Do you run continuous downstream too? How do you connect your upstream and downstream?
This question is part of the following Ask The Expert session:
Implementation of Continuous Manufacturing Strategies for Protein Therapeutics
Company: WuXi Biologics
Job Title: Vice President, Cell Culture Process Development
Yes. There are various advantages to continuous downstream manufacture. It can be implemented together with continuous upstream to realize an integrated continuous process. For fed-batch culture, continuous downstream allows lower one-time resin expense due to use of smaller sized columns and higher resin utilization efficiency. The critical technologies that allow for continuous downstream processing are multi-column chromatography systems and single-pass Tangential Flow Filtration (TFF). Although full continuous processing is the ultimate goal, the most cost-effective application is to develop a continuous product capture step. We have successfully established continuous product capture using a multi-column chromatography system at bench-top scale and it is also working on the scaled-up process.
The connection between continuous upstream and downstream is quite straight forward if hollow fiber-based cell separation systems are used for perfusion cell culture and harvest – otherwise, additional clarification steps are required. Single-pass TFF can be used as an option to concentrate perfusion cell culture harvests before the product capture step if titers are too low. And intermediate storage or break tanks can be used as optional steps to ensure operational robustness.