Practical Considerations for the Scale-Up of Chinese Hamster Ovary (CHO) Cell Cultures

Monoclonal antibodies (mAbs), which are most commonly produced through the use of Chinese Hamster Ovary (CHO) cells in large-scale bioreactors, remain the fastest-growing segment of the global biopharmaceutical market. During process development, scale-up is done stepwise from micro-bioreactors or shake flasks, to benchtop bioreactors, passing by pilot-scale platforms before finally being implemented in industrial-scale vessels. However, achieving seamless scale-up between these production volumes is a non-trivial task. Operating parameters must be selected in order to ensure proper gas transfer, a homogeneous culture volume, minimal hydrodynamic stress applied to cells, and ultimately result in comparable cell culture performances across scales. Mixing and aeration parameters are generally recognized as being the predominant factors affecting culture performance during scale-up. Constant volumetric power input (P/V), constant oxygen mass transfer coefficient (kLa), constant gas flow rate per unit volume (vvm) and constant impeller tip speed are among the most frequently used criteria when performing culture scale-up, but they all have implications and inherent limitations that must be taken into account. The use of computational fluid dynamics (CFD) and carefully designed scale-down models can assist in that endeavour and help reduce the time and costs associated with bioreactor scale-up.