Case Studies Illustrating a Science and Risk-Based Approach to Ensuring Drug Quality When Using Enzymes in the Manufacture of Active Pharmaceuticals Ingredients for Oral Dosage Form

Biocatalysis is essentially the use of enzymes to perform chemical transformations on organic compounds and has been exploited for applications in various industries including food, fine chemicals, agrochemicals, and pharmaceuticals. Due to their selectivity and ability to operate under mild conditions, enzymes offer clear advantages for efficient sustainable manufacturing processes. Rapid development of enabling technologies including gene mining, molecular biology, biocatalyst evolution, and bioprocess engineering, has created opportunities to use biocatalysis more broadly for the manufacture of small molecule intermediates and APIs (active pharmaceutical ingredients). To facilitate the adoption of biocatalysis for API manufacture and address a perceived lack of regulatory clarity, several of the current authors published a science and risk based approach to ensuring patient safety and drug quality when using biocatalysis (Org. Process Res. Dev. 2012, 16, 1986−1993). Since this publication, consultation of multiple users and stakeholders in the biocatalysis community has expanded on key guidance and specific approaches, as well as providing real examples of regulatory review and approval in this article. Our ultimate goal as highlighted in this publication is to provide a clear path and knowledge base to enable a robust and sound science and risk-based approach for utilizing biocatalysis whenever appropriate for the manufacture of small molecule pharmaceuticals.