The purpose of the harvest step in a monoclonal antibody downstream purification process is to remove biomass, particulates, and other suspended material from the cell culture broth to generate a product stream suitable for purification by liquid chromatography. Removing biomass and other particulates eases the burden on the capture column and extends its lifetime. A traditional harvest process employs a two-step approach using centrifugation combined with depth filtration. In this process, coarse solids and intact cells are first removed using a centrifuge, and the resulting centrate is further clarified by depth and membrane filtration in series. Direct filtration has the potential of greatly simplifying the overall harvest process by directly loading the harvest material on high-capacity depth filters and consequently removing the need for additional preparative steps such as centrifugation or flocculation. In this poster, we highlight process development strategies for direct filtration harvests that can increase the filter loading capacity, particularly with regard to high cell density feed streams (&gt; 40 million cells/mL). Filter loading and facility fits were informed by metrics such as the depth filter volumetric capacity for solids and filtrate turbidity. Different types of depth filters, a wide range of fluxes and depth filter ratios, as well as different types of sterile membrane filters were explored to ensure a robust operation and scalability. The strategies discussed here can aid in transforming a trial-and-error development approach to one that is more methodological and predictive. The strategy for tech transfer including facility fit will also be discussed.<br/>

Process development strategies for high cell density monoclonal antibody harvest

ACS Fall 2020 Virtual Meeting

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