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Unit Two – Laws, Regulations, and Policies Affecting the Care and Use of Animals in Research

Here we look at the regulations affecting use of animals in research, and
consider the responsibilities of the institution, animal care and use
committee, research staff, and veterinarian.

 

Acknowledgement

Much of this unit is adapted from the author’s minilesson on “How to Work with Your Institutional Animal Care and Use Committee,” part of the Contemporary Values in Science and Society web site.

Before you proceed to the reading assignment or the rest of this Unit, here is another survey question:

Do you think laws protecting animals from inhumane treatment in teaching and research:

• Go too far
• Don’t go far enough
• Are OK now
• Don’t know?

Readings:

OLAW offers “a tutorial for new animal care and use committee members, institutional administrators, investigators, animal care personnel, veterinarians, or others who are interested in learning about the PHS Policy.” The tutorial is quite extensive, but the "Introduction" and "Relevant Documents" provide good background for this Unit.


Many researchers believe that the existing regulations go too far, not because they want freedom to treat animals poorly, but because they feel there is an excessive amount of required paperwork that doesn’t benefit the animals. Initial examination of the forms required before a study can begin may support that view. (See, for example, the Sample Protocol Form suggested by the Office for Laboratory Animal Welfare. ) In this unit, you will gain an appreciation for why so many questions are asked of a researcher before starting work with animals.

Many people believe that existing laws don’t go far enough, in part because of a few well-publicized incidents of apparent misuse of animals in research (primarily in the 1980s), combined with a persistent, vocal campaign by animal rights activists/organizations to stop all use of animals in research. Our veterinary student respondents also have concerns about the adequacy of regulations (roughly 30% indicating that current laws don’t go far enough), although it’s not clear that his judgment is based on firm knowledge of current regulations; 30-40% admitted that they really don’t know.

 

Administrative Ethics

We introduced this concept in Unit 1: administrative ethics are the actual rules and regulations of governmental bodies. In this unit we will concentrate on federal regulations, but there also may be regulations at the state and local level and, equally important, rules at the institutional level. Furthermore, there are a variety of policies, standards, and guidelines that go along with the actual rules and regulations.

Before we get into more specific rules for working with animals in research, look at the U.S. Government Principles for the Utilization and Care of Animals Used in Research, Teaching and Testing. These nine principles articulate for all government agencies the ethical standards for how animals should be treated.

 

Discussion Question

After studying the U.S. Government Principles, how well do you think they articulate the standards for how animals ought to be used in research? Do the principles convey an appropriate societal ethic for animal use? Are there principles that should be changed or amended?

 


The Rules

In the U.S., two key federal laws governing the use of animals in research were passed in 1985: the Health Research Extension Act (HREA) and key amendments to the Animal Welfare Act (AWA). Laws, as passed by congress, provide broad directives, including designation of a responsible federal agency. That agency is then responsible for creation of the regulations and associated policies. For the AWA, responsibility lies with the U.S. Department of Agriculture, Animal and Plant Health Inspection Service, Animal Care; the rules promulgated by USDA Animal Care are commonly referred to as the AWA regulations (AWARs). In the case of the HREA, responsibility lies with the Office of Laboratory Animal Welfare (OLAW) in the Department of Health and Human Services, and the rules are articulated in the “Public Health Service Policy for the Humane Care and Use of Laboratory Animals” (PHS Policy).

Although many details of the two sets of regulations are similar, there are differences. The AWA covers (almost) all research facilities, but applies only to “animals,” as defined. This definition specifically excludes laboratory rats and mice, birds, and livestock species used in agricultural research. The PHS Policy covers all vertebrates, but applies only to projects funded by PHS agencies such as the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control. These differences, as well as the fact that some institutions using animals are not covered by either set of regulations, mean that the institution itself must set policy about the animal care and use program. Many, if not most, institutions have judged that a coherent policy requires applicability to all animals regardless of funding source. (See, e.g., the North Carolina State University policy.)

At the heart of the federal regulations are requirements for an Institutional Animal Care and Use Committee (IACUC). Many institutions had for some time utilized committees to assist in the oversight of the animal care and use program. However, it wasn’t until 1985 that legislation was passed requiring an IACUC; the designated responsibilities are similar in the two laws (see text-block).

Federally-Mandated Functions of the IACUC

• Review at least once every six months the institution's program for humane care and use of animals.
• Inspect at least once every six months all of the institution's animal facilities.
• Prepare reports of the IACUC evaluations and submit the reports to the Institutional Official. The reports must distinguish significant deficiencies from minor deficiencies. If program or facility deficiencies are noted, the reports must contain a reasonable and specific plan and schedule for correcting each deficiency.
• Review concerns involving the care and use of animals at the institution.
• Make recommendations to the Institutional Official regarding any aspect of the institution's animal program, facilities, or personnel training.
• Review and approve, require modifications in (to secure approval) or withhold approval of activities related to the care and use of animals.
• Review and approve, require modifications in (to secure approval), or withhold approval of proposed significant changes regarding the use of animals in ongoing activities.
• Be authorized to suspend an activity involving animals.

 

The federal regulations differ slightly in the requirements for the composition of the IACUC. The AWARs state that:

The Committee shall be composed of a Chairman and at least two additional members; of the members of the Committee:

• At least one shall be a Doctor of Veterinary Medicine, with training or experience in laboratory animal science and medicine, who has direct or delegated program responsibility for activities involving animals at the research facility;
• At least one shall not be affiliated in any way with the facility other than as a member of the Committee, and shall not be a member of the immediate family of a person who is affiliated with the facility. The Secretary intends that such person will provide representation for general community interests in the proper care and treatment of animals.

The PHS Policy requires at least five members and, in addition to the above:

• one practicing scientist experienced in research involving animals; and
• one member whose primary concerns are in a nonscientific area (for example, ethicist, lawyer, member of the clergy).

Institutions use a variety of standards documents and guidelines, in addition to the U.S. Government Principles (above), to assist in their evaluation of animal care and use:

• The AWARs specify responsibilities of the IACUC, but also include regulations for the registration of research facilities, personnel qualifications and training, and the provision of veterinary care. There are detailed husbandry standards that must be followed for the species covered, including minimum standards for indoor and outdoor facilities, husbandry and sanitation, feeding and watering, space requirements, heating and ventilation, transportation, etc.
• The PHS Policy refers to the AWARs, but also specifically to the Guide for the Care and Use of Laboratory Animals, a publication of the Institute for Laboratory Animal Research. The Guide contains chapters that address institutional policies and responsibilities; animal environment, housing and management; veterinary medical care; and the physical plant.
• Another important publication is the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching, published by the Federation of Animal Science Societies. This document does not have a direct regulatory connection, but is widely used by institutions, and AAALAC (below), in evaluating animal care and use programs in the agricultural setting.
• One of the U.S. Government Principles refers to appropriate euthanasia of laboratory animals. Comprehensive guidelines for euthanasia methods are in the Report of the American Veterinary Medical Association Panel on Euthanasia.
• There are a variety of other useful resources for researchers, the institution, and IACUCs to use to better assure the humane care and use of animals in various research settings. Examples include professional guidelines for field research (birds, fish, mammals), and use of mammals in neuroscience research. An excellent list is on the OLAW web site.

In addition to the rules, many institutions have judged it important to demonstrate a higher level of accountability by seeking voluntary accreditation by the Association for the Assessment and Accreditation of Laboratory Animal Care – International (AAALAC). This nonprofit organization now accredits more than 650 companies, universities, hospitals, government agencies and other research institutions throughout the world.

 

Study Questions

1. Most research institutions have animal use activities that fall under at least one of the two federal regulations discussed above. What is an example of an institution or situation in which the animal use is not specifically covered by either of the regulations?

2. Read the AWAR sections on dogs and nonhuman primates. What unique requirements are written for these species?

3. What is the Animal Welfare Assurance required as part of the PHS Policy?

 

Discussion Questions

1. Why does the federal government have two sets of regulations governing the welfare of animals used in research, teaching and testing? Can you think of an advantage of this arrangement?

2. IACUCs are often criticized by animal rights activists for under-interpretation of the regulations and generally inadequate oversight. Why might the regulations, as written, cause some suspicion along these lines?

3. What do you think the purpose is of the unaffiliated IACUC member? From both the institutional and community perspective, what type of person would make a good unaffiliated member?

 

Protocol Review

A key responsibility of the IACUC is that animal use activities must be reviewed and approved by the IACUC before a project can begin. It is therefore important that research staff understand the process in their institution, including the timeline and deadlines for protocol review. There usually are institution-specific instructions available for completion of the protocol-review process, and consultation is typically available from an IACUC office as well as IACUC members. There often is a mechanism for “pre-review” of protocols before distribution of a final draft to committee members. Veterinary staff are also available for consultation, and should be contacted if projects involve potential for pain or distress.

The regulations do not require that all protocols be discussed at a convened IACUC meeting, but some institutions have judged it important to do so. More commonly, the IACUC assigns a “designated reviewer” to conduct the review. However, the regulations specify that there must be opportunity for every IACUC member to request discussion of a protocol at a convened committee meeting.

Any significant change in an approved animal use activity must be reviewed and approved by the IACUC. This typically is handled through an amendment or addendum process with institution-specific paperwork. As with initial review, there must be opportunity for every member to request discussion at a convened committee meeting. A recent notice from NIH clarifies the specific issue of whether personnel changes are “significant,” and includes links to information on other significant changes.

Regulations require “continuing review” of all approved animal use activities. The AWARs require annual review; lack of details in the regulations means that there may be significant differences among institutions in how this is handled. The PHS Policy requires “de novo” review of animal use activities every three years, and this usually means submission of new paperwork.

In addition to issues directly related to the protocol review process, there may be institutional requirements for training, facility orientation and security measures, and enrollment in an occupational health and safety program. Many institutions link these requirements to the protocol review process.

 

Difficult Issues in Protocol Review – Potential for Pain and Distress

Minimizing pain and distress, consistent with meeting experimental objectives, is a key feature of the regulations and IACUC/institutional responsibility; Unit Three addresses this important area in greater detail. The IACUC will need to know what the potential is for pain or distress associated with experimental manipulations, including clinical and behavioral abnormalities associated with spontaneous or induced animal models (e.g., mutant and transgenic mouse strains).

By regulation, veterinary staff must be consulted in the planning of studies involving potential pain or distress; planning may involve both the preparation of the protocol for IACUC submission and training in the experimental methods. Veterinary consultation is valuable for understanding:

• regimens for use of anesthetics, analgesics, and tranquilizers, including monitoring;
• how to recognize species-specific signs of pain and distress;
• surgical approaches and aseptic technique;
• post-procedural monitoring and intensive care.

Regulations also require that the PI consider alternatives to potentially painful or distressful procedures. The IACUC, through the protocol review process, must determine that this has been done appropriately. Alternatives are taken to mean not just replacement of animals with non-animal methods, such as computer simulations, but also reduction of animal numbers to the minimum necessary to satisfy experimental objectives, and refinement of methods to minimize pain and distress (the so-called 3 Rs). Current regulatory expectations are that, in most cases, the Principal Investigator (PI) perform a literature search for alternatives. Unfortunately, when done properly, this can be a time-consuming process. The Animal Welfare Information Center was created as part of the 1985 amendments to the AWA, and provides assistance to researchers in the search for alternatives.

One of the hardest jobs for both research staff and the IACUC is discussion and evaluation of methods to minimize pain and distress. This involves an inevitable balancing act, or cost-benefit analysis, between the experimental objectives and animal welfare. When there is potential for pain or distress, researchers are expected to carefully monitor animals and relieve the pain or distress whenever possible. One method to accomplish this is by administration of anesthetics or analgesics. By regulation, a specific scientific justification must be provided whenever anesthetics or analgesics are withheld in painful conditions; this might be necessary when the drugs would interfere with the interpretation of experimental data. Pain and distress also can be reduced by euthanizing the animal, and defining so-called humane endpoints (e.g., limits on size of tumors in cancer studies) is an important part of protocol preparation and review.

The AWARs require that research facilities file an annual report that accounts for numbers of animals used, by species and category of pain or distress. Many IACUCs require that this information be provided in the protocol form, and the IACUC may provide additional guidelines for determining the appropriate category.

 

Difficult Issues in Protocol Review – Justification for using animals, species, and numbers used

U.S. Government Principle II states that procedures using 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.” Protocol forms typically have a question that asks about the purpose and importance of the work, and PIs should use this as an opportunity to provide basic background information so IACUC members can understand why the animal use activity is needed.

Regulations also require that the PI provide a justification for using animals, and for the specific species and numbers of animals to be used. These are sometimes difficult issues to address, but involve basic questions that should be considered in the planning of any experiment using animals. Implicit in these questions is the notion that animals should not be wasted. The Animal Welfare Information Center has useful information and web links to assist with statistical considerations and animal numbers.

 

Difficult Issues in Protocol Review – Personnel qualifications and training (more below)

The IACUC must determine that personnel working with animals are adequately qualified to perform the procedures described in the protocol; this includes everything from basic animal handling to anesthesia support and surgery to euthanasia. Thorough training of personnel is one of the most important refinements that can be made in studies using animals. Some institutions, especially in industry, require detailed training records to document individual qualifications. However, many IACUCs rely on descriptions of qualifications provided in the protocol form.

 

Study Questions

1. Do the regulations include provision for expedited review of protocols, i.e., a mechanism to speed the approval process for small pilot studies or other potential extenuating circumstances? What key feature of the regulations must be included in the review process for any new protocol or significant change to an existing protocol?

2. Under the PHS Policy, protocols may be approved for up to three years. Do the regulations include provision for extending that approval period (e.g., granting a grace period) without additional IACUC review?

 

Discussion Questions

1. The USDA has stated that, for the purposes of both the search for alternatives and in reporting, surgical procedures are considered potentially painful. Assuming that appropriate anesthesia is used, does this seem a correct interpretation?

2. Should all protocols be reviewed at a convened committee meeting? Should institutions specify certain types of protocol that will be discussed at a meeting? What are the advantages (and disadvantages) to either of these approaches?

3. As an IACUC member, what types of information would you want to see in order to assess a person’s qualifications for conducting an animal study?

 

Suspension of an Activity

The IACUC has the authority, at a convened meeting, to suspend an activity (protocol) it has previously approved. This, like withholding approval of a new protocol, is an uncommon event, and one that both the IACUC and research staff would prefer to avoid. Suspension of an activity is a matter of ensuring institutional compliance; it usually is done when the committee learns that a researcher is conducting an animal-use activity without prior approvals. While it may be difficult, especially in a large/busy research laboratory, to keep up with all the activities, it remains the PI’s responsibility to notify the committee whenever there is a significant change in the work (see above). This includes not only changes in direction and addition of new studies, but also reporting any unexpected results that might affect animal welfare.

 

Personnel Qualifications and Training

Although there are specific requirements for IACUC consideration of personnel qualifications (see above), the responsibility for ensuring that personnel are adequately qualified to work with animals rests with the institution. There is wide variability in how institutions accomplish this. There may be a series of seminars or workshops for research staff, and/or on-line instructional materials; attendance or completion of a course may or may not be mandatory. There is no regulatory requirement that personnel pass a test, but many institutions include an examination and/or some type of certification of course completion. The AWARs specify that training must be available in certain areas (see text-block), but probably most institutions have judged that some level of training is required before an individual can use animals; some may require follow-up refresher courses or re-certification. Research staff should review their institution’s policies in order to avoid delays in beginning a project.

Personnel Training Components
(from the AWARs)


Training and instruction of personnel must include guidance in at least the following areas:

• 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;
• The concept, availability, and use of research or testing methods that limit the use of animals or minimize animal distress;
• Proper use of anesthetics, analgesics, and tranquilizers for any species of animals used by the facility;
• Methods whereby deficiencies in animal care and treatment are reported, including deficiencies in animal care and treatment reported by any employee of the facility. No facility employee, Committee member, or laboratory personnel shall be discriminated against or be subject to any reprisal for reporting violations of any regulation or standards under the Act;
• 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 Act.

 

Semiannual Inspection of Facilities and Evaluation of Programs

The IACUC must inspect all animal-housing facilities, and evaluate animal care and use programs, at least every six months. “Programs” in this sense are taken to mean: the institutional policies and procedures for how the IACUC is administered, including filing of reports and record keeping; the program for ensuring that personnel working with animals are properly trained and qualified; the program of veterinary care; and the occupational health and safety program for personnel working with animals. OLAW provides assistance to IACUCs in understanding the expectations for program review as part of its tutorial on the PHS Policy , including an optional, sample checklist.

The IACUC must prepare a report of its findings and submit that report to the Institutional Official (IO). (The IO is a designated official who has the authority, on behalf of the institution, to ensure compliance with relevant regulations and policies for the appropriate care and use of animals.) The semiannual report must distinguish significant from minor deficiencies found in review of facilities and programs, and provide a reasonable and specific plan for correction of deficiencies identified.

Semiannual inspection of facilities applies to all animal housing areas, but also to other places where animals are used in research. Current interpretation from federal agencies is that this schedule should include places where there is survival surgery. Investigator laboratories in which animals are used also must be inspected, although frequency of inspection should depend on nature of animal use in that area. The IACUC remains responsible for all areas where animals are used.

 

Study Question

Based on the regulations, what standards are used by the IACUC in conducting its semiannual review of facilities and programs?

 

Discussion Question

There is no regulation to guide IACUCs on whether inspections should be announced (scheduled in advance with the facility manager or laboratory supervisor) or unannounced. What are some arguments for each approach?

 

Review of Concerns

A specific responsibility of the IACUC is to review and investigate any concerns related to animal care and use. Concerns may come from public complaints, or from within the institution. This regulation has several implications for research staff. First of all, it is a mechanism to voice an animal welfare concern that they may witness, e.g., improper care or treatment of animals by animal care staff or other researchers. Second, a concern could be brought against a researcher, e.g., improper handling of one of their animals. Finally, all staff should be aware that so-called whistle blower protections are required by the AWARs. This means that someone who brings a concern to the IACUC may be legally protected against discrimination or reprisal.

There are other mechanisms for individuals to express concerns about how animals are cared for or used, and personnel are encouraged to use these avenues first (e.g., contacting supervisory, management or veterinary staff in the animal care unit). Research staff should be familiar with their institution’s key personnel involved with animal care, as well as the specific mechanism to bring concerns to the IACUC.

 

Discussion Questions

1. Do you think the IACUC should act on anonymous complaints about improper animal care or use?

2. How should the IACUC go about conducting an investigation of an animal welfare concern?

 

Veterinary Care

The AWARs, Guide for the Care and Use of Laboratory Animals and the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching all highlight the importance of a veterinary care program and the role of an attending veterinarian. The institutional attending veterinarian is responsible for ensuring provision of a comprehensive program of veterinary medical care for all animal colonies. This responsibility is executed by a combination of directly supervised veterinary care in some units and oversight of health care support by others. A useful standard for the veterinary care program is the position paper “Adequate Veterinary Care” by the American College of Laboratory Animal Medicine.

Components of a veterinary care program include the following:

• Appropriate facilities, personnel, equipment, and services to provide adequate veterinary care
• A program of veterinary care that addresses:

- Preventive medicine
- Surveillance, diagnosis, treatment, and control of disease, including zoonosis control
- Management of protocol-associated disease, disability, or other sequelae
- Anesthesia and analgesia
- Surgery and postsurgical care
- Assessment of animal well-being
- Euthanasia

• Daily observation of all animals by personnel trained to assess the animals' health and well-being
• Mechanism for direct, frequent, and regular communication among the personnel responsible for daily animal care and observation, the principal scientist, and the unit attending veterinarian
• Availability of emergency, weekend, and holiday care for animals
• System of medical record keeping consistent with regulations, standards, and institutional policy
• Provisions for adequate preprocedural and postprocedural care in accordance with established veterinary medical and nursing procedures
• Guidance and training of personnel who care for animals regarding handling, immobilization, anesthesia, analgesia, tranquilization, and euthanasia
• Advice 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 and techniques proposed or in use.

Study Questions

1. What are the required qualifications for an attending veterinarian?

2. Must a veterinarian be involved in all aspects of animal observation and treatment?

 

Discussion Question

Under what circumstances should a veterinarian be expected to directly evaluate an animal health abnormality? Are there situations where a veterinarian need not be called for a sick animal?

 

Occupational Health and Safety

According to both the Guide for the Care and Use of Laboratory Animals and the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching, institutions must provide an occupational health program for personnel who work with animals. The discussion in the Guide provides an overview of program components, but also refers to a more comprehensive NRC document, Occupational Health and Safety in the Care and Use of Research Animals.

Coordination and administration of this program is typically the responsibility of the institution’s health and safety office, but the IACUC is responsible for evaluating adequacy of the program as part of its required semiannual evaluation of facilities and programs. There is substantial flexibility in the regulations with respect to details of the occupational health program and, accordingly, wide variation in institutional requirements. (As an example, click here to see a description of the program for North Carolina State University.) As with the personnel training program, the institution may link final protocol approval to enrollment in the occupational health program.

 

Study Questions

1. Based on discussion in the Guide, what institutional components (individuals or offices) should be involved in the planning and execution of an occupational health program?

2. Why is individual medical assessment an important component of an occupational health program?

 

Institutional Responsibilities

Current regulations and standards refer to institutional responsibilities, but it is the people within an institution who carry responsibility for appropriate animal care and use. That responsibility is divided among multiple levels, from the Chief Executive Officer to the individual PI and his/her research staff, and including the Institutional Official, Attending Veterinarian, and IACUC. “Guidelines for Governance and Management of Animal Resources” is a document adapted from an AAMC publication (“Recommendations for Governance and Management of Institutional Animal Resources,” Association of American Medical Colleges and Association of American Universities, 1985). It is offered here only as an example of how an academic institution might choose to articulate individuals’ roles and responsibilities. The Guidelines may help improve coordination and communication among the various units and individuals within an institution involved in animal care and use, and assist personnel in their efforts to support research and instruction involving animals.

 

Discussion Question

Reconsider the survey question from the start of this Unit. Has your response changed?

 

Additional Resources

There are a number of excellent resources to help guide institutions and IACUCs in formulating institutional policy and executing their responsibilities.

The IACUC Handbook is a comprehensive, multi-authored text that examines all facets of IACUC responsibility. The question and answer format is especially useful, with answers that provide both specific regulatory references and comment/opinion.

Another comprehensive resource is the second edition of the IACUC Guidebook , from the Applied Research Ethics National Association (ARENA) and the Office of Laboratory Animal Welfare (OLAW). This revised edition “…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.”

The IACUC.org site, produced by the American Association for Laboratory Animal Science, is oriented towards IACUC members, but has well-organized links to a great deal of information on the regulations and training of personnel who work with animals.

The ResearchTraining.org site was developed by the Veteran’s Administration Office of Research and Development to meet mandates for research training, including “Essentials for IACUC Members.” It is offered free, and the course may be taken through the institution or as an unaffiliated “public” member.


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