In recent years, mammalian cell culture processes have transitioned from the use of complex culture media containing various animal, plant, or yeast derived components, to chemically-defined (CD) formulations with an intent to improve process robustness and product consistency, both key requirements of commercial cell culture processes. However, studies from our laboratory have shown that use of CD media does not necessarily ensure product consistency as the quality and variability associated with some components can significantly impact cell culture performance and critical quality attributes (CQAs) of the product. Consequently, rigorous screening and qualification of CD media are essential to ensure consistent cell culture process performance. However, performing these studies in bioreactors is both time-consuming and resource-intensive. To overcome these limitations, we have used 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 derived from several medium formulations and vendors were evaluated using this HT method. While no significant differences in cell culture performance were observed, product quality was impacted in some medium lots. Comprehensive chemical analyses identified differences in some organic and inorganic components across these medium lots which were associated with product quality changes. In addition, results from the HT studies were also confirmed in 2 L bioreactor studies validating the utility of this approach. The simplicity of this new approach should enable rapid screening of cell culture media resulting in more robust and reproducible cell culture processes.<br/> <br/>

Elucidating raw material variability in mammalian cell cultures using high throughput small-scale models

251st National Meeting (2016)

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