Intensification of the CHO cell culture production bioreactor to achieve higher titers requires a high viable cell density (VCD) seed source. This can be achieved by utilizing a perfusion N-1 seed bioreactor to grow cells to a very high density while maintaining high viabilities suitable for the transfer to production. In developing a perfusion N-1 process for multiple mAbs, we utilized a PAT tool, an in-line biocapacitance probe, to automatically control the perfusion rate based on the number of cells in the bioreactor at any given time. Using this biocapacitance probe in development of 6 mAbs, we established a platform process with the goal of speeding up development and were able to determine optimal cell specific perfusion rate (CSPR) and inoculation density within 2 or 3 experiments. The online biocapacitance reading correlated very well to the offline VCD for all mAbs tested, with final cell densities reaching up to 130×106 cells/mL. Online control of the CSPR allowed for efficient media usage while maintaining cell health (viabilities above &gt;90%). Furthermore, we successfully applied the biocapacitance controlled N-1 perfusion strategy developed at benchtop bioreactor scale to manufacturing scale. Thus, implementing a platform process development approach based on the biocapacitance probe to control perfusion rates led to efficient process development of perfusion N-1 seed cultures for supporting very high cell density CHO cell cultures.

Platform development of perfusion N-1 bioreactor using in-line biocapacitance probe

ACS Spring 2022

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