a single application for both permits 

provided that it includes all of the information required for an application 

under each applicable part. 

199 
200 Appendix E: Federal and State Permits Required for Field Studies 

CITES 

The Convention on International Trade in Endangered Species, commonly 

referred to by the acronym CITES, is an international treaty codified in U.S. 

law as part of the Endangered Species Act. It regulates import and export 

of wildlife and plants listed on its three appendices. Appendix I species 

require both an export permit from the country of origin and an import 

permit from the importing country. Commercial trade is prohibited but 

import and export for scientific research is allowed, subject to very strict 

permitting requirements. Permit issuance criteria require capture and 

import methods that minimize the risk of injury, damage to health or cruel 

treatment. Permits are not issued if the proposed import or export would be 

detrimental to the survival of the species. 

Endangered Species Act 

The Endangered Species Act prohibits the taking of any species listed as 

endangered or threatened. The endangered species list is found in 50 CFR 

17.11. The term “take” means to harass, harm, pursue, hunt, shoot, wound, 

kill, trap, capture, or collect, or to attempt to engage in any such conduct. 

Both civil and criminal penalties can be imposed on a violator. Exceptions 

are made for scientific research and for activities that will enhance the 

survival of the species. Permits are required for such activities and are 

issued by the USFWS (except in the case of marine mammals and 

fishes, which are issued by the National Marine Fisheries Service). The regu•

lations governing scientific permits for endangered species are found at 

50 CFR 17.22; regulations for permits for threatened species are found 

at 50 CFR 17.62. 

In considering whether to grant a permit, the permitting official will consider 

the purpose for which the permit is required, the probable direct and 

indirect effect on the population of issuing the permit, whether the permit 

would conflict with programs intended to enhance the survival probabilities 

of the population, whether the permit would reduce the threat of extinction, 

opinions or views of experts in matters germane to the application, and 

whether the expertise, facilities, or other resources available to the appli•

cant appear adequate to successfully accomplish the objectives stated 

in the application. 
Appendix E: Federal and State Permits Required for Field Studies 201 

An issued permit may contain conditions that the permitting authority 

chooses to impose, including requirements for humane conditions (50 CFR 

13.41). For instance, the permit may limit the time a researcher may spend 

in a colony of seabirds, limit capture methods, or otherwise dictate limits on 

research methodology. Applications for endangered species permits are 

published in the Federal Register and afford the public an opportunity to 

comment or object. 

Lacey Act 

The original Lacey Act dates back to 1900; what is currently referred to as 

the Lacey Act is actually the Lacey Act Amendments of 1981. It is not spe•

cific to research, but pertains to research involving the import and export of 

wildlife. Most commonly, the import and export of wildlife is conducted by 

museums acquiring or trading specimens but there is also importation and 

exportation of live animals for research purposes. The law covers all fish 

and wildlife and their parts or products. Under this law, it is unlawful to 

import, export, sell, acquire, or purchase fish, wildlife or plants taken, pos•

sessed, transported, or sold: 1) in violation of U.S. or Indian law, or 2) in 

interstate or foreign commerce involving any fish, wildlife, or plants taken, 

possessed or sold in violation of State or foreign law. 

Regulations pertaining to the import, export, and transportation of wildlife are found at 50 CFR 14. Generally, wildlife must be imported through 

designated ports in order to allow for inspection by Customs officers and/ 

or USFWS law enforcement officers. Permits can be obtained to import 

wildlife for scientific purposes through nondesignated ports. Otherwise, for 

import of species not listed on CITES or the Endangered Species List, 

importers or their agents must file with the Service a completed Declaration 

for Importation or Exportation of Fish or Wildlife (Form 3-177), signed by the 

importer or the importer’s agent, upon the importation of any wildlife at 

the place where Service clearance (permission for release from the port) 

is requested. 

Marine Mammal Protection Act 

The 1972 Marine Mammal Protection Act established a Federal responsibil•

ity to conserve marine mammals with management vested in the Depart•

ment of Interior for sea otter, walrus, polar bear, dugong, and manatee. The 

Department of Commerce is responsible for cetaceans and pinnipeds, other 

than the walrus. With certain specified exceptions, the Act establishes a 
202 Appendix E: Federal and State Permits Required for Field Studies 

moratorium on the taking and importation of marine mammals as well 

as products taken from them, and establishes procedures for waiving the 

moratorium and transferring management responsibility to the States. The 

1988 amendments include the listing of conditions under which permits 

may be issued to take marine mammals for the protection and welfare of 

the animals, including importation, public display, scientific research, and 

enhancing the survival or recovery of a species. 

Scientific permits are provided for by 50 CFR 18. If the application is for 

a scientific research permit, it must include a detailed description of the 

scientific research project or program in which the marine mammal or 

marine mammal product is to be used including a copy of the research 

proposal relating to such program or project and the names and addresses 

of the sponsor or cooperating institution and the scientists involved. Where 

the species is listed as endangered or threatened or has been designated 

as depleted, the applicant must also provide a detailed justification of the 

need for such a marine mammal, including a discussion of possible alterna•

tives, whether or not under the control of the applicant. 

Migratory Bird Treaty Act 

The original 1918 statute implemented the 1916 Convention between the 

U.S. and Great Britain (for Canada) for the protection of migratory birds. 

Specific provisions in the statute include the establishment of a federal 

prohibition, unless permitted by regulations, to “pursue, hunt, take, cap•

ture, kill, attempt to take, capture or kill, possess, offer for sale, sell, offer to 

purchase, purchase, deliver for shipment, ship, cause to be shipped, 

deliver for transportation, transport, cause to be transported, carry, or cause 

to be carried by any means whatever, receive for shipment, transporta•

tion or carriage, or export, at any time, or in any manner, any migratory bird, 

included in the terms of this Convention . . . for the protection of migratory 

birds . . . or any part, nest, or egg of any such bird.” (16 U.S.C. 703) 

The Secretary of the Interior is authorized to determine, periodically, when, 

consistent with the Conventions, “hunting, taking, capture, killing, posses•

sion, sale, purchase, shipment, transportation, carriage, or export of any . . . 

bird, or any part, nest or egg” could be undertaken and to adopt regulations 

for this purpose. 
Appendix E: Federal and State Permits Required for Field Studies 203 

The title “Migratory Bird Treaty Act” (MBTA) is a misnomer because the Act 

does not apply only to birds that migrate long distances or across interna•

tional borders, but to nearly 830 species of birds. Permits for the taking of 

birds protected by the MBTA are found at 50 CFR 21. 

Banding and marking activities require a permit under 50 CFR 21.22. These 

permits are issued by the U.S. Geological Survey–Biological Resources 

Division’s Bird Banding Laboratory. A banding permit authorizes the 

placement of USFWS-issued bands on birds. Additional authorization is 

required for the use of auxiliary markers (such as colored leg bands, paint 

marks, wing tagging, radio transmitters), mist nets, cannon or rocket nets, 

or chemical means of capturing birds. Permits are specific to taxa or even 

species. Special authorization is required for endangered species, eagles, 

waterfowl, and hummingbirds. The Bird Banding Laboratory may also 

authorize the taking of blood and feather samples. Requests to band in 

more than one state must be justified. 

Other MBTA permits are obtained from the USFWS. These include permits 

for scientific collecting (50 CFR 21.23). The regulation does not limit the 

number of individuals that may be collected, but the USFWS by practice 

and policy does. 

Wild Bird Conservation Act 

The Wild Bird Conservation Act (WBCA) prohibits the import of any bird into 

the United States other than those specifically listed in the regulations 

as permissible. For any other species, a permit is required. This law sup•

plements CITES, as many species of birds are also listed on CITES 

Appendices I and II. 

Permits may be issued for scientific research, and are in addition to any 

other permits that might be required. So, for instance, if the species is also 

a CITES-listed species, both a CITES and a WBCA permit are required. 

The regulation for scientific research permits is found at 50 CFR 15.22. 

Applications must detail (among other things) why the applicant is justified 

in obtaining a permit, and a complete description of the scientific research 

to be conducted on the exotic bird requested. 
204 Appendix E: Federal and State Permits Required for Field Studies 

Site-specific Permit Requirements 

Site-specific permits are in addition to the permits described above. A 

permit to conduct research on federal property confers no right to conduct 

research without other legally required permits. 

Bureau of Land Management 

The Bureau of Land Management (BLM) has no specific requirements or 

permits for scientific research activities. General use regulations under 43 

CFR 2920 govern all non-federal use of the lands managed by the BLM. 

The local BLM office is to consider the duration of the anticipated use and 

its impact on the public lands and resources. Permission will be given only 

for those uses that conform with BLM plans, policy, objectives and resource 

management programs. For some research activities, a permit may not be 

required as the regulations provide that no land use authorization is 

required under the regulations in this part for casual use of the public lands. 

An application must include a description of the proposed land use in 

sufficient detail to enable the authorized officer to evaluate the feasibility of 

the proposed land use, the impacts if any, on the environment, the public or 

other benefits from the proposed land use, the approximate cost of the 

proposal, any threat to the public health and safety posed by the proposal 

and whether the proposal is, in the proponent’s opinion, in conformance 

with BLM plans, programs and policies. 

National Parks 

National Park Service (NPS) regulations prohibit possessing, destroying, 

injuring, defacing, removing, digging, or disturbing from its natural state 

living or dead wildlife or fish, or the parts or products thereof, such as ant•

lers or nests (36 CFR 2.1.). Section 2.2 prohibits the taking of wildlife, 

except by authorized hunting and trapping activities conducted in accor•

dance with paragraph (b) of this section and the feeding, touching, teasing, 

frightening or intentional disturbing of wildlife nesting, breeding or other 

activities. Possession of a weapon, net, or trap without a permit is prohibited. 

There is no specific regulation pertaining to scientific research other than 

the collecting regulation discussed below. Currently, the NPS policy regard•

ing research is found in its Administrative Guide, which pertains to all scien•

tific research, Application Procedures and Requirements for Research and 

Collecting Permits, and the Guidelines for Study Proposals. In 1999, NPS 

began an effort to develop a research and collecting permit and reporting 
Appendix E: Federal and State Permits Required for Field Studies 205 

system. Researchers are required to submit research proposals, which are 

reviewed by the NPS for scientific validity and actual or potential impact to 

park resources, among other things. The NPS may impose any conditions it 

deems appropriate. In reviewing applications, the NPS considers, among 

other things, whether the proposed research contributes information useful 

to an increased understanding of park resources or addresses problems or 

questions of importance to science or society and shows promise of mak•

ing an important contribution to humankind’s knowledge of the subject 

matter. The qualifications of the applicant are also reviewed. 

Scientific collecting, including the taking of plants, fish, wildlife, rocks or 

minerals is regulated by 36 CFR 2.5. A specimen collection permit may be 

issued only to an official representative of a reputable scientific or educa•

tional institution or a State or Federal agency for specific purposes described 

in the regulations. A permit to take an endangered or threatened species 

listed pursuant to the Endangered Species Act, or similarly identified by the 

States, may not be issued unless the species cannot be obtained outside of 

the park area and the primary purpose of the collection is to enhance the 

protection or management of the species. In park areas where the enabling 

legislation authorizes the killing of wildlife, a permit that authorizes the kill•

ing of plants, fish or wildlife may be issued only when the superintendent 

approves a written research proposal and determines that the collection 

will benefit science or has the potential for improving the management and 

protection of park resources. In park areas where enabling legislation does 

not expressly prohibit the killing of wildlife, a permit authorizing the killing 

of plants, fish or wildlife may be issued only when the superintendent 

approves a written research proposal and determines that the collection 

will not result in the derogation of the values or purposes for which the park 

area was established and has the potential for conserving and perpetuat•

ing the species subject to collection. In park areas where the enabling 

legislation prohibits the killing of wildlife, issuance of a collecting permit 

for wildlife or fish or plants, is prohibited. 

National Forests 

Forest Service laws and regulations prohibit all activities that are not 

expressly allowed by regulation or permit under 36 CFR 251, and the regu•

lations do not address scientific research specifically. The guidelines for 

special use permits are found in 36 CFR 251.54. The two-tier screening 

process entails, among other things, determinations that authorization 

of the proposed activity is consistent or can be made consistent with the 

standards and guidelines in the applicable forest land and resource 
206 Appendix E: Federal and State Permits Required for Field Studies 

management plan required under the National Forest Management Act and 

36 CFR part 219, and that the proposed activity does not materially impact 

the characteristics or functions of the environmentally sensitive resources 

or lands identified in Forest Service Handbook 1909.15, chapter 30. 

National Wildlife Refuges 

When a national wildlife refuge is created, it is considered closed to the 

public until it is expressly opened by its manager. The refuge managers 

are, under the National Wildlife Refuge System Administration Act of 1966, 

to allow “compatible” wildlife dependent recreation. In 1997, Congress 

enacted the National Wildlife Refuge System Improvement Act (NWRSIA), 

which retained the compatibility standards, but required FWS to define what 

it is and establish a process for compatibility determinations. On October 

18, 2000, the USFWS issued its Final Compatibility Regulations (65 FR 

62457-62483). The regulation defines compatibility as, “a proposed or 

existing wildlife-dependent recreational use or any other use of a national 

wildlife refuge that, based on sound professional judgment, will not materi•

ally interfere with or detract from the fulfillment of the National Wildlife 

Refuge System mission or the purpose(s) of the national wildlife refuge.” 

This determination is to be made by the refuge manager. 

The primary concern of refuge managers under the statutes and regu•

lations is to “administer a national network of lands and waters for the 

conservation, management, and, where appropriate, restoration of the fish, 

wildlife, and plant resources and their habitats within the United States for 

the benefit of present and future generations of Americans.” The NWRSIA 

specifically defines the terms ‘conserving,’ ‘conservation,’ ‘manage,’ ‘man•

aging’ and ‘management’ to mean, “to sustain, and where appropriate, 

restore and enhance, healthy populations of fish, wildlife, and plants, utiliz•

ing, in accordance with applicable Federal and State laws, methods, and 

procedures associated with modern scientific resource programs. Such 

methods and procedures include, consistent with the provisions of this Act, 

protection, research, live trapping and transplantation, and regulated taking.” 

State Laws and Regulations 

Virtually all States regulate activities involving wildlife, including scientific 

research. The Center for Wildlife Law has published a handbook entitled 

State Wildlife Laws Handbook, which covers all State wildlife statutes, al•

though it does not include permitting regulations. State regulations would 

be found in the States’ analogues to the Code of Federal Regulations. Most 

State regulations also require permits for research on State-owned lands. 
Appendix E: Federal and State Permits Required for Field Studies 207 

Professional Societies 

Animal Behavior Society


Website: http://www.animalbehavior.org/


Contact: Animal Behavior Society 

Indiana University 

2611 East 10th Street, #170 

Bloomington, IN 47408-2603 

(812) 856-5541 

American Fisheries Society


Website: http://www.fisheries.org


Contact: American Fisheries Society 

5410 Grosvenor Lane, Suite 110 

Bethesda, MD 20814-2199 

(301) 897-8616 

American Society of Ichthyologists and Herpetologists 

Website: http://199.245.200.110/ 

Contact: ASIH has no staffed office. Leadership and committee members, 

including the Animal Care and Use Committee, are listed on the 

ASIH website, which also includes an on-line directory of mem•

bers’ e-mail addresses. 

American Society of Mammalogists


Website: http://www.mammalsociety.org/


Contact: ASM has no staffed office. Leadership and committee members°

are listed on the ASM website.°
208 Appendix E: Federal and State Permits Required for Field Studies 

The Ornithological Council


Website: http://www.nmnh.si.edu/BIRDNET


Contact: The Ornithological Council 

3713 Chevy Chase Lake Drive, Apt 3 

Chevy Chase, MD 20815 

(301) 986-8568 

The Wildlife Society 

Website: www.wildlife.org 

Contact: The Wildlife Society 

5410 Grosvenor Lane 

Bethesda, MD 20814 

(301) 897-9770 

(301) 530-2471 Fax 
Appendix F:	 U.S. Government Principles for the Utilization

and Care of Vertebrate Animals Used in 

Testing, Research and Training 

The development of knowledge necessary for the improvement of the 

health and well-being of humans as well as other animals requires in vivo 

experimentation with a wide variety of animal species. Whenever U.S. Gov•

ernment agencies develop requirements for testing, research, or training 

procedures involving the use of vertebrate animals, the following principles 

shall be considered; and whenever these agencies actually perform or spon•

sor such procedures, the responsible Institutional Official shall ensure that 

these principles are adhered to: 

I.­ The transportation, care, and use of animals should be in accor•

dance with the Animal Welfare Act (7 U.S.C. 2131 et. seq.) and other 

applicable Federal laws, guidelines, and policies.* 

II.­ Procedures involving animals should be designed and performed 

with due consideration of their relevance to human or animal health, 

the advancement of knowledge, or the good of society. 

III.­ The animals selected for a procedure should be of an appropriate 

species and quality and the minimum number required to obtain 

valid results. Methods such as mathematical models, computer simu•

lation, and in vitro biological systems should be considered. 

IV. Proper use of animals, including the avoidance or minimization of 

discomfort, distress, and pain when consistent with sound scientific 

practices, is imperative. Unless the contrary is established, investi•

gators should consider that procedures that cause pain or distress 

in human beings may cause pain or distress in other animals. 

V. Procedures with animals that may cause more than momentary or 

slight pain or distress should be performed with appropriate seda•

tion, analgesia, or anesthesia. Surgical or other painful procedures 

should not be performed on unanesthetized animals paralyzed by 

chemical agents. 

VI.­ Animals that would otherwise suffer severe or chronic pain or dis•

tress that cannot be relieved should be painlessly killed at the end 

of the procedure or, if appropriate, during the procedure. 

209 
210 Appendix F: U.S. Government Principles 

VII. The living conditions of animals should be appropriate for their 

species and contribute to their health and comfort. Normally, the 

housing, feeding, and care of all animals used for biomedical pur•

poses must be directed by a veterinarian or other scientist trained 

and experienced in the proper care, handling, and use of the spe•

cies being maintained or studied. In any case, veterinary care shall 

be provided as indicated. 

VIII. Investigators and other personnel shall be appropriately qualified 

and experienced for conducting procedures on living animals. Ade•

quate arrangements shall be made for their in-service training, in•

cluding the proper and humane care and use of laboratory animals. 

IX.­ Where exceptions are required in relation to the provisions of these 

Principles, the decisions should not rest with the investigators di•

rectly concerned but should be made, with due regard to Principle 

II, by an appropriate review group such as an institutional animal 

care and use committee. Such exceptions should not be made solely 

for the purposes of teaching or demonstration. 

* For guidance throughout these Principles, the reader is referred to the Guide for the Care and 

Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National 

Academy of Sciences. 
Office of Laboratory Animal Welfare 

National Institutes of Health


Rockledge I, Suite 360, MSC 7982


6705 Rockledge Drive


Bethesda, MD 20892-7982