Recent progressions in cell line development, media design, and process optimization have shown significant improvements to the cell culture production process and monoclonal antibody production. Correspondingly, the increased product titer and cell densities also pose a challenge on cell removal and harvest clarification. This study was designed to evaluate different methods of clarification of a CHO cell culture harvest in terms of capacity, product recovery, product quality, and economic efficiency. Different clarification processes were tested using a single pool of cell culture harvest from a proprietary fed-batch process. The different methodologies tested include centrifugation, two-stage depth filtration, a combination of centrifugation with single stage depth filtration, and a combination of flocculation with single stage depth filtration. The maximum capacity of each clarification method was measured by P-max determination. Any change in total product amount, turbidity, lactate dehydrogenase (LDH), and host cell proteins (HCPs) were evaluated before and after each clarification step to compare process efficiency. Up to 50% difference in turbidity and 20% difference in HCPs was observed between different methods of clarification. LDH levels were similar between methods, indicating no change in amount of cell lysis between different methods. Product quality attributes were also monitored to evaluate any impact caused by the different methods. An economic analysis was done based on the information obtained from the experiments and pricing data from vendor to determine if a change to the current platform was warranted. Results from the evaluation helped to further characterize the cell culture harvest platform process to accommodate variable requirements of mammalian cell culture processes, particularly those yielding high cell densities and product titers. Keywords CHO; Monoclonal antibody; Cell culture harvest; Clarification; Depth filtration; Centrifugation; Flocculation

Clarification platform evaluation and optimization

249th National Meeting (2015)

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