Use of Enzymes in the Manufacture of Active Pharmaceutical Ingredients—A Science and Safety-Based Approach To Ensure Patient Safety and Drug Quality

TLDR

Biocatalysis is increasingly used to manufacture active pharmaceutical ingredients, yet clarity on quality and regulatory expectations remains limited, hindering broader adoption. The commentary aims to outline practical, risk‑based strategies for employing biocatalysis in small‑molecule API production and to solicit industry input for a future white paper. It proposes a scientific, risk‑based framework that aligns biocatalytic processes with drug quality and patient safety requirements.

Abstract

A significant number of marketed pharmaceuticals contain active pharmaceutical ingredients that are manufactured in part using biocatalysis as a key enabling technology. The utilization of biocatalysis is growing due to significant advances in technologies for enzyme discovery, supply, and improvement, as well as an increased focus on applications for chiral drugs and green chemistry. Nevertheless, there still remains a lack of clarity around quality and regulatory expectations when using biotransformations in research and manufacturing, and this lack of clarity can be a barrier to the uptake and adoption of biocatalysis. This commentary will explore and offer some rational, coherent, and achievable strategies for the use of biocatalysis in the manufacture of small molecule active pharmaceutical ingredients (APIs) based on a scientific, risk-based approach to drug quality and patient safety. We also seek to invite other interested parties to contact us with their views to add to the topics discussed here with the goal of expanding these thoughts into an industry-based white paper.