Fed‐batch performance profiles for mAb production using different intensified N − 1 seed strategies are CHO cell‐line dependent

Abstract

AbstractRecent optimizations of cell culture processes have focused on the final seed scale‐up step (N − 1 stage) used to inoculate the production bioreactor (N‐stage bioreactor) to enable higher inoculation cell densities (2–20 × 106 cells/mL), which could shorten the production culture duration and/or increase the volumetric productivity. N − 1 seed process intensification can be achieved by either non‐perfusion (enriched‐batch or fed‐batch) or perfusion culture to reach those higher final N − 1 viable cell densities (VCD). In this study, we evaluated how different N − 1 intensification strategies, specifically enriched‐batch (EB) N − 1 versus perfusion N − 1, affect cell growth profiles and monoclonal antibody (mAb) productivity in the final N‐stage production bioreactor operated in fed‐batch mode. Three representative Chinese Hamster Ovary (CHO) cell lines producing different mAbs were cultured using either EB or perfusion N − 1 seeds and found that the N‐stage cell growth and mAb productivities were comparable between EB N − 1 and perfusion N − 1 conditions for two of the cell lines but were very different for the third. In addition, within the two similar cell growth cell lines, differences in cell‐specific productivity were observed. This suggests that the impact of the N − 1 intensification process on production was cell‐line dependent. This study revealed that the N − 1 intensification strategy and the state of seeds from the different N − 1 conditions may affect the outcome of the N production stage, and thus, the choice of N − 1 intensification strategy could be a new target for future upstream optimization of mAb production.