Application of the consistency approach to reduce animal use in vaccine potency testing

Biologics are usually produced from live organisms, and the manufacturing process often involves a degree of natural variability. Characterization of biologics such as vaccines is inherently difficult due to the complex molecular structure of the antigens they contain and the presence of excipients such as preservatives and adjuvants that can interfere with testing. Therefore, each batch, lot, or serial produced must be tested before market release to ensure that the product complies with regulatory standards. This batch release testing emphasizes quality control of the final product and may be characterized by an extensive use of laboratory animals. The consistency approach is based upon the principle that the quality of a biologic is the result of the strict application of a quality system and consistent production. Subsequent batches are determined to be similar to clinically evaluated batches and therefore acceptable for release through the in-process testing that comprises this quality system. The European Centre for Validation of Alternative Methods (ECVAM) organized international workshops in 2006 and 2010 to discuss the consistency approach and its potential to reduce the number of animals used in testing of biological products. This paper provides an overview of these workshops.