(552e) Understanding the Effect of High Gas Entrance Velocity on Chinese Hamster Ovary (CHO) Cell Culture Process

Growing demand for biologics requires high intensity unit operations such as high cell density fed-batch processes. High yielding cell culture process requires higher aeration/oxygenation to satisfy high oxygen demand and for carbon dioxide removal in a bioreactor. Higher aeration/oxygenation through sparger can result in higher gas entrance velocity (GEV), which can lead to cellular damage and can adversely impact the cell culture performance. A study was performed to evaluate the effect of high GEV on CHO cell culture process using spargers of different number/size of holes. Our results demonstrate that high GEV imparts significant negative effect on cell growth, viability, and productivity. Similar effects were observed in large scale production bioreactors. In addition, the extent of cell damage (necrosis or apoptosis) under high GEV was examined by lactate dehydrogenase measurement and flow cytometry analysis. Insights into the cell condition under high GEV will be presented and discussed.