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Realization of Digital Twin for Dynamic Control Toward Sample Variation of Ion Exchange Chromatography in Antibody Separation

Shi, Ce, Chen, Xu‐Jun, Zhong, Xue‐Zhao, Yang, Yan, Lin, Dong‐Qiang, Chen, Ran·2024·Biotechnology and Bioengineering
DOI 10.1002/bit.28660
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Abstract

Digital twin (DT) is a virtual and digital representation of physical objects or processes. In this paper, this concept is applied to dynamic control of the collection window in the ion exchange chromatography (IEC) toward sample variations. A possible structure of a feedforward model‐based control DT system was proposed. Initially, a precise IEC mechanistic model was established through experiments, model fitting, and validation. The average root mean square error (RMSE) of fitting and validation was 8.1% and 7.4%, respectively. Then a model‐based gradient optimization was performed, resulting in a 70.0% yield with a remarkable 11.2% increase. Subsequently, the DT was established by systematically integrating the model, chromatography system, online high‐performance liquid chromatography, and a server computer. The DT was validated under varying load conditions. The results demonstrated that the DT could offer an accurate control with acidic variants proportion and yield difference of less than 2% compared to the offline analysis. The embedding mechanistic model also showed a positive predictive performance with an average RMSE of 11.7% during the DT test under >10% sample variation. Practical scenario tests indicated that tightening the control target could further enhance the DT robustness, achieving over 98% success rate with an average yield of 72.7%. The results demonstrated that the constructed DT could accurately mimic real‐world situations and perform an automated and flexible pooling in IEC. Additionally, a detailed methodology for applying DT was summarized.

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  • Digital twins have been recently constructed for IEX processes, systematically integrated with the HPLC system and a server computer; the DT predicted elution profiles, enabling automated collection control.

    “For instance, DTs have been recently constructed for ion‐exchange chromatography (IEX) processes, and are systematically integrated with the HPLC system and a server computer. The DT was able to predict the elution profiles, enabling automated collection control [114].”

    From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [114]

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Cited by

Sorted by citations

Authors
Shi, C., Chen, X., Zhong, X., Yang, Y., Lin, D., & Chen, R.
Affiliations
  • Process Development Downstream, Shanghai Engineering Research Center of Anti‐tumor Biological Drugs Shanghai Henlius Biotech, Inc. Shanghai China
  • Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering Zhejiang University Hangzhou China
ORCID
Venue
Biotechnology and Bioengineering
Publisher
Wiley
Published
2024-01-17
Volume
121
Issue
5
Pages
1702-1715
ISSN
  • 0006-3592
  • 1097-0290
DOI
10.1002/bit.28660
Cited by
13
References
0
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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