Mammalian cell culture processes used for protein therapeutic manufacturing are initiated with vial thaw of cell banks, followed by seed train expansion to generate inoculum culminating into the production bioreactor step to generate the required product. Such a cell culture manufacturing process could take anywhere between 4-6 weeks. However, the last decade has witnessed advancement in cell lines and cell culture media enabling improvements in cell growth and productivity. By taking these improvements into account, conventional cell culture processes can be strategically improved by using higher seed densities during seed train expansion and production stage to shorten the overall manufacturing timelines.<br/>Here we present case studies that demonstrate the development of high seed-density (HSD) cell culture processes for two Chinese hamster ovary (CHO) cell lines expressing monoclonal antibodies (mAbs). The processes were seeded at high-densities, 2x - 10x higher than typical seed density, for seed train expansion and production phases. The transition to HSD process from a low seed density process offered several advantages. The HSD production processes for two CHO cell lines reached comparable titer yield by 11-12 days, while their respective low seed density process reached the same titer in 14 days. The strategy significantly shortened the overall culture duration, offering potential for increased utilization of the manufacturing/production facility. In one of KBI’s production suites, housing 2x2000L single-use bioreactors, facility utilization increases by 14% and 27% respectively for two or three days decrease in cell culture duration. In addition, HSD processes reduce the residence time of the product in bioreactor, which can modulate key product quality attributes that are impacted by culture duration such as glycosylation. Overall, this approach offers the opportunity to debottleneck the rate limiting step in a typical biopharmaceutical manufacturing facility and to increase manufacturing capacity significantly without requiring an alteration in the operational format.

High seed density cell culture processes to reduce manufacturing cycle times

255th National Meeting (2018)

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