Performance of mammalian cell culture processes contribute significantly towards the overall success in production and economics of biologics such as recombinant monoclonal antibodies (mAbs) and next generation recombinant proteins. Rapid and effective clinical entry is still a rate limiting item for prospective biopharmaceuticals to enter clinical testing. Chinese hamster ovary (CHO)-based cell culture processes conventionally include cell line generation, media and feed optimization, and process design optimization to increase the productivity and establish acceptable product quality outputs for production of recombinant proteins. This process is complex, time consuming and resource intensive. Significant efforts are ongoing in this area to develop cell culture platforms that combine new state-of the-art technologies for genetic vector design, medium optimization and process design optimization to reduce the overall timeline. At KBI, we have made significant advances in developing cell culture processes that enable high productivity (&gt; 5 g/L in a 14 day fed-batch culture) and meet precise product quality requirements. This has been achieved via implementation of high expression platforms and high-throughput process development workflows that combine to deliver high productivity processes very fast for clinical production. The platform approach includes use of optimally designed proprietary expression vectors (SUREtech vectors that bear Selexis Genetic Elements), high-throughput screening of clones from different rounds of single cell cloning and screening of process conditions using established scale down model miniaturized bioreactors. This is followed by DoE-based experiments to optimize process parameters for high-titer and precise product quality processes. The workflow allows for easy scale up to clinical and commercial scales. We present development of a platform cell culture process for a mAb which was eventually applied to six different mAbs for generation of clinical material at 200 - 2000L scales. The platform allows to produce biopharmaceuticals and support Investigational new drug (IND) application in approximately 9 months after gene synthesis. This approach has been successfully demonstrated at KBI and utilized for over 12 recombinant proteins including the 6 mAbs discussed in this presentation.

Robust platform cell culture processes utilizing the Selexis expression system for decreasing process development timelines and enhancing speed to clinic

255th National Meeting (2018)

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