Abstract
The compatibility of CHO cell culture medium formulations with all stages of the bioprocess must be evaluated through small-scale studies prior to scale-up for commercial manufacturing operations. Here, we describe the development of a bespoke small-scale device for assessing the compatibility of culture media with a widely implemented upstream viral clearance strategy, high-temperature short-time (HTST) treatment. The thermal stability of undefined medium formulations supplemented with soy hydrolysates was evaluated upon variations in critical HTST processing parameters, namely, holding times and temperatures. Prolonged holding times of 43 s at temperatures of 110 °C did not adversely impact medium quality while significant degradation was observed upon treatment at elevated temperatures (200 °C) for shorter time periods (11 s). The performance of the device was benchmarked against a commercially available mini-pilot HTST system upon treatment of identical formulations on both platforms. Processed medium samples were analyzed by untargeted LC-MS/MS for compositional profiling followed by chemometric evaluation, which confirmed the observed degradation effects caused by elevated holding temperatures but revealed comparable performance of our developed device with the commercial mini-pilot setup. The developed device can assist medium optimization activities by reducing volume requirements relative to commercially available mini-pilot instrumentation and by facilitating fast throughput evaluation of heat-induced effects on multiple medium lots.
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Acknowledgements
Special thanks are due to Dr. Karen Twomey and Mr. Donal O’Sullivan from the Tyndall National Institute, Cork, for their assistance with the machining of aluminum blocks.
Funding
This study received funding from Enterprise Ireland under grant number IP/2014/0309, co-funded by the European Union through the European Regional Development Fund (ERDF) 2014-2020 program.
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The authors declare no financial or commercial conflict of interest. Dr. Christian Kaisermayer and Ms. Anna Lindeberg are employees of BioMarin International Limited, Shanbally, Ringaskiddy, Cork, P43 R298, Ireland.
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Floris, P., Curtin, S., Kaisermayer, C. et al. Development of a versatile high-temperature short-time (HTST) pasteurization device for small-scale processing of cell culture medium formulations. Appl Microbiol Biotechnol 102, 5495–5504 (2018). https://doi.org/10.1007/s00253-018-9034-1
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DOI: https://doi.org/10.1007/s00253-018-9034-1