OLAW/USDA Regulations

The following was adapted, with permission, from: Essentials for Animal Research: A Primer for Research Personnel, Second Edition, B. Taylor Bennett, D.V.M., Ph.D.

INTRODUCTION

Since the ultimate responsibility for compliance with regulations that affect the care and use of animals lies with the investigator, it is important that he/she have a working knowledge of the basic regulatory requirements. In this manual, the types of regulations will be discussed under two broad general headings:

  1. Involuntary
  2. Voluntary

Involuntary regulations can be defined as those required by law or set forth as a condition of funding. There are four types of regulatory controls which can be considered as involuntary:

  1. The Animal Welfare Act (AWA)
  2. The Public Health Service Policy
  3. The Good Laboratory Practices Act
  4. The Requirements of Private Funding Agencies

Voluntary regulations can be defined as those that an individual or institution adheres to as part of their overall commitment to research and academic excellence. There are two types of regulatory controls which can be considered as voluntary:

  1. Accreditation by the American Association for Accreditation of Laboratory Animal Care (AAALAC)
  2. Requirements of Individual Users


INVOLUNTARY REGULATIONS

Animal Welfare Act
The Animal Welfare Act was first passed August 24, 1966, as PL-89-544. It was entitled the "Laboratory Animal Welfare Act" and authorized, "The Secretary of Agriculture to promulgate such rules and regulations, and orders as he may deem necessary to effectuate the purposes of this Act." The purposes of the original act were to:

  1. Protect the owners of dogs and cats from theft of such pets.
  2. Prevent the sale or use of dogs and cats which had been stolen.
  3. Insure that certain animals intended for use in research facilities were provided humane care and treatment.

In charging the Secretary, Congress specifically prohibited the promulgation of rules, regulations, or orders which would interfere with the conduct of actual research. Determination of what constituted actual research was left to the discretion of the research facility.

The original Act covered non-human primates, guinea pigs, hamsters, rabbits, dogs and cats. Humane treatment was required while they were at the dealers or research facility and while being transported by dealers. Dealers were required to be licensed. Research facilities which used, or intended to use, dogs or cats and either purchased them in commerce or received any federal funds were required to be registered.

The Secretary also established regulations and standards for the implementation of unannounced facility inspections and for the maintenance of specific records by dealers and research institutions. Responsibility for administering the Act was delegated within the United States Department of Agriculture (USDA) to the Administrator of the Animal and Plant Health Inspection Service (APHIS). Enforcement duties are the responsibility of the APHIS Deputy Administrator for Regulatory Enforcement and Animal Care (REAC). The actual inspections are conducted by 46 Veterinary Medical Officers working under one of the four REAC Sector Supervisors. The Sector offices are located in Fort Worth, Texas, Tampa, Florida, Annapolis, Maryland, and Sacramento, California.

In 1970 the original Act was amended (PL-91-579) and renamed the Animal Welfare Act. The amended Act covered broader classes of animals and included those used in exhibitions and sold at auction and regulated anyone involved in these activities. The definition of an animal was expanded to include all warmblooded animals. The definition of a research facility was expanded to include those institutions using covered live animals and not just dogs and cats. These facilities were required to file an annual report. Civil penalties were also added for refusing to obey a valid cease and desist order from the Secretary. The term "handling" was added to the basic categories for which standards were to be created and the phrase "adequate veterinary care" was broadened to include the appropriate use of anesthetics, analgesics and tranquilizers.

The intent of the original Act to prohibit interference with research was clarified and the Secretary was enjoined from directly or indirectly interfering with, or harassing in any manner, research facilities during the conduct of actual research or experimentation. The determination of when actual research was being done was still left to the discretion of the research facility itself.

In 1976, the Animal Welfare Act was further amended to enlarge and redefine the regulation of animals during transportation and to combat the use of animals for fighting. Essentially the Act was broadened to include all forms of commercial transportation of animals and required all carriers and intermediate handlers who were not required to be licensed under the Act to register with the USDA. It also expanded the definition of a dealer and extended the record keeping requirements to carriers and intermediate handlers.

In 1976, the Secretary also promulgated regulations which specifically excluded rats, mice, birds, horses and farm animals from the definition of an animal. This exclusionary language effectively excludes over 80 percent of the animals currently used in research, teaching and testing from coverage under the Animal Welfare Act.

In 1985 the Act was further amended with the passage of the Food Security Act of 1985 (PL-99-198) which contained an amendment entitled the "Improved Standards for Laboratory Animals Act." This amendment strengthened the standards for providing laboratory animal care, increased enforcement of the Act, provided for collection and dissemination of information to reduce unintended duplication of experiments using animals and mandated training for those who handle animals.

The 1985 amendment to the AWA also included development of standards: for the "exercise of dogs," for "provision of a physical environment which promotes the psychological well-being of primates," for limitation of multiple survival surgeries, and to require the investigator to consult with a veterinarian in the design of experiments which have the potential for causing pain to insure the proper use of anesthetics, analgesics and tranquilizers. Each research facility has to show upon inspection, and include in their annual report, assurances that professionally acceptable standards for the care, treatment and use of animals are being used during the actual research or experimentation. As part of these standards, the investigator is required to consider alternative techniques to those whichmight cause pain or distress in the experimental animals.

The 1985 amendment required the Chief Executive Officer of each research facility to appoint an Institutional Animal Committee consisting of at least three members including a doctor of veterinary medicine and one member who is not affiliated with the institution. The regulations promulgated to implement the amendment desig- nated this committee as the Institutional Animal Care and Use Committee (IACUC) and charged it to act as an agent of the research facility in assuring compliance with the Act. The Committee is required to inspect all animal facilities and study areas at least once every six months, and to review the condition of the animals and the practices involving pain to the animals to insure compliance with the regulations and standards promulgated under the Act. The Committee is also required to review once every six months the research facility's program to assure that the care and use of the animals conforms with the regulations and standards. The Committee must file a report of its inspection with the Institutional official of the research facility. If significant deficiencies or deviations are not corrected in accordance with the specific plan approved by the Committee, the USDA and any Federal funding agencies must be notified in writing.

The Committee must also review and approve all proposed activities involving the care and use of animals in research, testing or teaching procedures and all subsequent significant changes of ongoing activities. As part of this review, the Committee must evaluate procedures which minimize discomfort, distress and pain and that when an activity is likely to cause pain that a veterinarian has been consulted in planning for the administration of anesthetics, analgesics and tranquilizers and that paralytic agents are not employed except in the anesthetized animal. The IACUC must also determine that animals which experience severe or chronic pain are euthanatized consistent with the design of study, that the living conditions meet the species needs, that necessary medical care will be provided, that all procedures will be performed by qualified individuals, that survival surgery will be performed aseptically and that no animal will undergo more than one operative procedure that is not justified and approved. Methods of euthanasia must be consistent with the definition contained in the regulations.

The IACUC must also assure on behalf of the research facility that the principal investigator considered alternatives to painful procedures and that the work being proposed does not unnecessarily duplicate previous experiments. To provide assurance of the former the Committee must review the written narrative description provided by the investigator. This description must include the methods and sources used in determining that alternatives were not available. In reviewing proposed activities and modifications, the IACUC can grant exceptions to the regulations and standards, if they have been justified in writing by the principal investigator.

In addition to the above requirements, the research facility is required to provide training in the following areas to scientists, animal technicians and other personnel involved with animal care and treatment:

  1. Humane practice of animal maintenance and experimentation.
  2. Research or testing methods that minimize or eliminate the use of animals or limit pain or distress.
  3. Utilization of the information service of the National Agricultural Library.
  4. Methods whereby deficiencies in animal care and treatment should be re- ported.

The regulations require that each research facility establish a program of adequate veterinary care that includes: appropriate facilities, personnel and equipment; methods to control, diagnose and treat diseases; daily observation and provision of care; guidance to personnel on the use of anesthetic, analgesic and euthanasia procedures and pre- and post-procedural care. Specific requirements for maintaining records and filing annual reports are included in the regulations along with a miscellaneous section containing a variety of requirements to which a research facility mustadhere.

The most recent amendment to the AWA (PL 101-624) was passed in 1990 and was entitled the Pet Protection Act. The regulations developed to implement this amendment define the minimal holding period for animals in pounds and shelters that are sold to dealers, and establish record keeping requirements for dealers who obtain dogs or cats from these sources.

Public Health Service Policy
The Public Health Service Policy on Humane Care and Use of Laboratory Animals can be found in Chapter 4206 of the NIH Manual and Chapter 1-43 of the PHS Manual. The NIH originally initiated the Policy in 1971. It was extended to all PHS activities January 1, 1979, and was revised in the spring of 1985 with imple- mentation to be effective January 1, 1986. With the passage of the Health Re- search Extension Act of 1985 (PL-99-158), the Policy was further revised and the Director of the NIH was required by law to establish guidelines which heretofore had only been a matter of PHS policy. An additional revision was released in September 1986 which reflected the changes required by this Act.

Under the PHS policy, each institution using animals in PHS-sponsored projects must provide acceptable written assurance of its compliance with the Policy. In this Letter of Assurance the institutions must describe:

  1. The Institutional Program for the Care and Use of Animals.
  2. The Institutional Status.
  3. The Institutional Animal Care and Use Committee (IACUC).

The Institutional Program must include a list of every branch and major component, the lines of authority for administering the program; the qualifications, authority and responsibility of the veterinarian(s), the membership of the Institutional Animal Care and Use Committee and the procedures which they follow must be stated. The employee health program must be described for those who have frequent animal contact. A training or instruction program in the humane practices of animal care and use must be available to scientists, animal technicians and other personnel involved in animal care, treatment and use. The gross square footage, average daily census and annual usage of each animal facility must be listed. The Institutional Status must be stated as either Category one (1) (AAALAC accredited) or Category two (2) (nonaccredited). Institutions in Category two (2) must establish a reasonable plan with a specific timetable for correcting any departures from the recommendations in the Guide for the Care and Use of Laboratory Animals (86-23).

The IACUC must be appointed by the Chief Executive Officer and consist of at least five members; one of whom is a veterinarian with program responsibility, a practicing scientist, an individual whose expertise is in a non-biological science and an individual who is not affiliated with the institution. This Committee must use the Guide to review the animal facilities and the institutional program for humane care and use of animals at least once every six months and prepare reports of these evaluations for the responsible institutional official. The Committee must review and approve animal-related components of proposals and significant modifications made in ongoing activities involving the care and use of animals. The Committee is responsible for reviewing concerns involving the care and use of animals and making recommendations to the institutional official regarding any aspect of the animal program, the facilities, or the personnel training. They are also authorized to suspend activity involving the care and use of animals as set forth in the PHS Policy.

In reviewing the animal care and use component of a proposal, the IACUC must confirm that the project will be conducted in accordance with the AWA and consistent with the recommendations in the Guide. In addition, all procedures are reviewed to assure that pain or distress will be minimized and that (when necessary) appropriate anesthetics, analgesics and tranquilizers will be used. The living conditions and medical care available must be appropriate for the species used, and personnel conducting the procedures must be appropriately trained and qualified. Methods of euthanasia should be consistent with the recommendations of the American Veterinary Medical Association Panel on Euthanasia.

The investigator is responsible for completing a proposal in accordance with recommendations in the PHS Policy and the instructions contained in the PHS 398 application packet. As of September 1991, the instructions for completing 398 can be found in two locations within the application package. On page 13 the research investigator's responsibilities for assuring compliance with the PHS Policy are clearly addressed. Detailed instructions for completing Section 6 of the Research Plan which describes the use of Vertebrate Animals can be found on page 23.

The institution is responsible for maintaining all the necessary records to document compliance with the PHS Policy and for filing annual reports developed by the IACUC which detail any changes in the program and indicate the dates of the semi-annual inspections and programmatic reviews.

The PHS Policy described above is intended to implement and supplement the "U.S. Government Principles for the Utilization and Care of Vertebrate Animals in Testing, Research and Training." The nine principles are published in the PHS Policy and in the Appendix of the Guide. All those responsible for the design, supervision and review of the animal care and use component of a proposal should be familiar with this document.

Good Laboratory Practices
In 1978 the Food and Drug Administration adopted the Good Laboratory Practices rules which applied to all regulated parties who conduct nonclinical safety assessment studies. The rules require the creation of Standard Operating Procedures for all aspects of the study including animal care and use. A Quality Assurance Unit must be established to conduct internal inspection of practices and records to insure compliance with established policies and procedures. In general the recommendations contained in the Guide would suffice in terms of animal care when adherence is properly documented.

Private Funding Agencies
In recent years the requirements of many private funding agencies which fundresearch projects involving the care and use of laboratory animals havechanged. It is important to obtain the requirements from the agency before spending time preparing a proposal. Some of these agencies not only require review of the proposal by the IACUC, but require proof of accreditation by AAALAC. In many in- stances, the proposals must be reviewed and approved prior to submission.

VOLUNTARY REGULATIONS

American Association for Accreditation of Laboratory Animal Care (AAALAC)
AAALAC was originally chartered April 30, 1965, as a voluntary organization that accredited institutional programs of animal care and use. AAALAC is governed by a Board of Trustees composed of representatives of 39 professional organizations. An 18-member Board-appointed Council on Accreditation along with four scientific/technical panelist make recommendations based on the results of site visits to evaluate an institution's compliance with the recommendations contained in the Guide. This is a peer review process in which standards are being continually upgraded to reflect current knowledge in laboratory animal medicine and science. In its accreditation program the AAALAC Council uses the Guide more as a compilation of regulatory "standards" and not as a set of "recommendations." Since the AAALAC accreditation program and the Guide are so closely linked, a brief review of the Guide's history and its current contents are warranted. In 1963 the first Guide for Laboratory Animal Facilities and Care was published by the Institute for Laboratory Animal Resources (ILAR) under a contract from NIH. Since its original release the Guide has been revised in 1965, 1968, 1972 (when the title was changed to the Guide for the Care and Use of Laboratory Animals) 1978 and 1985. In the most recent revision, the organization of the chapters was changed to reflect the increasing role and responsibility of the institutional program in establishing acceptable standards for the care and use of laboratory animals. The first chapter is now Institutional Policies. The remaining four chapters are Laboratory Animal Husbandry, Veterinary Care, Physical Plant and Special Considerations.

Prior to an AAALAC site visit, each institution is required to prepare a description of the institutional facilities and programs using the AAALAC Outline for Description of The Institutional Animal Care and Use Program, which follows the Guide's chapter headings.

Once accredited, an institution must submit an annual report describing changes in the program and facilities and documenting the annual usage of animals. Site visits occur at least every three years and these visits consist of an inspection and review of policies, procedures and facilities which comprise the animal care and use program inclusive of selected animal usage areas. Should deficiencies be identified in a previously accredited program, the institution is either granted a definied period in which to make specified changes, or if the deficiencies are major, accreditation could be withdrawn.

Individual Users
The instructions for completing PHS 398 clearly define the roles and responsibilities of the investigator in assuring proper care and usage of laboratory animals. In addition to this requirement, it should be understood that any type of care or use of an animal which results in the creation of nonexperimental variables can potentially compromise the integrity of an entire project. As part of their commitment to scientific excellence, the users should provide the impetus for setting and maintaining high standards for the care and use of laboratory animals within their individual and collective institutions. Failure to do so invites increased internal and external regulatory requirements which can drain limited institutional research resources. Good animal care is good science; the practice of good science should be the primary goal of all who have chosen careers in the scientific community.

Summary
In summary, the regulations that affect the use of animals in research, teaching and testing programs are numerous. A working knowledge of the applicable regulations is necessary if the principal investigator is to insure that proposals for funding contain the necessary information and to assure that the conduct of all research proposals is in compliance with the requirements of the regulatory and funding agencies. While the ultimate responsibility for compliance rests with the principal investigator, institutional policies should be designed to provide those responsible for compliance with the necessary resources to do so.

References
Application for Public Health Service Grant, PHS, 398. Revised September, 1991. OMB No. 0925-001.
Animal Welfare Act (Title 7 U.S.C. 2131-2156), as amended by PL-99-198, December 12, 1986.
Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23.
Public Health Service Policy on Humane Care and Use of Laboratory Animals. Revised as of September 1986.
Non-Clinical Laboratory Studies. Good Laboratory Practice Regulations. Register, December 22, 1978, Part II, pp. 59986-60026.Public Law 99-198. Code of Federal Regulations, Title 9, subchapter A, Animal Welfare 1989.
Townes, J. Federal Regulations an Overview, Lab Animal, July-August 1980; 9:4 l6-22.