There is growing interest in the development of integrated continuous bioprocesses for the production of important biotherapeutics due to the potential for enhanced productivity, greater flexibility, and improved product quality.  The transition from batch to continuous bioprocessing requires a major re-thinking of the downstream purification process, creating exciting new opportunities for membrane technology. This talk will focus on the use of continuous countercurrent staged membrane systems for initial product capture and for final formulation. Continuous Countercurrent Tangential Chromatography (CCTC) provides truly continuous steady-state product capture and purification using a column-free system in which the chromatographic operations are conducted on a flowing slurry using hollow fiber membranes to control the resin flow. Results using a Protein A affinity resin show high levels of host cell protein removal from a monoclonal antibody product, with the countercurrent staged providing significantly greater throughput with improved product yield and purification. A similar approach can be used for continuous selective precipitation of monoclonal antibodies, completely eliminating the high cost of the affinity resin. Countercurrent staged diafiltration has been developed as a new strategy for providing high levels of buffer exchange in a single-pass continuous format.  These examples highlight how one can adapt membrane systems to continuous bioprocessing, providing exciting opportunities for improved manufacturing of high-value biopharmaceuticals.

Learning Objectives:

1. Explain the benefits of implementing continuous bioprocessing.

2. Identify the opportunities for using countercurrent staging to enhance the performance of downstream processes.