(511b) Process Improvement of Tangential Flow Filtration Harvest of a Monoclonal Antibody From NS0 Cell Culture: A Case Study

Tangential flow filtration (TFF) is often used in biotech industry for cell clarification and monoclonal antibody recovery from mammalian cell culture. We have optimized a TFF platform process for the harvest of a monoclonal antibody from NS0 fed-batch cell culture, resulting in an improvement from 65% to 98% in step yield. In this study, a scale down TFF system was developed at 2 L scale. A key observation during the process was that trans-membrane pressure drop changed from positive to negative along the length of the fiber, which could possibly result in a reversed flow of antibody from filtrate to retentate. It was hypothesized that reducing the pressure drop along the fiber and eliminating the reversed filtrate flow might improve the process yield and filter efficiency. Several process parameters including fiber diameter, recirculation flow rate, filtrate flow rate, and fiber length were studied using the scale down model to optimize the filtration process. Experimental condition using hollow fiber membrane with a larger inner diameter (1.0 vs. 0.6 mm in diameter) was able to improve the recovery yield from 65 to 77%. Reducing the recirculation rate by 5-fold from 400 to 80 ml/min improved the process yield to 92%. Increased filtrate flow rate from 8 to 14 ml/min was able to reduce the processing time from 5 to 3 hours. The optimal condition combining the larger fiber diameter, slower recirculation rate and faster filtrate rate resulted in nearly full recovery (98%) of antibody within a short processing time. This case study provides a better understanding of TFF process and is applicable to the large scale TFF harvest of antibody production process.