USE OF ANIMALS IN BIOMEDICAL ENGINEERING RESEARCH

Jafar Vossoughi, PhD, John W. Karanian, PhD*

Biomed Research Foundation, 3616 Martins Dairy Circle, Olney, MD20832

*Laboratory of Cardiovascular and Interventional Therapeutics, CDRH, US-FDA

8401 Muirkirk Road, Laurel, MD20708

ABSTRACT

Bioengineers use animal models to support preclinical testing and evaluation of medical devices and implants, as well as, new drugs and therapeutics. Although animals play a significant role in medical research, biomedical engineers should not use this privilege as a routine evaluation method, but rather they should explore alternative methods to minimize or even eliminate animal use. It is well understood that medical devices and drugs improve the quality of human health and save lives, due in great part, to the knowledge obtained from preclinical animal studies. However, where possible, advances in alternative methodology should be used to minimize or eliminate traditional preclinical animal testing that is conducted in fulfillment of regulatory requirements for market access. For example, new approaches to toxicity and biocompatibility testing may be conducted in vitro using tissue bio-assays and cell culture technology. In addition, numerous mathematical and computer models may also be applicable and should be seriously considered as an alternative to animal studies. The use of animals in biomedical research must be considered a privilege that requires absolute compliance with all government and institutional regulations regarding animal care and use. All scientists must establish the rigor of their effort to first identify any alternative to animal use prior to applying institutional approval for an animal study. The interface between the ethics of animal use in biomedical research and the application of guidelines should be considered in view of government and institutional requirements.

PRECLINICAL/CLINICAL TRIALS

Prior to the start of the clinical research involving animals or humans, the investigating team must secure the appropriate approvals from the governing local institutions/boards. The use of animals in research is approved by theIACUC(Institutional Animal Care and Use Committee), whereas, the use of human subjects in research must be approved by the IRB (Institutional Review Board). Both committees are composed of researchers/scientists as well as ordinary individuals. Their main task, in the case of animal use, is to ensure that there is absolute need for animal use and that the animals are used in human manner and procedures are in place to eliminate or reduce pain and suffering of the animals. There are many other requirements that the research team has to meet such as adequate use of food and water as well as appropriate housing, lighting, etc. The animals must be treated under restrict rules and the animal facility must also be licensed by external accrediting organization.

Bioengineers use animal models to supportpreclinical testing and evaluation of medical devices and implants, as well as new drugs and therapeutics.

Purpose of Preclinical Studies:

  • Provision of reasonable evidence of safety (effectiveness) prior to human clinical trial
  • Model selection is critical
  • in vivo feasibility (define orrefine a model…refine the technology)
  • in vivo safety and effectiveness (S&E) (refine technology, S&E study)

ETHICS OF ANIMAL USE IN RESEARCH

Although animals play a significant role in medical research, the study design regarding animal use and their number should always follow the three R’s:

  • Replacement (replace live vertebrates with lower forms or replace animals with non animal models, such as tissue cultures,mathematical and computer models, if possible)
  • Reduction (use absolute minimum number of animals to obtain statistically valid results)
  • Refinement(make sure to eliminate or minimize potential pain and suffering)

It is well understood that medical devices and drugs improve the quality of human health and save lives, due in great part, to the knowledge obtained from preclinical animal studies. However, where possible, advances in alternative methodology should be used to minimize or eliminate traditional preclinical animal testing. For example:

  • The number of animals used for testing, that is conducted in fulfillment of regulatory requirements for market access, must be kept to an absolute minimum.
  • Toxicity and biocompatibility testing may be conducted in vitro using tissuebio-assays and cell culture technology.
  • Recent findings in the area of stem cell research, for example, indicate the use of embryonic plasma may be predictive, therefore, eliminating the need for the use of stem cells.
  • In addition, numerous mathematical and computer models may also be applicable and should be seriously considered as an alternative to animal studies.
  • All scientists must establish the rigor of their effort to first identify any alternative to animal use prior to receiving institutional approval for an animal study.

There is an interface between the ethics of animal use in biomedical research and the application of guidelines in view of government and institutional requirements. Although there are a large number of booklets and printed materials, the following are the minimum documents that any biomedical researcher should consult prior to use of any research animal:

  • Regulations and policies regarding animal care and use (they are defined in the Guide for the Care and Use of Laboratory Animals(ILAR, NRC, 1996))
  • The Animal Welfare Regulations(AWA, 9CFR 1985)
  • The Public Health Service Policy on Humane Care and Use of Laboratory Animals(PHS, 1996)

These guides endorse the responsibilities of investigators as stated in the U.S. Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research and Training(IRAC, 1985). Responsible conduct in animal research remains an unquestionable requirement of scientists/bioengineers conducting preclinical animal research.

In the case of medical devices, drugs and biologics, there are additional regulations that may require animal use that are imposed by the US-Food and Drug Administration:

  • Protect Public Health

Ensure that devices, drugs and biologics are safe, effective and properly manufactured

  • Promote Public Health

Encourage technological innovation anddevelopment

Ensure availability of accurate information

The use of animals in biomedical research must be considered a privilege that requires absolute compliance with all government and institutional regulations regarding animal care and use.

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