Monitoring online biomass with a capacitance sensor during scale-up of industrially relevant CHO cell culture fed-batch processes in single-use bioreactors

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Metze, S.; Ruhl, S.; Greller, G.; Grimm, C.; Scholz, J.: Monitoring online biomass with a capacitance sensor during scale-up of industrially relevant CHO cell culture fed-batch processes in single-use bioreactors. In: Bioprocess and Biosystems Engineering 43 (2020), Nr. 2, S. 193-205. DOI: https://doi.org/10.1007/s00449-019-02216-4

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Zum Zitieren der Version im Repositorium verwenden Sie bitte diesen DOI: https://doi.org/10.15488/10626

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In 2004, the FDA published a guideline to implement process analytical technologies (PAT) in biopharmaceutical processes for process monitoring to gain process understanding and for the control of important process parameters. Viable cell concentration (VCC) is one of the most important key performance indicator (KPI) during mammalian cell cultivation processes. Commonly, this is measured offline. In this work, we demonstrated the comparability and scalability of linear regression models derived from online capacitance measurements. The linear regressions were used to predict the VCC and other familiar offline biomass indicators, like the viable cell volume (VCV) and the wet cell weight (WCW), in two different industrially relevant CHO cell culture processes (Process A and Process B). Therefore, different single-use bioreactor scales (50–2000 L) were used to prove feasibility and scalability of the in-line sensor integration. Coefficient of determinations of 0.79 for Process A and 0.99 for Process B for the WCW were achieved. The VCV was described with high coefficients of determination of 0.96 (Process A) and 0.98 (Process B), respectively. In agreement with other work from the literature, the VCC was only described within the exponential growth phase, but resulting in excellent coefficients of determination of 0.99 (Process A) and 0.96 (Process B), respectively. Monitoring these KPIs online using linear regression models appeared to be scale-independent, enabled deeper process understanding (e.g. here demonstrated in monitoring, the feeding profile) and showed the potential of this method for process control. © 2019, The Author(s).
Lizenzbestimmungen: CC BY 4.0 Unported
Publikationstyp: Article
Publikationsstatus: publishedVersion
Erstveröffentlichung: 2020
Die Publikation erscheint in Sammlung(en):Naturwissenschaftliche Fakultät

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