(582af) Rational Approach for the Improvement of Cell Culture Media Based On the Life Cycle Management of An Investigational Product

Early stage upstream process development for mammalian cell culture is focused on generating material at sufficient levels on the most efficient timeline to enable clinical studies.  During this stage, a top-down level development approach may be pursued to improve platform cell culture media through enrichment strategies.  The use of select surfactants enabled highly enriched chemically-defined feed media that led to improved titer performance in a CHO based expression system.  As the product matures through its lifecycle, the focus shifts to building a more complete understanding of the media impact on the process.  At this stage, a bottom-up level approach was pursued to uncover the key media components that resulted in the improved titer performance from the enriched feed.  These studies utilized robotic liquid handling to generate thousands of media variants.  Utilizing a DOE-based approach, these media were tested in a high-throughput fashion in 24 well plates to examine how the CHO cell line responded to changes in media composition.  This strategy not only can lead to an improved feed media addition strategy but can also shed light on process robustness.  Both approaches increased antibody titers in CHO cell lines at g/L levels compared to the original platform feed strategy and enabled a better understanding of product quality control.