A Systematic Development Approach to Optimize and Control Biopharmaceutical Product Quality

The complexity of recombinant protein manufacturing processes, including expression systems, cell culture process conditions, and choice of media and feeds, present signifi-cant challenges to achieve desired product quality of bio-pharmaceuticals. To address these challenges, Fujifilm Diosynth Biotechnologies (FDB) has developed a unique systematic approach of combining “Media Toolbox” methodology, key chemical components, and cell culture bioprocess “know-how” to optimize and control manufacturing condi-tions that promote the desired product quality profiles of recombinant proteins.

Case studies are presented to highlight the efficacy of this approach. Case 1 represents a successful application of the “Media Toolbox” consisting of high-quality media and feeds targeting a variety of CHO parental cell lines established from FDB’s Innovation program. By using this methodology to optimize a Phase 3 manufacturing process, in less than three months, we not only improved NAb titers ~ 5-fold (> 5 g/L) as compared to original cell culture process, but matched the key product quality attributes including all examined glycan structures. Control was demonstrated through scale reproducibility from bench-scale (2L, 10L bioreactors) to manufacturing scale (2000L bioreactor). Also shown are examples using knowledge of nutrient components (i.e. sugars, trace elements) and cell culture process conditions to further optimize and control product quality in a “targeted” manner.