Regenerative perfusion bioreactor for biologics production with lower COGs.

Abstract

Perfusion bioreactor systems enable intensified bioprocessing with high cell densities and volumetric productivities in monoclonal antibody (mAb) manufacturing. However, their widespread adoption remains constrained by the high consumption of chemically defined cell culture media. In this study, we introduce a multi-stage electrokinetic waste separation process that regenerates spent media, recovering up to 87.5% of the spent-medium volume for reuse. Using a mock-perfusion model, the regeneration-recycle processes were shown to sustain high-density Chinese hamster ovary cell growth, compared with spent media recycling without regeneration. Integration into a self-recycling perfusion bioreactor (350 mL working volume) operating with 75% regenerated media sustained the target viable cell density and antibody titer, with limited reductions to cell-specific growth rate (~31%) and cell-specific productivity (~9%), supporting the feasibility of high-ratio media recycling. Techno-economic modeling of large-scale scenarios revealed that media regeneration could offer a path to $15/g COGs, thereby increasing the accessibility of mAbs. Techno-economic modeling of hypothetical large-scale manufacturing scenarios indicated that the experimentally demonstrated process could reduce cost of goods (COG) by approximately 9%, and identified a theoretical pathway toward ~$15/g COG contingent upon multi-cycle regeneration processes that could be developed in the future. These results support regenerative perfusion as a promising process-intensification strategy that, with further development, may be adaptable to other mammalian cell culture platforms where media cost and sustainability are critical bottlenecks.