The current bioprocessing landscape has relied on the development of nutrient-rich media and selection of high producing cell lines to drive titers higher and increase drug substance output in a manufacturing facility. In BMS, efforts in upstream process intensification have incorporated perfusion seed bioreactors, to reduce the duration of seed expansion, enable the implementation of a rolling seed and the inoculation of production bioreactors at high cell densities.<br/>This presentation demonstrate the utility of biomass capacitance probes to monitor online cell densities and control perfusion rate in the seed bioreactor. Based on a robust, linear correlation of biomass capacitance to viable cell densities across multiple platform cell lines, the online capacitance data was utilized to dynamically change the media exchange rate to maintain a constant cell-specific perfusion rate (CSPR). A dynamic adjustment of perfusion rate based on online VCD can reduce media utilization rates in large-scale manufacturing. CSPR rates was shown to impact cell growth in perfusion culture and the duration of the N-1 seed. Due to higher seeding densities in fed-batch process, the feed media components and feeding strategy was also adjusted to target a stoichiometric based feeding, where cultures were fed based on growth and nutrient consumption rates estimated from integrated viable cells. This presentation will highlight the impact on process titer yields and product quality profile using this intensified, high density fed batch process.

Process improvement of a high density fed-batch process using N-1 perfusion seed cultures

255th National Meeting (2018)

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