Continuous downstream processing for high value biological products: A Review

• Published in: Biotechnology and bioengineering Vol. 113; no. 3; pp. 465 - 475
• Main Author: Zydney, Andrew L.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2016
• Subjects: Bioengineering; Biological; Biological Products - isolation & purification; Biological Products - metabolism; Bioprocessing; Bioreactors; bioseparations; Biotechnology - methods; Chromatography; continuous processes; Design for recycling; downstream processing; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Reduction; Separation; simulated moving bed; bioseparations; bioprocessing; continuous processes; downstream processing; chromatography; simulated moving bed
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.25695

ABSTRACT There is growing interest in the possibility of developing truly continuous processes for the large‐scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi‐product manufacturing facilities. This paper reviews the current state‐of‐the‐art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. Biotechnol. Bioeng. 2016;113: 465–475. © 2015 Wiley Periodicals, Inc. There is growing interetst in the use of integrated continuous processes for biopharmaceutical production. This review focuses on available technologies for continuous downstream operations, including continuous options for high resolution chromatographic separations.