Alternatives to the Use of Animals in Biomedical Research

In the preamble to the Federal Animal Welfare Act, Congress acknowledges that animals are instrumental in biomedical research and education and that meeting public concern for the care and treatment of laboratory animals is important for ensuring that research will continue to advance. It is further stated that there is opportunity for developing research methodologies that do not use animals and such alternative measures can result in more productive use of Federal funds.

One of the requirements of the 1985 amendment to the AWA is that principle investigators will consider alternatives to procedures likely to produce pain or distress in laboratory animals. These regulations [9 CFR Sec. 2.31(d)(1)] state:

"The IACUC shall determine that proposed activities or significant changes to ongoing activities meet the following requirements:

1. The principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain or distress to the animals, and has provided a written narrative description of the methods and sources, e.g., the Animal Welfare Information Center, used to determine that alternatives were not available;

 
2. The principal investigator has provided written assurance that the activities do not unnecessarily duplicate previous experiments"

Replacement, Reduction, and Refinement.

Replacement involves replacing the use of living animals with:

1. animals low on the phylogenetic scale i.e. invertebrates, insects;
2. utilizing in-vitro techniques such as organ, tissue, or cell culture;
3. nonanimal living systems i.e. retroviral gene transfer; or
4. nonliving systems i.e. computer modeling.

Refinement is the principle of refining an existing procedure or technique so as to minimize the level of pain or distress endured by the animal. Refinement may involve decreasing invasiveness of a procedure or utilizing noninvasive technology, improved technique, or better control of pain or distress.

Information on alternatives may be obtained through numerous references including current literature, scientific databases, and other sources such as:

• Animal Welfare Information Center
• National Agricultural Library
• National Library of Medicine
• The Johns Hopkins Center for Alternatives to Animal Testing
• Scientists Center for Animal Welfare

The 1985 amendments to the Animal Welfare Act have generated much discussion and, in some cases, confusion with regard to compliance. The responsibilities of the Principal Investigator and the Institutional Animal Care and Use Committee is considering alternative methods and unnecessary duplication of research are two areas of concern. The following is a list of questions that are frequently asked by the regulated community. The answers provided are based on the regulatory requirements of the 1985 Animal Welfare Act.

Q. "The Principal Investigator (PI) has provided written assurance that his or her research activities do not unnecessarily duplicate previous experiments." Will this statement signed by the PI satisfy the requirements or is evidence for literature review necessary?

A. The animal welfare regulations (9CFR Sec. 2.31 (d)(1) (iii)) state that is the Institutional Animal Care and Use Committee's (IACUC's) responsibility to determine that the investigator has provided "written assurance that the activities do not unnecessarily duplicate previous experiments" A written assurance consisting of a statement signed by the PI will satisfy this regulation. It is up to the IACUC, however, to determine what type of information should be included in the investigator's assurance. This may vary based on the needs and experience of the IACUC.

Q. How does the U. S. Department of Agriculture (USDA) define alternatives?

A. The regulations state that the IACUC must determine whether the PI has considered alternatives to procedures that cause more than momentary or slight pain or distress to animals. Certainly, alternatives to animal use are important considerations; however, the regulations only specify alternatives to painful procedures.

Q. What are the information sources that can be used to search for alternatives?

A. Library resources, computer databases, other researchers, texts, and journals are all sources which may be used to search for alternatives.

Q. How can an IACUC evaluate these sources?

A. It is not easy for the IACUC to evaluate the "written narrative description of the methods and sources used to determine that alternatives were not available." The intent of this regulation is not that the IACUC evaluate the databases or sources cited, but that the PI consider alternatives to procedures that may cause pain. Questions that should be addressed by the PI are: Is there a nonsurgical or noninvasive model? Is there a model that does not require survival surgery? Is there an in-vitro model? The investigator my wish to include the following items in the narrative: the database(s) searched, the keywords used in the search, and selected references on animal models or alternatives.

Q. How do investigators [such as individuals within the Environmental Protection Agency (EPA) or the Food and Drug Administration (FDA)] conducting testing procedures that are required by regulations consider alternatives?

A. The investigators in these facilities should consider alternatives as any other investigator does. However, the alternatives may not be feasible because the regulations do not allow for any alternative tests or procedures.

Q. Is performing a published research protocol in order to ensure comparable results and technical competency considered unnecessary duplication of research?

A. Such replication often provides a foundation for the validation and advancement of research. The animal welfare regulations (9CFR Sec 2.31 (d)(10(iii)) state that it is the IACUC's responsibility to determine that the investigator has provided "assurance that the activities do not unnecessarily duplicate previous experiments." This example is not interpreted as unnecessary duplication of research.

Q. Is a teaching experiment considered duplicative research?

A. Teaching experiments are not considered duplicative because each time a procedure is performed for a new group of students or new audience, new knowledge is gained.

The Principal Investigator must address the areas of alternative procedures and unnecessary duplication of research and the IACUC must determine whether the issues have been satisfactorily addressed. Investigators should be aware of sources of information on alternatives and the type of information required by the IACUC. It is important that the PI and the IACUC work together to meet the regulator requirements.

The 1985 amendments to the Animal Welfare Act and the resulting regulations require that the primary investigator consider alternatives when submitting a research protocol to the Animal Care and Use Committee. While the Animal Welfare Information Center is stated as a source for information on alternatives, there are other resources available to aid the regulated community in complying with the regulations. The following list, which contains contact information for several of the organizations, has been reproduced from a AWIC Fact Sheet. Copies of this Fact Sheet are available from AWIC.

Animal Health, Well-Being, and Rights

Alternatives to Animal Use

Animal Welfare Information Center
(AWIC)
National Agricultural Library
Room 205
Beltsville, MD 20705-2351
301-344-3212; FAX: 301-344
P.O. Box 3650
Washington, D.C. 20007
202-337-2332; FAX: 202-338-9478

Canadian Council on Animal Care
151 Slater
Ottawa, Ontario K1P 5H3 Canada
613-238-4031; FAX: 613-238-2837

Center for Alternatives to Animal Testing
Johns Hopkins School of Public Health
615 N. Wolfe Street
Baltimore, MD 21205
301-955-3343; FAX: 301-955-0258

Center for Animals and Public Policy
Tufts University
200 Westboro Road
North Grafton, MA 01535
508-839-5302 ext. 4750; FAX: 508-839-2953

Commission on Life Sciences
Inst. for Laboratory Animal Resources (ILAR)
2100 Constitution Avenue
Washington, D.C. 20418
202-334-2590

Hastings Center
255 Elm Road
Briarcliff Manor, NY 10510
914-762-8500; FAX 914-762-2124

IACUC Resources

J. F. Morgan Foundation
Health and Welfare Canada
Tunneys Pasture
Ottawa K1A 0L2 Canada
613-957-2399; FAX: 613-957-1907

National Institutes of Health
National Library of Medicine
Bethesda, MD 20894
301-496-3147; FAX: 301-480-3537

Public Responsibility in Medicine & Research
(PRIM&R)
132 Boylston Street - 4th Floor
Boston, MA 02116
617-423-4112

Scientists Center for Animal Welfare
(SCAW)
4805 St. Elmo Avenue
Bethesda, MD 20814
301-654-6390