(249a) Recent Challenges and Opportunities for Biotechnology: A Perspective From Commercial Manufacturing

It has been three decades since the first biopharmaceutical, recombinant human insulin, was licensed by the US Food and Drug Administration. Since then, biopharmaceutical industry has become the fastest growing, most dynamic and technology-intensive sector in the biomedical field. Mammalian cell culture remains the main source for antibody or therapeutic protein production and has demonstrated the capability to produce therapeutic recombinant proteins in large quantity.

For stable protein products like monoclonal antibodies, fed-batch processing has been widely accepted as a platform technology for large-scale manufacturing due to good process robustness, scalability and ease of operation. With the recent improvement in cell line engineering and cell culture media and process optimization to increase cell specific productivity, viable cell density, and culture longevity, titers have increased from below 1 g/L in the early 1990s to over 8-10 g/L more recently. Industry has moved to using platform technology, maximizing the speed to clinic and product launch. With this, the process optimization may be shifted from late stage process development to post launch (i.e. before the build-up of the newly-launched product’s demand peak, or transfer the production to a second plant). This change in development philosophy increases the need to build a more experienced and scientifically-minded technical supporting group at commercial manufacturing site.   

Several case studies will be discussed to demonstrate the recent challenges encountered in the commercial manufacturing, including the development of a barrier for adventitious agent, raw material variation, increased product mix, and implementation of quality by design. Overall, the focus of commercial manufacturing is on product quality and process consistency through improved process and product understanding.