A new version of proprietary Chinese hamster ovary cell culture media was recently developed at Eli Lilly and Company for the production of biopharmaceuticals. It was observed that increasing the osmolality of the media improved the viability of cells at the end of the production stage, and for some cell lines, higher end viability contributed to an increase in titer. Osmolality was increased by addition of sodium chloride to the basal medium. Shake flask and bioreactor studies identified that high osmolality media could impact not only cell growth but also product quality in some cell lines. In a particular cell line, the additional NaCl caused high levels of product aggregation measured by size exclusion chromatography. A number of replacements for NaCl were explored to maintain the benefits of increased end viability without forming high levels of product aggregation. Ferric ammonium citrate and lower initial temperature were two replacements which increased end viability similarly to NaCl, without largely increasing aggregate. This work provided levers which can be used for future molecules which may exhibit this novel response to higher levels of NaCl in the basal medium.

Impact of high osmolality cell culture media on cell growth and product quality of biopharmaceuticals

253rd National Meeting (2017)

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