Development of a new regulatory paradigm for well-characterized biotechnology-derived drugs and biological products

Abstract

Complete biochemical and biological characterization of biotechnology products is now required by the FDA and other regulatory authorities in support of applications for approval. A new regulatory paradigm for well-characterized biotechnology-derived drugs and biological products can be developed to harmonize the regulatory requirements of drugs and biological products and to replace the regulations originally promulgated for traditional biological products. Extensive characterization studies are generally not performed until a candidate product demonstrates the desired biological activity and lack of measurable toxicity in pre-clinical and early clinical studies. This raises a significant problem since a poorly characterized product may not be introduced into a commercial manufacturing facility due to the concern that adventitious agents or contaminants may cross contaminate other products. A simple and reliable algorithm for identifying and providing a reasonable amount of documentation for production and process changes has been sought by the biotechnology industry. Such an algorithm, in order to be effective, must be capable of determining the comparability of products manufactured by different procedures and defining the battery of tests necessary for complete product characterization at all phases of study. This research project began by examining such an analytical algorithm and benefited by the use of information gained through the author's experience with all submissions for biotechnology products approved by the FDA's Center for Biologics Evaluation and Research from the time of receipt of the first biotechnology product application. Validation of the analytical hypothesis was achieved through a biochemical and analytical characterization study of two cytokines at University of Maryland at Baltimore and the FDA, resulting in the design of a biotechnology Product Development Profile. This became a first step in efforts to define adequate characterization of products of biotechnology. Implementation of a new regulatory paradigm, which had not been attempted since the inception of the Public Health Service Act in 1944, was made possible by this research and the thoughtful integration of regulatory and laboratory science based on experience gained in over two decades of biotechnology-derived product regulation. The new regulatory paradigm has now been initiated for products derived from biotechnology processes capable of being well characterized.