(485bn) Clone Selection in Chemically Defined Media for a CHO MAb Process

During clone selection of a CHO-produced monoclonal antibody (MAb), the primary goals were to maintain volumetric productivity and product quality in chemically defined media (CDM) when compared to a non-CDM process. The clone selection process was conducted with our current in-house CHO production host as well as a newly generated CHO cell line and was performed using high-throughput screening in tubes, shake flask cultures and 2-L fermentors. The best clones were selected based on productivity and product quality in CDM and media containing hydrolysate (animal and / or plant origin). The focus of this project was to ensure that the product quality generated from these newly optimized conditions and processes met the previously accepted target ranges based on product potency and binding affinity towards the target receptor. Specifically, the impact of media components and process parameters upon product quality (e.g. glycosylation, charge variants and aggregation) were evaluated. Productivity increases by process manipulation were determined by a DOE approach targeting the fed-batch feeding strategy, temperature shift parameters and production culture seeding density. For the selected clone, the final titer was increased by 1.5-fold in CDM through this process optimization. The increased productivity was achieved by evaluating chemically defined in-house media formulations supplemented with specific amino acids, nucleosides, trace elements and insulin. This project permitted additional understanding of the use of high-throughput screening tools and our in-house CDM.