Mammalian cell culture continues to be the workhorse for expression of high value recombinant therapeutic protein modalities. As the requirements for the manufacturing process performance, product quality and safety continue to become more stringent, mammalian cell shear during clarification operation has become a critical consideration in preventing product quality degradation and in purification train design. Shearing of the cells during centrifugation and depth filtration exposes the complex therapeutic products to intracellular enzymes, such as the reductases and proteases. Additionally, cell breakage dumps difficult-to-remove proteins, such as lipases, into the process fluid. Cell shear in the primary clarification stage also produces an insoluble fragment “tail” that interferes with membranes, capture chromatography, and polishing train performance. While cell shear can be attenuated by a proper depth filter selection and running the primary clarification stage in a “true chromatography mode”, this approach is not very robust due to the non-chromatographic nature of depth filtration media and variability of cell size depending on cell line and on culturing strategy.<br/>Here we present a novel harvesting approach that utilizes chromatographically defined AEX non-woven bed that is capable of capturing cells and cell fragments using charge. Chromatographic approach to clarification enables capture of insoluble particles at very low pressures and is equally effective over  very wide range of particle sizes. The result is that cell shear can be very precisely controlled and minimized to background level regardless of cell line, cell density, or cell culture conditions. Furthermore, since the clarification media is chromatographically defined, the system is highly reproducible and scalable from high-throughput screening, to manufacturing scale. This enables one to accelerate process development from discovery to commercial deployment.<br/>

Overcoming cell shear in mAb harvests using novel harvesting technology

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.