Progression of continuous downstream processing of monoclonal antibodies: Current trends and challenges

2018/08/07 by Balaji Somasundaram, Kristina Pleitt, Evan Shave +3 · 122 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Engineering · Medicine · #Biochemical engineering #Bottleneck #Chemistry #Computer science #Downstream (manufacturing) #Downstream processing #Embedded system #Engineering #Flexibility (engineering) #Manufacturing engineering #Modular design #Monoclonal and Polyclonal Antibodies Research #Operations management #Process (computing) #Process engineering #Protein purification and stability #Upstream (networking) #Upstream and downstream (DNA) #Viral Infectious Diseases and Gene Expression in Insects

paper · doi:10.1002/bit.26812

published in Biotechnology and Bioengineering 115(12), 2893-2907 (Wiley)

openalex publication_date 2018/08/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27

Abstract

Rapid advances in intensifying upstream processes for biologics production have left downstream processing as a bottleneck in the manufacturing scheme. Biomanufacturers are pursuing continuous downstream process development to increase efficiency and flexibility, reduce footprint and cost of goods, and improve product consistency and quality. Even after successful laboratory trials, the implementation of a continuous process at manufacturing scale is not easy to achieve. This paper reviews specific challenges in converting each downstream unit operation to a continuous mode. Key elements of developing practical strategies for overcoming these challenges are detailed. These include equipment valve complexity, favorable column aspect ratio, protein-A resin selection, quantitative assessment of chromatogram peak size and shape, holistic process characterization approach, and a customized process economic evaluation. Overall, this study provides a comprehensive review of current trends and the path forward for implementing continuous downstream processing at the manufacturing scale.

Citations

• Continuous downstream processing for high value biological products: A Review

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