Authors: Benjamin Neunstoecklin Thomas K Villiger Eric Lucas Matthieu Stettler Hervé Broly Massimo Morbidelli Miroslav Soos
Publish Date: 2015/12/05
Volume: 100, Issue: 8, Pages: 3489-3498
Abstract
Although several scaling bioreactor models of mammalian cell cultures are suggested and described in the literature they mostly lack a significant validation at pilot or manufacturing scale The aim of this study is to validate an oscillating hydrodynamic stress loop system developed earlier by our group for the evaluation of the maximum operating range for stirring based on a maximum tolerable hydrodynamic stress A 300L pilotscale bioreactor for cultivation of a Sp2/0 cell line was used for this purpose Prior to cultivations a stresssensitive particulate system was applied to determine the stress values generated by stirring and sparging Pilotscale data collected from 7 to 28Pa maximum stress conditions were compared with data from classical 3L cultivations and cultivations from the oscillating stress loop system Results for the growth behavior analyzed metabolites productivity and product quality showed a dependency on the different environmental stress conditions but not on reactor size Pilotscale conditions were very similar to those generated in the oscillating stress loop model confirming its predictive capability including conditions at the edge of failure
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