(476f) Effect of Hydrodynamic Forces On CHO Cells Used Under Industrial Production Conditions

Authors: 
Scott, W. H., University of Birmingham
Kiss, R., Genentech, Inc.
Meier, S., Genentech, Inc.
Amaah, A., Genentech Inc.
Nienow, A., Birmingham University


The effect of hydrodynamic forces on CHO cells used for the production of biopharmaceuticals has been studied by multiple academic and industrial researchers. Such studies have included evaluation of lethal forces, as well as non-lethal forces, for their effect(s) on cell growth and productivity as well as recombinant protein quality attributes. In this work, two different CHO production cell lines were studied in a repetitive defined elongational shear field device, utilizing two types of pumping systems (peristaltic and syringe pumps). Results to date show that the peristaltic pumping action required to drive the flow through the shear device causes more damage than the shear device itself at low flow rates. Growth and productivity are affected, but not protein quality. Syringe pumps, on the other hand, do not appear to show any significant adverse effects under the flow rates studied. Energy dissipation rates through the shear device are compared to a variety of energy dissipation rates in stirred tank bioreactors, the typical production vessel for industrial purposes. Practically high energy dissipation rates in bioreactors do not show any adverse effects on performance or protein quality with one cell line, consistent with previous results showing no significant effects on growth or productivity with multiple cell lines. This work will be summarized in the context of practical conditions in typical stirred tank bioreactors, and the likelihood that such hydrodynamic forces would significantly impact process performance or protein quality attributes.

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