Evaluation of Continuous Downstream Processing: Industrial Perspective

The downstream process utilized by Biogen for the purification of monoclonal antibodies (mAb) was developed to deliver purified drug substance and provide acceptable viral safety. The process consists of harvest steps, chromatographic columns, two virus inactivation steps, a viral filtration step, and one or two ultrafiltration steps. This chapter illustrates a schematic of continuous downstream whose feed is harvested cell culture fluid. The annual mass throughput that can be obtained from a given manufacturing facility is dependent on the rate-limiting step and the overall yield of the downstream operations. Downstream operations would impact the throughput only through the yield term. If batch downstream operations are not rate-limiting, then, from a throughput perspective, continuous downstream operation would be beneficial only if it resulted in an increase in the overall yield when compared with standard discrete batch operation.