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Beyond heuristics: CFD‐based novel multiparameter scale‐up for geometrically disparate bioreactors demonstrated at industrial 2kL–10kL scales
Author(s) -
Scully James,
Considine Laura B.,
Smith Mark T.,
McAlea Eamonn,
Jones Nephi,
O'Connell Edel,
Madsen Emilee,
Power Martin,
Mellors Philip,
Crowley John,
O'Leary Niall,
Carver Scott,
Van Plew Daniel
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27323
Subject(s) - computational fluid dynamics , bioreactor , scalability , scale (ratio) , computer science , scale up , biochemical engineering , residence time (fluid dynamics) , heuristics , scaling , process engineering , process (computing) , microscale chemistry , mechanics , engineering , mathematics , chemistry , physics , organic chemistry , classical mechanics , quantum mechanics , operating system , geometry , geotechnical engineering , mathematics education , database
The timely delivery of the most up‐to‐date medicines and drug products is essential for patients throughout the world. Successful scaling of the bioreactors used within the biopharmaceutical industry plays a large part in the quality and time to market of these products. Scale and topology differences between vessels add a large degree of complication and uncertainty within the scaling process. Currently, this approach is primarily achieved through extensive experimentation and facile empirical correlations, which can be costly and time consuming while providing limited information. The work undertaken in the current study demonstrates a more robust and complete approach using computational fluid dynamics (CFD) to provide potent multiparameter scalability, which only requires geometric and material properties before a comprehensive and detailed solution can be generated. The CFD model output parameters that can be applied in the scale‐up include mass transfer rates, mixing times, shear rates, gas hold‐up values, and bubble residence times. The authors examined three bioreactors with variable geometries and were able to validate them based on single‐phase and multiphase experiments. Furthermore, leveraging the resulting CFD output information enabled the authors to successfully scale‐up from a known 2kL to a novel and disparate 5kL single‐use bioreactor in the first attempted cell culture. This multiparameter scaling approach promises to ultimately lead to a reduction in the time to market providing patients with earlier access to the most groundbreaking medicines.