(683f) Characterization of Rotary Lobe Pump Damage in Large-Scale Cell Culture Perfusion Process

Perfusion bioprocessing is becoming more prevalent for increasing productivity and shortening seed train and bioreactor stages. When implementing the new perfusion platform in N-1 large-scale manufacturing process (3750L), unexpected viability drop was observed at day 1. This was not seen at the bench scale satellite runs using the same culture and medium. Higher turbidity and lactate dehydrogenase (LDH) were in the large-scale bioreactor also confirmed the cells were stressed more significantly. Towards the end of the process, the transmembrane pressure (TMP) increased significantly and fouled the hollow fiber membrane. Several investigations were conducted to understand the potential root cause including bioreactor sparging, hollow fiber filter shear, the piping of skid design and operation of the rotary lobe pump. A quick mitigation is to lower RPM in the rotary lobe pump which immediately reduced the cell damage. A follow up study to utilize a smaller scale of rotary lobe pump in the lab was conducted. RPM, flow rate, differential pressure across the pump were studied to identify the possible mechanism of cell damage. The results suggested that differential pressure across the pump was the primary cause of cell damage. A small-scale robustness model was developed to better predict manufacturing performance and improve the large-scale operation in the future.