(438d) The Effect of High Dissolved Co2 on Cell Growth and Productivity in Bioreactors

A critical concern during scale-up of cell culture processes is the accumulation of dissolved carbon dioxide. Small changes in bioreactor configuration can impact the efficiency of carbon dioxide removal, resulting in up to 2-3 times higher CO2 accumulation after a 10X increase in reactor scale. High CO2 levels in cell culture have been linked to significant decreases in culture productivity and changes in product quality profiles for recombinant monoclonal antibodies. In this presentation, we propose an approach for the evaluation of the risk and impact of CO2 accumulation during process scale-up. The CO2 profile in the large-scale reactor is estimated, using a comprehensive mathematical model which accounts for reactor geometry, process control, and variable CO2 removal strategies. The process is then run in a series of scale-down model reactors at the estimated carbon dioxide levels. Based on the results, a CO2 removal strategy and a maximum allowable CO2 level are selected. Using this model for a monoclonal antibody process, we demonstrated that a pCO2 level of 250 mm Hg could be tolerated in a large-scale reactor without any impact to product quality or specific productivity.