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The authors give an overview of scaling approaches and present good scaling practices for the biopharma industry.
Cell culture process transfer requires a good understanding of the physicochemical conditions within a bioreactor. This includes the hydrodynamic environment induced by the agitator and the mass transfer capability of the spargers at different gas flow rates. Cell culture processes need to operate in a design space where the oxygen supply and carbon dioxide removal can match cellular metabolism. In addition, prohibitive high shear stress and high gas flow rates can create bubble damage or foaming issues and should be avoided. Identifying the boundaries of a design space for a robust process is difficult due to the extensive characterization data needed and the diversity of single use bioreactor design. The authors show that in-silico models can be used to determine ranges in the design space for agitation and gas flow rates that fulfill the requirements of oxygen transfer and carbon dioxide stripping. Furthermore, the design space can be explored by locking one or two input variables and using the model to calculate acceptable ranges for the remaining parameters. With this methodology, it is possible to navigate the design space, understand correlations of the operating parameters in silico, and build understanding about the limits for all operating parameters.
Submitted: July 5, 2023
Accepted: Nov. 16, 2023
William Tran is a senior scientist, Jack Bowers is a senior principal scientist, and T. Craig Seamans is a senior principal scientist; all at Biologics Process R&D, Merck and Co. (MSD outside of the United States and Canada). Helena Öhrvik is senior product manager, and Andreas Castan is strategic technology leader; both at In Silico Process Development, Cytiva.
Volume 37, No. 1
When referring to this article, please cite it as Tran, W.; Bowers, J.; Seamans, T. C.; Öhrvik, H.; Castan, A. Right the First Time: Bioreactor Scale and Design Translation. BioPharm International 2024, 37 (1), 26–30,33.