Process intensification in biopharmaceutical process development and production – an industrial perspective

Abstract

Abstract Process intensification aims to increase productivity in biologics manufacturing. Significant progress has been made in academia, the biopharmaceutical industry, and by the regulatory guidance since the 2000s. Process intensification can include all unit operations of a drug substance manufacturing process. The applied upstream concepts have consequences on the downstream process (DSP). The DSP process must manage larger product amounts while ensuring the required quality and impurity profiles, and cope with the available time frame as per scheduling requirements in a facility. Further, intensification in DSP is not based on a single technology only but rather on various technologies. This contribution provides an industry perspective on process intensification, describing basic concepts, technical and engineering aspects as well as the impact on the manufacturing process given existing facilities and a product portfolio to be manufactured. It also covers scientific approaches that support understanding and design of intensified bioprocesses. From an implementation perspective, the technologies used for intensification must be robust, scalable, and suitable for commercial manufacturing. Specific examples for a high seeding density fed batch (using N-1 perfusion) and a continuous process are provided for Chinese hamster ovary (CHO) cells producing therapeutic antibodies. Economic and sustainability aspects are addressed as well. Process intensification in an industrial environment is complex and many factors need to be considered, ranging from characteristics of a specific molecule to its commercial manufacturing at internal or external sites for global or regional markets.