Global regulatory considerations for unified assay specifications

When developing a biotechnology product for global registration, there are several aspects to evaluate in an effort to unify specifications. These include differences between the United States, Europe and Japan, and Rest-of-World (ROW) countries with regard to the respective regulatory guidelines and pharmacopoeias in force, the state-of-the-art of product testing analytical methods, and the interval between submitting a registration dossier to different countries. In terms of regulatory guidelines, one country may have a monograph or required specifications for particular tests, for example the potency that a product has to meet before clinical trials can be initiated. For pharmacopoeias, different assay methods are required for sterility, general safety, and pyrogen testing, so that one may have to test a specific lot of a product at two or three different times to evaluate the same parameter, because of specific testing differences required for each country's pharmacopoeia. In addition, the state of analytical methods is always evolving and better analytical techniques become available. Sometimes, from starting with one set of tests, and based on the time in development, new tests may be added to the existing list of release specifications, because new analytical techniques have become available. Examining the global registration approval process for Betaseron, (interferon beta-1b) illustrates when specifications were able to be unified and when they were not.