(726d) Downstream Scale-up Evaluation for High-Titer Mammalian-Based Processes: Platform Strategies for Improved Clarification and Purification Throughput

Previous work has demonstrated the control of mammalian cell broth buffer conditions during the production of high-titer therapeutic proteins to assist in clarification by TFF. However, there is limited understanding of the significant beneficial effects of harvest conditions on clarification performance by centrifugation and subsequent downstream chromatographic steps for processing high-titer products.

We will present a framework for describing the performance of disc-stack centrifugation in conjunction with depth filtration and capture column chromatography for cell and impurity removal using controlled harvest conditions. In combination, data from bench/pilot-scale to large-scale operations will be presented evaluating the impact of controlled parameters on downstream performance.

Pilot-scale centrifugation and depth filtration studies were then performed at a wide-range of centrifuge flowrates and RPMs using optimized harvest from various clinical products producing IgGs. The data shows a significant reduction in centrate clarity compared to clarifying with unadjusted harvest streams at all scales, with improved post-centrifuge filtration capacity and capture column eluate purity and clarity. Overall, this analysis allows for improved future design and optimization of large-scale centrifugal operations for processing mammalian cell culture broths.