Ann L. Lee, Kathleen Champion Francissen, Bob Kiss, and Brad Snedecor. Process Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080
In 1987, Genentech gained FDA licensure for the first CHO cell-derived recombinant protein product, tissue plasminogen activator (rt-PA), for treatment of acute myocardial infarction. Over the next twenty years, CHO technology served as a platform for launching another nine products to treat medical conditions ranging from non-Hodgkin’s lymphoma to asthma to breast cancer to metastatic colorectal cancer, therapeutics which have helped us to meet our mission of developing novel medicines for patients. Key advances were made by scientists and engineers working in CHO bioprocess development to commercialize these products and to ensure sufficient supply to meet patient demand. These milestones include suspension and serum-free adaptation, bioprocess strategies that avoid triggering apoptosis, and media development. These have enabled higher cell densities, better viabilities, higher cell titers and yields, as well as scale up to 20,000+L bioreactors to be achieved without sacrificing product quality. These advances in bioprocesses also incorporated improvements in downstream purification procesesses, such as development of centrifuge harvest to overcome limitations of filtration at large scale and at high debris loads. Efficient large-scale ion exchange chromatography methods were developed to allow robust removal of high loads of cell-derived impurities. This journey through CHO bioprocess development at Genentech over the past two decades will be described.