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Evaluation of criteria for bioreactor comparison and operation standardization for mammalian cell culture
Authors:Oscar Platas Barradas  Uwe Jandt  Linh Da Minh Phan  Mario E Villanueva  Martin Schaletzky  Alexander Rath  Susann Freund  Udo Reichl  Eva Skerhutt  Sebastian Scholz  Thomas Noll  Volker Sandig  Ralf Pörtner  An‐Ping Zeng
Institution:1. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, , Hamburg, Germany;2. Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, , Magdeburg, Germany;3. Cell Culture Technology, Bielefeld University, , Bielefeld, Germany;4. Chief Scientific Officer, ProBioGen AG, , Berlin, Germany
Abstract:Development of bioprocesses with mammalian cell culture deals with different bioreactor types and scales. The bioreactors might be intended for generation of cell inoculum and production, research, process development, validation, or transfer purposes. During these activities, not only the difficulty of up and downscaling might lead to failure of consistency in cell growth, but also the use of different bioreactor geometries and operation conditions. In such cases, criteria for bioreactor design and process transfer should be carefully evaluated in order to select appropriate cultivation parameters. In this work, power input, mixing time, impeller tip speed, and Reynolds number have been compared systematically for the cultivation of the human cell line AGE1.HN within three partner laboratories using five different bioreactor systems. Proper operation ranges for the bioreactors were identified using the maximal cell‐specific growth rate (μmax) as indicator. Common optimum values for process transfer criteria were found in these geometrically different bioreactors, in which deviations of μmax between cultivation systems can be importantly reduced. The data obtained in this work are used for process standardization and comparability of results obtained in different bioreactor systems, i.e. to guarantee lab‐to‐lab consistency for systems biology approaches using mammalian cells.
Keywords:Bioreactor geometry  Comparison criteria  Mammalian cell culture  Process standardization  Process transfer
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