(70a) Disc Stack Centrifugation 2L To 20,000L Scale-Up Evaluation For Mammalian Cell Clarification: Optimization Of Bioreactor Harvest Conditions For Combined Cell Removal And Mab Purification Capabilities

Previous work has demonstrated the control of fermentation harvest broth buffer conditions during the production of therapeutic proteins to assist in cell and contaminant removal using tangential-flow clarification systems. However, there is limited understanding of the effects of harvest conditions on clarification performance using centrifugation and the effects of feed conditions at various centrifuge scales.

We will present a framework for describing the performance of disc-stack centrifugation systems for mammalian cell and impurity removal using controlled harvest conditions. In combination, data from bench/pilot-scale (2L-200L) to large-scale (20,000L) operations will be presented evaluating the impact of controlled parameters on clarification performance.

Settling experiments of unclarified harvest media were performed at various buffer conditions with turbidity, product titer, and impurity assays performed on the supernatant in order to establish optimal harvest feed conditions prior to clarification. Pilot-scale centrifugation studies were then performed at a wide-range of centrifuge flowrates and RPMs using optimized harvest from various clinical products producing IgGs. Large-scale centrifuge runs were also performed under scaled-up conditions set by Lab/Pilot equipment. The data showed a general reduction in centrate clarity compared to clarifying with unadjusted harvest streams at all scales, with improved Post-Centrifuge filtration capacity and impurity removal. Overall, this analysis allows for improved future design and optimization of large-scale Centrifugal operations for processing mammalian cell culture broths.