In fed-batch production, the majority of the product is generated after the growth phase, inherently lowering volumetric productivity.  We can improve volumetric productivity by shifting the growth phase from production into the seed train.  Since it is difficult to sustain high viable cell densities (VCDs) using traditional batch seed train cultures, we use perfusion technology at the N-1 seed train stage. We performed perfusion N-1 seed cultures using two different cell lines. Exponential growth was observed throughout the N-1 duration, with Cell Line A reaching 2x its peak fed-batch VCD and Cell Line B reaching 4x its peak fed-batch VCD.  At the end of the perfusion stage, the cultures were split into high seed fed-batch production cultures.  Cell Line A's high seed production tracked the performance of its low seed process.  Perfusion N-1 enabled Cell Line B's high seed production to reach 2x the VCD of its low seed process.

Increasing antibody volumetric productivity using perfusion seed cultures

245th National Meeting (2013)

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