Understanding and Controlling the API Form/Powder Property Risks in Drug Substance and Product Processes

Dr Shawn Yin
Scientific Director, Materials Science and Engineering, Drug Product & Development,
Bristol-Myers Squibb Co.
1 Squibb Dr., New Brunswick, NJ 08903

Abstract

It is well known that some key drug substance physical properties, like crystal form, crystallinity, size, morphology, etc., can be altered during drug substance and/or product processes, and potentially during the product shelf life. Therefore, acquiring a good knowledge of how both the DS and DP process impacting on these critical product quality attributes is one of the key development activities, aiming at ensuring a success product development and bringing a robust product to the market. This presentation described, via real development/manufacturing examples, several risk factors including regulatory risk of DS/DP process induced API physical changes. These risks are assessed based on physical characteristics of material single crystal structures, surface/bulk physical characterizations and their relevant biopharmaceutical properties. The impacts of these risks on DS/DP CMC activities, product quality and patients are also discussed.