Despite demonstration of clonal origin of cell lines, the mutations rates in CHO cells with increasing age in culture result in genetic diversity. Investigation of generational stability to fulfill regulatory expectations adds significant timelines to cell line development, which may bottleneck expedited workflows. We have established a comprehensive methodology to minimize relative instability of top clones identified for process development and establishment of a robust manufacturing process. The procedure for selecting a top clone includes tracking maintenance of rank order from static to shaken stages during cell line development, using standardized methods for cloning, development of culture medium sensitive for appropriate selection pressure, mapping flow cytometry-based diversity in subpopulations, and implementation of cell culture fed batch conditions. The fed-batch bioreactor study performed using a platform cell culture process is used to assess manufacturability and product quality. Clone performance is tested in a seed train followed by production in ambr15 or ambr250 bioreactors. A clone ranking system using weighted rank orders has been developed and successfully utilized for multiple cell lines. Outputs from this study are measured in a quantitative and qualitative approach and will be described. This integrated strategy for clone selection provides the basis for determining the top candidate clone while allowing for flexibility with different cell line types, molecule types and product filing status.

Clone ranking methodology for expedited process development using parallel workflows

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.