The ability to express recombinant antibodies from CHO cells has advanced through developments in cell line selection methods, clone screening, and media formulation. The high oxygen demand of current high performing in-house cell lines was leading to cell culture performance that did not match across the various scales used for cell culture development work. These differences became evident when comparing historical 3 L bioreactor process development studies against runs performed at manufacturing scale (&gt;500 L). Differences in cell culture performance were also evident during the use of cell culture models with volumes at the mL scale, such as spin tubes and multi-well plates, which were utilized for media screening applications. These differences in growth, titer, and PQ across scale signaled that changes needed to be implemented to the scale-down model to create a more efficient and automated system with results that better match manufacturing scale. This model would also be capable of growing alongside industry advancements in cell culture performance, for example, be applied to the development of continuous bioprocessing strategies.<br/>Development work began at the 3L scale, testing impeller configurations and dissolved oxygen control strategies that demonstrate alignment of cell culture performance characteristics with manufacturing scale. Under these strategies, parameters, such as total gas flow, dissolved carbon dioxide, and titer, better matched across scales. Work supporting the spin tube as a high-throughput small scale cell culture model will also be presented. Agitation speed, working volume, and system configuration were the parameters under evaluation with this new approach. The correct balance had to be reached that provided for the necessary aeration of the high oxygen demand cell lines without cell damage and reduced performance generated by high agitation conditions. Automated work streams for the spin tube sampling, assay sample preparation, and feed media additions were developed for integration with this cell culture model. Through automation at this scale, the development team will be empowered to increase experimental throughput. Improvement of scale-down models at the 3L and mL scale that can support high performance cell lines will lead to more efficient cell culture development plans that can be easily implemented at the manufacturing scale.

Improvements To CHO cell culture scale-down model across multiple scales

255th National Meeting (2018)

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