Bioethical Approval of Animal Care and Use in Research (Part 1)

Institutional Animal Care and Use Committees ( ACUCs ) in research and experimental models play an important role in the application of the Laws on animal research in the United States . Typically, this system operates similarly in different countries , but under different names . For example, in Canada the specific name is the University Animal Care Committee ( UACC ) , while in the United Kingdom it would be the Animal Welfare and Ethical Review Body ( AWERB ).

Most research involving animal experimentation in the United States is funded by the United States National Institutes of Health ‐ NIH. Mỹ or, to a lesser extent , other federal centers. The NIH Office Office of Laboratory Animal Welfare‐ OLAW is mandated by law to develop policies that reflect the role of the Ethics Committee on Animal Care and Use (IACUC) . Any institution that uses certain types of animals for federally funded laboratory research must have an Ethics Committee on Animal Care and Use (IACUC).

Each local IACUC is responsible for reviewing research protocols and performing animal care and use assessments , including facility inspections as required by law . The parallel and equivalent institutional ethics board (IRB) responsible for overseeing human research funded by the U.S. federal government is the Medical Ethics Board (IRB).

History of the Ethics Committees for the Care and Use of Animals (IACUCs)

The history of the IACUCs grew out of the history of animal welfare regulation in the United States . Prior to 1963, regulations were implemented entirely by researchers and research laboratories whose animal care policies were inconsistent with standards of care. A group of veterinarians formed the Animal Care Policies ( ACP ) and began work in 1961 .

By 1963 , they had published the first edition of the Guide for the Care and Use of Laboratory Animals , referred to as the Guide. Subsequent editions of the Guide were supported by the NIH and published by the Institute of Laboratory Animal Research of the National Academy of Sciences. The Guide is currently in its eighth edition . An accreditation committee was established in 1963 and it was established independently from the ACP , as AAALAC ( Assessment and Accreditation of Laboratory Animal Care International) , the American Association for the Accreditation of Laboratory Animal Care . In 1996, this committee changed its name to the “Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)”.

A series of reports on the poor state of animal welfare in the United States led to a major article in Life magazine in 1966. Public opinion was particularly stirred by the case of a pet dog that was stolen in Pennsylvania and later died during an experimental surgery at a New York hospital . As a result , through the efforts of Representative Joseph Y. Resnick, Congress enacted the Animal Welfare Act (1966), designating the USDA as the responsible agency. The agency inspected facilities that used animals, but did not inspect or regulate private laboratories .

In 1971, the Animal Welfare Act was amended and compliance by institutions can be achieved through the Animal Care Committee or through AAALAC accreditation. Compliance requires adherence to the Guidelines, the Animal Welfare Act, and the additional “Principles for the Use of Laboratory Animals”.

In 1979, a US Public Health Service (PHS) policy was adopted requiring an animal care committee for each funded institution that uses animals and expanding the protected species to include all vertebrates. The animal care committee was required to have five members with expertise in managing animal welfare at the institution , including at least one veterinarian.

The term IACUC was formally introduced in 1986 with the amendment to the Animal Welfare Act and corresponding changes in PHS policy. Although much of the animal welfare law comes from the Animal Welfare Act enforced by the USDA, all of the IACUC regulations come from PHS Policy. Inspections of facilities of animal ‐using establishments are required twice a year. Thus, the modern component of the IACUC was established .

Composition of Animal Care and Use Ethics Committees (IACUCs)

The IACUC must have a minimum of three members, appointed by the Executive Director of the research facility. Appointed members must have the expertise to manage animal care at the facility . Membership requirements, as defined in 9 CFR §2.31 are as follows:

1. The Committee shall consist of a Chairman and at least two other members;
2. One of these members must be a veterinarian with training or experience related to laboratory animal research;
3. A member may have no relationship with that organization other than service on the IACUC.

Additionally, if the IACUCs committee consists of more than three members, no more than three members may come from the same administrative unit of that institution .

IACUC Activities

Each local IACUC reviews research protocols and conducts an assessment of the institution’s animal care practices. The assessment includes an inspection of all animal use facilities every six months . The IACUC reports annually to the NIH Office of Laboratory Animal Welfare (OLAW) and is assigned an animal welfare assurance number by OLAW , without which the use of animals in federally funded research may not be performed . The IACUC must report to OLAW any noncompliance with strict animal use protocols, as well as the actions the IACUC has taken to correct the noncompliance .

Evaluation process

Each animal use protocol (AUP) must be reviewed by the entire IACUC committee at least once every three years and may be reviewed more frequently if requested by the IACUCs committee. The protocol must include at least the following:

1. Identify the species and number of animals expected to be used;
2. The rationale relating to the animal as well as the appropriateness of the species and quantity used;
3. A full description of the proposed use of the animal;
4. A description of procedures designed to ensure that discomfort and injury to animals will be limited to the minimum (unavoidable) when performing scientifically valid research; and that analgesics, anesthetics, and sedatives will be used when indicated and appropriate to minimize discomfort and pain to animals.
5. A description of any euthanasia methods that will be used.

When reviewing, the IACUC is required to ensure that the proposed work falls within the OLAW Animal Welfare Assurance and includes the following points:

1. Animal procedures will avoid or minimize discomfort, stress, and pain to animals, consistent with sound research design;
2. Procedures that may cause temporary or mild pain or discomfort to animals shall be performed with appropriate sedation, analgesia or anesthesia, unless the procedure is justified in writing by the investigator for scientific reasons;
3. Animals that would otherwise be suffering severe or chronic pain or unrelieved stress shall be painlessly “euthanized” at the end of the procedure or, if appropriate, during the procedure;
4. The living conditions of the animals shall be appropriate to their species and shall contribute to their health and comfort. The housing, feeding and non‐medical care of the animals shall be managed by a veterinarian or scientist trained and experienced in the proper care, handling and use of the species being maintained or studied;
5. Medical care for animals is available and provided as needed by a qualified veterinarian;
6. Personnel performing procedures on animals being maintained or researched must be appropriately qualified and trained in such procedures;
7. The methods of euthanasia used will be consistent with the recommendations of the American Veterinary Medical Association ( AVMA ) Council on Euthanasia ( from PDF file), unless the investigator provides a written explanation for deviation for scientific reasons.

From the 3R to the 4R and 5R principles and the additional 6R version in the use of research animals

Figure 2a. The 3R principles in research include Replacement (which means that if animals can be replaced in research or experiment, that is best); Reduction (which means that the number of experimental animals should be reduced to the minimum level, that is best); Refinement (which means that when we manipulate experiments or experiments on animals, we must do it gently, minimizing pain).