Recently, there has been a significant increase in the use of biocatalytic steps to manufacture small molecule drug substances. Currently, there are no clear guidelines from agencies on the control of residual impurities (e.g., proteins, DNA/RNA, etc.) in small molecule API manufacture. Furthermore, the control strategy will differ drastically based on intended mechanism of delivery (i.e., oral vs parenteral). This talk will aim to cover the challenges, both analytical and regulatory, associated with large molecule impurities introduced with the crude enzyme lysates used for biocatalytic steps. We propose general limits for total protein content in the final API and discuss a workflow encompassing in silico and in vitro experiments to minimize risk for higher risk parenterally-delivered compounds. This approach is a scientific- and risk-based approach to ensure product quality and patient safety in small molecule APIs generated from biocatalytic routes.
Describe the analytical and regulatory challenges currently associated with the manufacture of small molecule APIs via biocatalytic routes.
Consider a general strategy for the control of residual proteins in orally and non-orally dosed drug substances using novel in vitro and algorithm-based approaches.
Discuss the risks and mitigation strategies for residual proteins in parenteral APIs.