Mammalian cell culture continues to be the workhorse for expression of high value recombinant therapeutic protein modalities. The first step in the recombinant biotherapeutic process is harvesting cell culture fluid containing the product. Conventional approaches for performing this unit operation utilize a combination of depth filtration, centrifugation, and membrane filtration. These technologies utilize differences in density and in size as the principles of separation. As cell culture processes are intensified to yield higher cell densities and product titers, the ability to effectively harvest the cell culture fluid with the consistency and scalability required becomes challenging.<br/><br/>Here we present a novel single stage harvesting approach that utilizes synthetic fibrous anion exchange (AEX) chromatography to efficiently separate the cells, cell debris, and DNA by charge from the harvested cell culture fluid containing the target biotherapeutic product. Precision quaternary ammonium (Q) functionalized polypropylene fiber bed and a 0.2 μm polyether sulfone membrane in a capsule enables a single stage clarification process of low to high-density cell culture with high recovery, and high fidelity of soluble and insoluble contaminant separation. This new clarification approach enables &gt;95% mAb product recoveries, consistent cell loading capacity, and predictable clarification from discovery to commercial manufacturing scale. Furthermore, open structured fibrous media enables low pressure operation with minimal cell shear.

Principles of CHO cell culture harvesting using novel synthetic fiber chromatography

ACS Fall 2021

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