This work summarizes the implementation of perfusion technology at the seed bioreactor stage to reduce a 14-day fed-batch process down to 10 days, and proposes a large scale stainless facility model to implement perfusion technology in a legacy product. Any reduction in the time it takes a fed batch Chinese Hamster Ovary (CHO) culture process to go from the production step to harvest can improve a manufacturing facility’s cadence. Even with an improved cadence, manufacturing facilities can still experience timeline delays of hours or days in a process. Unlike CHO processes that reach final N-1 viable cell densities (VCD) &lt; 10 million cells/mL, a couple of hours of variability in a high density N-1 timeline can impact the split ratio of the production bioreactor step.<br/><br/>An evaluation that demonstrates how flexible the final VCD of a high density N-1 CHO culture is necessary to understand the impact on the production step. We sought to evaluate the N-1 stage final VCD of a high density N-1 culture in an Fc-fusion CHO cell process with the application of Alternating Tangential Flow (ATF) technology. Using ATF, CHO culture was grown to greater than 10.0 x 10<sup>6</sup> cells/mL and transferred to the production stage at varying final N-1 VCDs. To further evaluate the impact of perfusion at the N-1 step metabolomic results from an N-1 final VCD varying from 10-40 million cells/mL are summarized alongside production bioreactor step attributes. This work demonstrates the robustness of ATF technology application at the N-1 step and capability to reduce the production bioreactor step duration.

Evaluation of perfused high density seed bioreactor step of a legacy biologics process

255th National Meeting (2018)

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