Continuous downstream processing for high value biological products: A Review

2015/07/07 by Andrew L. Zydney · 299 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Engineering · Mathematics · Medicine · #Biochemical engineering #Bioprocess #Bioreactor #Chemistry #Chromatography #Computer science #Continuous production #Downstream (manufacturing) #Downstream processing #Engineering #Environmental science #Manufacturing engineering #Mathematics #Monoclonal and Polyclonal Antibodies Research #Operations management #Process (computing) #Process analytical technology #Process development #Process engineering #Product (mathematics) #Protein purification and stability #Unit operation #Viral Infectious Diseases and Gene Expression in Insects

paper · pdf · doi:10.1002/bit.25695

published in Biotechnology and Bioengineering 113(3), 465-475 (Wiley)

openalex publication_date 2015/07/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25

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.

Citations

• Chromatographic separation of three monoclonal antibody variants using multicolumn countercurrent solvent gradient purification (MCSGP)

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