FEDERAL REGULATION OF BIOMEDICAL RESEARCH INVOLVING ANIMALS

FEDERAL REGULATION OF BIOMEDICAL RESEARCH INVOLVING ANIMALS Public accountability is essential to the future of biomedical research that can relieve human and animal suffering and save lives. The American public strongly supports U.S. investment in such research, considering it to be among the nation s highest priorities. Americans are also well-known for wanting animals to receive proper care and to be protected from harm. Given the public s interest in both scientific advances and animal welfare, a comprehensive system of government oversight is in place regulating the use of animals in the laboratory. National Association for Biomedical Research 818 Connecticut Avenue, NW, Suite 900 Washington DC 20006 Tel: 202.857.0540 Fax: 202.659.1902 info@nabr.org www.nabr.org

FEDERAL REGULATION OF BIOMEDICAL RESEARCH INVOLVING ANIMALS Public accountability is essential to the future of biomedical research that can relieve human and animal suffering and save lives. Even if such legal requirements did not exist, researchers know that laboratory animals must be cared for humanely for both ethical and scientific reasons. Excellent science demands excellent care of research animals. To understand more about the scientific community s dedication to the highest-quality animal care, please refer to the NABR Issue entitled Humane Care and Treatment of Laboratory Animals. Because the average person may not be aware of their existence, the following is a summary of the major laws, regulations and guidelines that must be followed when laboratory animals are used: U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training Animal Welfare Act and the U.S. Department of Agriculture Animal Welfare Regulations and Standards U.S. Public Health Service Act and Policy on Humane Care and Use of Laboratory Animals Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences Institute for Laboratory Animal Resources Good Laboratory Practice Standards of the Food & Drug and Environmental Protection Administrations Other Federal Agency requirements and Freedom of Information Act. In addition to the federal requirements above, there are many state laws and even local ordinances affecting the use of animals for research purposes. Applicable laws vary for each state. The most common states laws govern the licensing of research facilities as well as whether or not and under what circumstances animals from municipal pounds may be obtained for research. U.S. GOVERNMENT PRINCIPLES These tenets underlie the current system of federal regulation and succinctly describe the framework within which all activities involving laboratory animals must be conducted. 1

U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training i The development of knowledge necessary for the improvement of the health and wellbeing of humans as well as other animals requires in vivo experimentation with a wide variety of animal species. Whenever U.S. Government 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 sponsor 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 accordance with the Animal Welfare Act (7U.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 simulation, 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, investigators 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 sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on un-anesthetized animals paralyzed by chemical agents. 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. 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. 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. 2

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. * For guidance throughout these Principles, the reader is referred to the Guide for the Care of Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National Academy of Sciences. ANIMAL WELFARE ACT (AWA) The federal Animal Welfare Act (7 U.S.C. 2131-59) ii was enacted in 1966 and has been amended by Congress five times to expand significantly its original scope. The AWA applies to all research facilities (public or private, academic or industry-based) that use animal species covered by the Act, whether or not they receive federal funds. Currently, the species directly regulated are guinea pigs, hamsters, gerbils, rabbits, dogs, cats, nonhuman primates, marine mammals, farm animal species when used in biomedical research, and warm-blooded wild animals. Rats, mice and birds bred for research are not covered. All research facilities utilizing covered species must register with the U.S. Department of Agriculture (USDA) and comply with the AWA as proscribed in USDA-issued animal welfare regulations and standards. Each facility must report to the USDA annually, verifying compliance. The USDA is required to inspect each research facility at least annually. These inspections are unannounced. More frequent unscheduled inspections are made if significant deficiencies are identified. Registered research facilities are also required to have an Institutional Animal Care and Use Committee (IACUC) that reviews and approves proposed procedures involving animals. The IACUC inspects facilities semiannually and reviews the condition of animals to ensure compliance with the AWA and to minimize pain or distress that animals might experience. At least one member of the Committee must be a veterinarian. At least one member must be a public member, not affiliated in any way with the institution, who represents general community interests in the proper care and treatment of animals. USDA ANIMAL WELFARE REGULATIONS AND STANDARDS As required by the AWA as amended, USDA s Animal and Plant Health Inspection Service (APHIS) administers detailed regulations defining the responsibilities of research facilities, the duties of IACUCs and specific standards for animal care (9 C.F.R. Ch. 1, Parts 1, 2 and 3). iii In experimental procedures, research facilities must ensure that any animal pain or distress is minimized, including adequate veterinary care with the appropriate use of anesthetic, analgesic, tranquilizing drugs or euthanasia. Principal investigators must consider alternatives to any procedure using animals, especially those procedures likely to cause pain or distress to a laboratory animal and provide written assurance of this consideration. They must also assure that activities do not unnecessarily duplicate previous 3

experiments. Research facility personnel working with animals must have appropriate qualifications and training. Research facilities must report to USDA annually verifying compliance with the regulations and identifying the number of regulated animals used by both species and the type of procedure involved (without pain or distress, pain or distress relieved by appropriate medication or pain or distress without medication because of scientific necessity). Beyond annual reporting, research facilities are required to keep extensive records on IACUC activities (minutes of meetings, reports of biannual inspections, etc.), veterinary care and documentation of the source of animals. These records are available to USDA staff during inspection. Animal welfare standards by species include specific, detailed requirements for handling, transportation, housing, cage size, feeding, watering, sanitation, ventilation, temperature, humidity and adequate veterinary care. Research facilities also must have individualized, written plans for exercise programs for dogs and for addressing the psychological well-being of nonhuman primates. PUBLIC HEALTH SERVICE ACT In 1985 Congress passed amendments to the Public Health Service Act (42U.S.C. 289d) iv, which created a legal mandate for longstanding policies governing the use of animals supported by U.S. Department of Health and Human Services (DHHS) funds. The DHHS units that typically support animal research include the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). The legal requirements imposed by the PHS Act are similar to and consistent with the federal Animal Welfare Act. PHS Policy on Humane Care and Use of Laboratory Animals The Public Health Service (PHS) Policy on the Humane Care and Use of Laboratory Animals (Policy) v implements Congress 1985 mandate and supplements the U.S. Government Principles. It applies to all DHHS-conducted or supported research, research training, and biological testing activities involving the use of all vertebrate animals, including rats and mice. Compliance with the Policy is required for activities conducted by DHHS units and by awardee institutions as a condition of receiving DHHS funds. DHHS grants or contracts can be suspended or revoked for noncompliance. A major provision of the Policy is the filing and annual updating of an Animal Welfare Assurance. The assurance document must fully describe the institution's animal care and use program. That program must comply with the Animal Welfare Act and other applicable federal laws and must adhere to the Guide for the Care and Use of Laboratory Animals (Guide). Like the AWA, the Policy requires each institution to establish an IACUC with at least one outside member representing the public. As described in the Policy, the duties and responsibilities of the IACUC are comparable to AWA requirements. Also, each application for a DHHS award includes the number and species of animals to be used, rationale for the use of animals, the veterinary care of the animals, description of the proposed use, procedures to minimize pain and discomfort and method of euthanasia. 4

The NIH Office for Laboratory Animal Welfare (OLAW) administers the Policy on behalf of the DHHS. OLAW is responsible for reviewing and approving institutional assurances, advising research facilities about compliance, evaluating allegations of noncompliance with the Policy and conducting site visits as needed. Guide for the Care and Use of Laboratory Animals The Guide vi is widely accepted by scientific institutions as a primary reference on animal care and use. First published in 1963, it has been revised six times, most recently in 1996. The purpose of the 118-page Guide is to assist institutions in caring for and using animals in ways judged to be scientifically, technically and humanely appropriate. The Guide was compiled by a panel of veterinary and other scientific experts brought together by the Institute of Laboratory Animal Resources (ILAR) of the National Academy of Sciences. Sections of the Guide cover recommended institutional policies (overall monitoring, veterinary care, and personnel qualifications, training and safety); animal environment, housing and management (cage size, behavioral management, food, water, bedding, sanitation and other issues); veterinary care (preventive medicine, surgery, pain, anesthesia, analgesia and euthanasia); and physical plant. Extensive references and a bibliography are provided. GOOD LABORATORY PRACTICE STANDARDS Both the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) enforce Good Laboratory Practice (GLP) rules. The FDA regulations (21C.F.R.58) vii apply to all projects yielding data to support new drug and medical device applications. EPA regulations (20C.F.R.160 and 20C.F.R.792) viii apply to all studies related to new pesticides or toxic substance approvals. The GLPs for both agencies address all areas of laboratory operations. Provisions relating to care and housing of test animals are identical in both GLP rules. Each has a full section on animal care, specifying Standard Operating Procedures (SOPs) for housing, feeding, handling and other conditions of care. Inspections are conducted by federal agency investigators, who visit each facility and are given access to all parts of the premises, all pertinent personnel and documentation. A final report and more detailed facility inspection reports are prepared after an audit is concluded. Noncompliance with GLPs can result in the federal agency s refusal to consider a study in support of an application; disqualification of the testing facility; or, in cases of alleged fraud, recommendation for criminal prosecution. OTHER FEDERAL AGENCY REQUIREMENTS Research conducted or supported by other federal departments is covered by policies that incorporate the Animal Welfare Act, Public Health Service requirements or both as appropriate. The Department of Defense (DOD) ix and the Veterans Administration (VA) x have directives and procedure manuals that explain compliance. The National Science Foundation xi relies upon the PHS Policy and assurance system, but also requires compliance with its own special requirements. 5

To protect humans working in research settings as well as research animals, the handling of infectious agents and similar biohazards must follow procedures established by the Centers for Disease Control and Prevention and U.S. Department of Labor. xii FREEDOM OF INFORMATION ACT The federal Freedom of Information Act (FOIA) xiii provides for public access to government information. A wide range of information about animal research and testing as well as its federal oversight is therefore available to the public through written or online requests. The public can obtain details about federally conducted or supported research projects, copies of PHS animal welfare assurance documents from awardee institutions, USDA annual reports filed by research facilities, and USDA, EPA and/or FDA inspection reports. i Interagency Research Animal Committee http://grants.nih.gov/grants/olaw/references/phspolicylabanimals.pdf. ii http://www.aphis.usda.gov/animal_welfare/awa.shtml iii http://www.aphis.usda.gov/animal_welfare/awr.shtml iv http://frwebgate.access.gpo.gov/cgibin/getdoc.cgi?dbname=browse_usc&docid=cite:+42usc289d v Office of Laboratory Animal Welfare, National Institutes of Health (revised August 2002) http://grants.nih.gov/grants/olaw/references/phspolicylabanimals.pdf. vi Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, Guide for the Care and Use of Laboratory Animals, (Washington, DC, National Academy Press, 1996). http://books.nap.edu/catalog/5140.html. vii http://www.nabrlaw.org/researchanimalprotection/usgovernment/foodanddrugadministra tionfda/goodlaboratorypracticeglp/tabid/692/default.aspx viii http://www.nabrlaw.org/researchanimalprotection/usgovernment/environmentalprotection AgencyEPA/EPAGoodLaboratoryPracticeStandards/tabid/694/Default.aspx ix The Care and Use of Animals in DOD Programs (2005) http://www.nabrlaw.org/researchanimalprotection/usgovernment/departmentofdefensedo D/tabid/724/Default.aspx x http://www.nabrlaw.org/tabid/726/default.aspx xi http://www.nabrlaw.org/tabid/681/default.aspx 6

xii Biosafety in Microbiological and Biomedical Laboratories (CDC-NIH 1999), http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm; Occupational Health and Safety in the Care and Use of Research Animals (NRC 1997) and Occupational Health and Safety in the Care and Use of Nonhuman Primates (NRC 2003) available through http://search.nap.edu/nap-cgi/de.cgi?term=occupational+health&x=14&y=7 xiii 5 U.S.C.552 http://www.usdoj.gov/oip/foiastat.htm 7