In recent years, advances in cell line engineering and cell culture media design have allowed for improvements in monoclonal antibody expression with cell culture systems exhibiting product titers greater than 10 g/L. Although optimized cell lines and improved media compositions have helped increase cell productivity, high product titers are still often associated with cell densities exceeding 20 × 106 cells/mL. These high-density cell cultures pose a great challenge using existing solid-liquid separation techniques, because of the need to remove larger amounts of biomass and the increase in submicron particles. In addition, the higher levels of soluble impurities introduce new bottlenecks for chromatographic processing, because of the increased levels of contaminants from cell debris generated during cell culture and harvesting.
Clarisolve® depth filter with pDADMAC flocculant pretreatment demonstrates a significant improvement in filtration efficiency, including a reduction in supernatant turbidity and improved volumetric throughput compared to conventional filters. The purification process removes the residual polymer to a concentration less than 1 ppm, where it showed no in vitro cytotoxicity and hemolytic concerns, and could be used as a reasonable target for acceptable polymer clearance. Overall, pDADMAC treatment in combination with Clarisolve® depth filters provides an effective solution for harvesting high-cell-density cultures and can be easily incorporated into current clarification platforms.