Scale-up considerations for monoclonal antibody production process: an oxygen transfer flux approach

Abstract

Background When scaling up a monoclonal antibody (mAb) production process in stirred tank bioreactor, oxygen transfer is probably one of the most challenging parameters to consider. Approaches such as keeping constant specific power input or tip speed across the scales are widely described in the literature and are often based on the assumption that mammalian cells are sensitive to shear stress. However, with the high cell densities reached in modern processes, such scale-up strategies can lead to relatively high gas flow rate to compensate low agitation speed which could be detrimental to cells in its own right. As an alternative, we explored a scale-up strategy based on the overall oxygen transfer flux (OTF) required by the cell culture process. OTF was defined as directly proportional to oxygen transfer coefficient (kLa) and oxygen enrichment in the gas mix. This way the overall gas flow can be kept at relatively low values, while satisfying the oxygen requirements of a high cell density culture.