A Risk-Based Approach to the Application of Biocatalysis for Manufacture of Small Molecule APIs

Enzymes are being routinely used for synthesis of organic molecules including small molecule APIs as they offer significant benefits (e.g. cheaper, greener, more selective, higher yielding, safer etc) over conventional chemo-catalytic processses. Potential impurities that could occur in products of enzymatic synthesis depend on several factors such as the enzyme source (plant, animal, microbial), the manufacturing process for the enzyme, and the enzymatic reaction step, and include proteins (enzyme and host cell), nucleic acids, endotoxins, and bioburden. Current regulatory guidance does not adequately address enzyme related impurities for small molecule APIs and this lack of clear guidance has been reflected in regulatory queries received for a number of Pfizer enzymatic regulatory submissions. The presentation will highlight the risk assessment framework, built around Quality By Design and drug safety principles, used within Pfizer and present case studies from two recent commercial filings