(603t) Development of a Scale-Down Plate Model for Raw Material Variability Analysis in Mammalian Cell Culture

Development of a Scale-down Plate Model for Raw Material Variability

Analysis in Mammalian Cell Culture

Hedieh Rahimi, David Kolwyck, Gary Rogers, Jack Huang and Chetan Goudar (Cell Sciences & Technology, Amgen, Thousand Oaks, CA)

In recent years, cell culture processes in the biopharmaceutical industry have transitioned from complex to chemically-defined (CD) medium with an intent to enhance process robustness and consistency. Despite defined concentrations for all components in a CD medium, recent studies from our laboratory have shown that CD medium use does not ensure process consistency. Specifically, the quality and variability associated with CD medium components can significantly impact cell culture performance and critical quality attributes (CQAs) of the product. Consequently, rigorous selection and qualification of CD medium and reassurance of lot-to-lot consistency are essential for a robust cell culture process. While such studies are typically conducted in bioreactors, they are time and resource intensive which can limit their application. To overcome this limitation, we have developed a high throughput (HT) small-scale plate model to assess the impact of raw material variability on cell culture performance and product quality. Multiple medium powder lots which spanned several medium formulations and vendors were evaluated using the HT plate assay. While no significant differences in cell culture performance were seen, product quality was impacted. Comprehensive chemical analyses identified differences in trace levels of organic and inorganic impurities across medium types which were associated with product quality changes. Additionally, results from the HT plate studies were consistent with those from 2 L bioreactor studies suggesting the utility of this approach to screen variability associated with CD medium. .The simplicity of this new approach should enable rapid screening of cell culture medium resulting in more robust cell culture processes.