Refinement, reduction, and replacement of animal use for regulatory testing: current best scientific practices for the evaluation of safety and potency of biologicals.

Abstract

Biologicals, such as vaccines, require batch-related quality control to ensure their safety and potency. Part of quality control is based on animal models; consequently, the use of laboratory animals is extensive. In this paper, the characteristics of animal testing and its regulatory framework are described. Current trends in the development and implementation of alternatives to animal use are discussed. These trends include in vitro antigen quantification tests, serological approaches, the use of humane endpoints, and application of the principles of good laboratory animal practice. Emphasis is also given to a change of regulatory policies on licensing authorization. It is concluded that 3Rs' progress is frustratingly slow and that a real breakthrough in terms of animal reduction will be possible only after adoption of the "consistency approach," a new concept of vaccine quality control. This consistency approach has become state-of-the-art for the new generations of vaccines. Full implementation of the rules of good manufacturing practice and quality assurance would also allow the application of a consistency approach to quality control of conventionally produced vaccines.