A systematic mass-transfer modeling approach for mammalian cell culture bioreactor scale-up

A mathematical mass-transfer model was developed based on the mass balance of gas exchange in cell culture bioreactors. The model combines the bioreactor mass transfer properties and mammalian cell metabolic parameters to predict the cell culture process oxygen demands and carbon dioxide accumulation in bioreactors. With the guidance of the mass-transfer model, a CHO cell culture process to produce a therapeutic antibody was successfully scaled up from 2-L to 1500-L bioreactor directly without intermediate steps. The process performances and product quality attributes demonstrate good robustness and consistency between small and large scales. This mass-transfer model provides a more systematic and reliable approach for mammalian cell culture bioreactor scaling up.