We have previously demonstrated a robust, scalable cell culture process using chemically defined media that is capable of producing high titers.  When this process was applied to a particular antibody program, large variations in metabolism, resulting in dramatically different lactate concentrations, were observed at extended cultivation times.  These metabolic shifts are undesirable as a reproducible process would require a shortened process length and consequently lower titer.  We investigated the causes of the metabolic variability, with a focus on cell-specific lactate production rates.  This metabolic investigation led directly into media optimization experiments.  Specifically organic acids from the tricarboxylic acid cycle, such as citrate and alpha-ketoglutarate, were added to cell culture media.  Cells cultivated in media containing these organic acids exhibit a different metabolic trajectory with a stabilized lactate time course.

Improved process development based on increased understanding of metabolism

245th National Meeting (2013)

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