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An integrated continuous downstream process with real-time control: A case study with periodic countercurrent chromatography and continuous virus inactivation
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO. Department of Chemical Engineering, Lund University, Lund, Sweden.ORCID iD: 0000-0002-8592-4207
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO. Department of Chemical Engineering, Lund University, Lund, Sweden.ORCID iD: 0000-0003-3568-7706
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2021 (English)In: Biotechnology and Bioengineering, ISSN 0006-3592, E-ISSN 1097-0290, Vol. 118, no 4, p. 1645-1657Article in journal (Refereed) Published
Abstract [en]

Integrated continuous downstream processes with process analytical technology offer a promising opportunity to reduce production costs and increase process flexibility and adaptability. In this case study, an integrated continuous process was used to purify a recombinant protein on laboratory scale in a two-system setup that can be used as a general downstream setup offering multiproduct and multipurpose manufacturing capabilities. The process consisted of continuous solvent/detergent virus inactivation followed by periodic countercurrent chromatography in the capture step, and a final chromatographic polishing step. A real-time controller was implemented to ensure stable operation by adapting the downstream process to external changes. A concentration disturbance was introduced to test the controller. After the disturbance was applied, the product output recovered within 6 h, showing the effectiveness of the controller. In a comparison of the process with and without the controller, the product output per cycle increased by 27%, the resin utilization increased from 71.4% to 87.9%, and the specific buffer consumption was decreased by 21% with the controller, while maintaining a similar yield and purity as in the process without the disturbance. In addition, the integrated continuous process outperformed the batch process, increasing the productivity by 95% and the yield by 28%.

Place, publisher, year, edition, pages
Wiley , 2021. Vol. 118, no 4, p. 1645-1657
Keywords [en]
continuous virus inactivation, integrated continuous downstream, periodic countercurrent chromatography, process analytical technology, real-time control, Batch data processing, Controllers, Liquid chromatography, Real time control, Recombinant proteins, Viruses, Continuous process, Downstream process, Manufacturing capability, Periodic counter-current chromatographies, Process flexibility, Real time controllers, Virus inactivation, Process control, buffer, detergent, recombinant protein, resin, solvent, Article, batch process, clinical effectiveness, counter current chromatography, downstream processing, nonhuman, productivity
National Category
Control Engineering
Identifiers
URN: urn:nbn:se:kth:diva-304935DOI: 10.1002/bit.27681ISI: 000614431500001PubMedID: 33459355Scopus ID: 2-s2.0-85100335177OAI: oai:DiVA.org:kth-304935DiVA, id: diva2:1612818
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QC 20211119

Available from: 2021-11-19 Created: 2021-11-19 Last updated: 2023-12-14Bibliographically approved

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Gomis-Fons, Joaquin

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Gomis-Fons, JoaquinNilsson, Bernt
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