Characterization Of Oxygen Mass Transfer Rate (KLa) Using A Statistical Design Of Experiment (DoE) For Bioreactor Scale-Up

Abstract

Bioreactor production development and optimization are typically performed at a small scale to reduce their cost and time requirement. Bioreactor production is scaled-up often based on keeping volumetric mass transfer coefficient (kLa) constant. To facilitate a successful transfer of an optimized small-scale cell culture bioreactor production to lab, pilot, and industrial scale, the kLa profiles for these bioreactors should be determined. Although a number of correlations and predictive models for kLa are available, they do not have universal applicability. The purpose of this study was to use a statistical Design of Experiments (DoE) approach to characterize kLa in 3L, 7L, and 50L bioreactors, and hence to use this information for bioreactor scale-up. Dissolved oxygen sensors were used to measure dissolved oxygen concentrations in the bioreactors. kLa was determined by using the dynamic reoxygenation method. Response surface design of experiment was used to characterize kLa in the bioreactors. Agitation, air flow rate, and volume were included in the experimental design as input parameters, and kLa was used as the output parameter. Results of these studies is discussed in this presentation. The correlations determined here will be used as a tool for bioreactor production development, scale up and tech transfer.

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