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Regulatory Requirements Regarding Use of Laboratory Animals

By

Michael J. Huerkamp

, DVM, Emory University

Last full review/revision Feb 2021 | Content last modified Feb 2021

Most American laboratories must adhere to two main sets of animal welfare regulations: the Animal Welfare Act (AWA; Public Law (PL) 89-544 of 1966), with the associated Animal Welfare Act Regulations (AWAR) defining standards and requirements, and the Health Research Extension Act of 1985 (PL 99-158), which provides the legislative mandate for the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy).

The Animal and Plant Health Inspection Service (APHIS) of the USDA oversees enforcement of the AWA, which covers the care of research animals and includes guidelines for the oversight and conduct of studies intended to minimize or prevent pain or distress of laboratory animals. The AWA also regulates zoos, exhibitors, animal dealers, and those who transport animals in commerce. All warm-blooded species are regulated by the AWA, whether alive or dead, except for domestic mice and rats bred for scientific purposes, birds, and farm animals used in agricultural research. Provisions for veterinary care have existed under the AWA since 1970; in 1985, requirements were added for exercise for dogs and ensuring the psychological well-being of nonhuman primates. AWA enforcement is through a self-reporting mechanism along with routine, unannounced inspections by APHIS. Failure to meet the requirements of the AWA can result in fines, citations, criminal proceedings, or revoked registration with disqualification to use AWA-regulated species in research.

The PHS Policy relies on the Guide for the Care and Use of Laboratory Animals ("The Guide"), a set of research animal care standards first issued in 1963. The PHS Policy requires institutions to use this guide as a basis for developing and implementing institutional programs for research involving animals. The PHS Policy has been modified only once, in 2002, while the Guide, now in its 8th edition, was last revised in 2011. The policy applies to all research institutions awarded federal grants—in excess of $27B in 2018 from the National Institutes of Health alone. It covers all vertebrate animals, not just those that are warm-blooded. Regulatory compliance is based on a system of self-regulation whereby institutions must provide to federal officials: a written Animal Welfare Assurance that describes their compliance with the PHS Policy, updates via an annual report, timely reporting of deficiencies, and site visits for-cause or other purposes. Failure to adhere to PHS Policy can result in revocation of federal funding for some or all research projects at the institution.

The 220-page Guide is organized into 5 chapters, covering these subject areas:

  • key defining concepts, including applicability, a brief review of the ethical principles in the humane care and use of animals in research, and clarifying definitions

  • articulation of the basics of an animal care and use program, most prominently oversight structure, all aspects of safety, and requirements for research and animal care training

  • the environment, housing, and management of research animals

  • veterinary care

  • animal research facility design and physical plant operation

Within the context of the Guide, the attending veterinarian (AV) was conferred unquestionable responsibility for the welfare of any animal in research, including at all times during experimentation, in all phases of its life, and with the authority to prescribe treatment or require euthanasia.

Program Accreditation for Animal Research Programs

 AAALAC International, incorporated in 1965 and headquartered in Frederick, MD, is a private, nonprofit organization that promotes the humane treatment of animals in the valid conduct of science through voluntary accreditation and assessment programs. More than 1,000 companies, universities, hospitals, government agencies, and other research institutions in 47 countries have voluntarily earned AAALAC accreditation. as of 2019. Institutions that seek AAALAC accreditation are subject to comprehensive peer review of their animal care and use program every 3 years; this accreditation is credited by the National Institutes of Health as a means of demonstrating compliance with PHS Policy.

Veterinary Care of Laboratory Animals

The obligations of the AV and the requirements of the associated program of veterinary care were derived from a blend of sources, most prominently the AWAR and The Guide. Under provisions of the AWAR, everyone who uses animals in research, exhibits them, sells them at the wholesale level, or transports them in commerce must have an established program of veterinary care (PVC) and animal husbandry. APHIS requires the owner of each licensed and registered facility to define a written PVC, including the full- or part-time employment of an AV.

The AV is responsible for the well-being and clinical care of all animals used in research, testing, teaching, and production at all times and during all phases of life. The AV also has the authority to treat, remove from experiment, and take appropriate measures to relieve severe pain or distress, including euthanasia, for any animal. A key requisite for this is for the AV to balance the goals of the experiment with knowledge of the research animal model systems in use, including their manifestations and experimental complications. In cases where the AV is not a full-time employee, the PVC must detail the scheduled frequency of visits by the AV, the channels of communication with the AV, and address how veterinary services are otherwise available at all times. The AV is then responsible for reviewing the facility’s PVC at least once a year to ensure that it remains in conformance with the standards of veterinary care for each species.

Whatever the employment arrangement, the veterinarian must have sufficient authority to ensure adequate veterinary care across the expanse of facilities, personnel, equipment, and services to satisfy a broad array of requirements. These include, but are not limited to: legal procurement; acclimation and quarantine; proper housing, husbandry, nutrition, and provisions for exercise; daily health checks and reporting; disease and injury prevention, surveillance, and response; nutrition; emergency care; safe and appropriate use of pesticides; and, for wild or exotic animals, capture and restraint methods. 

Jointly with the Institutional Animal Care and Use Committee (IACUC, see below), the AV is responsible for overseeing surgery programs and assuring that surgeons creating animal models are suitably qualified and trained in the procedures, including aseptic technique. With the IACUC, as well, the AV contributes expertise in defining the optimal conditions of social and environmental enrichment for each species maintained. Likewise, the veterinarian provides guidance and participates in the training of personnel who care for or use animals, including handling, immobilization, anesthesia, sedation, tranquilization, pain management, pre- and post-procedural care, and euthanasia.

Institutional Laboratory Animal Care and Use Committee

The IACUC, as authorized and guided by the AWA and PHS Policy, oversees all aspects of the care and use of animals in research and serves as a critical instrument in safeguarding the public trust. According to the AWA, the IACUC must consist of at least one veterinarian with training in laboratory animal science and expertise with the species used in experiments, at least one practicing research scientist, and at least one person not affiliated in any way with the institution. The PHS Policy adds a nonscientist to the list and increases the minimum to five voting members. Because the regulations and associated guidance exist on a general basis and allow for professional judgment, IACUCs have a critical responsibility in their interpretation and evaluation. For these reasons as well as the realities of the large scale and complexity of some institutions, the IACUC in many cases numbers far greater than those minimums and not uncommonly broadens expertise into many different scientific disciplines and areas such as ethics, jurisprudence, library science, biostatistics, and safety.

Each IACUC has three main areas of responsibility: review of research protocols; regular evaluations of the institution’s animal care and use, which includes applicable programs (eg, veterinary care) and semi-annual inspections of animal housing areas and surgeries; and judicature. The latter includes investigating animal welfare concerns, addressing unacceptable protocol deviations, and adjudication (eg, where protocols may be ambiguous and the AV and scientist have different interpretations). The Institutional Official, the person with institutional authority and means to assure the effectiveness of the IACUC, receives reports of these activities.

Review of research protocols by the IACUC involves considering the merits of the animal study in the context of a broad range of complex scientific, animal welfare, and veterinary topics. Assessment includes evaluating the likelihood of the generation of knowledge or improvements in human and/or animal well-being that exceeds in beneficial value anything untoward experienced by the animal subjects. The AWA requires, in the process of protocol preparation, that scientists consult with a veterinarian in cases where the subjects may experience more than momentary or slight pain or distress. Protocols may be reviewed by a quorum of the IACUC at a convened meeting, which is termed full committee review, or by delegation to a subset of IACUC members outside of a meeting, defined as designated member review.

Protocols expire at three years and, if continued, are renewed as a de novo creation. Within the triennial period, protocols are modified with review by means of full committee review, designated member review, or by veterinary verification and consultation. The latter allows for the IACUC by a defined policy to entrust review of certain, minor changes to a qualified veterinarian such as those related to anesthesia, euthanasia methods, and therapeutic drugs.

The IACUC also has the responsibility to monitor the compliance of ongoing studies and the authority to suspend research that is not done in accordance with the conditions of approval or with unforeseen negative consequences.

Emergency Preparedness for Animal Research Programs

History shows that the enormous national investment in animals, equipment, experiments, and animal research facility structures themselves are regularly and often unpredictably subject to the effects of natural events, man-made disasters, or failures of technology. The Guide requires that each institution craft a comprehensive emergency operations and disaster responsiveness plan to promote resilience and prevent, absorb, recover from, and adapt to adverse events. Such written plans are required to include contingencies to evacuate or depopulate the full census of laboratory animals.

Although the plan is a living document, subject to continued evaluation and revision as vulnerability to various hazards changes, it is only one component in the cycle of preparation, mitigation, response, and recovery in association with disasters and emergencies. Structural and program resilience begins with design and hardened construction incorporating failsafe mechanisms and redundancy (eg, emergency power) and continues with preventive maintenance and worksite and personal preparedness, including drills and tabletop exercises. The most successful approach is to focus on coping with interruptions in function, most commonly utility and/or personnel shortages. In protection of these knowledge and economic hubs, the plan specific to the animal research program should be integrated into the larger one of the parent institution and then linked with private and public community partners and stakeholders up to the federal level.

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