Regulatory philosophy for comparability protocols.

Abstract

Continuing improvements in analytical biochemistry and biophysics make it reasonable to evaluate their use in obviating the need to use clinical studies for confirmation of product comparability following a change in manufacturing. It is essential to consider these analytical techniques in the context of specific manufacturing processes with well-defined parameters and specific products that have been characterized fully. Existing analytical technologies continue to be limited in dynamic range, so that small amounts of potentially harmful impurities may not be detected. In most cases, biochemical or biophysical techniques are neither sensitive nor robust enough to substitute entirely for some sort of biological potency assay, though there are important exceptions. Prudent design of comparability protocols will thus reflect the international consensus set down by ICH that sets of specifications on which such protocols are based comprise "one part of a total strategy designed to ensure product quality and consistency. Other parts of this strategy include thorough product characterization during development,...adherence to Good Manufacturing Practices, a validated manufacturing process, raw materials testing, in-process testing," and so forth.