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Viral clearance in end-to-end continuous process for mAb purification: Total flow-through integrated polishing on two columns connected to virus filtration
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  • Hironobu Shirataki,
  • Yoshihiro Matsumoto,
  • Fuminori Konoike,
  • Shuichi Yamamoto
Hironobu Shirataki
Asahi Kasei Medical Kabushiki Kaisha

Corresponding Author:[email protected]

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Yoshihiro Matsumoto
JNC Kabushiki Kaisha Yokohama Kenkyujo
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Fuminori Konoike
Kabushiki Kaisha Kaneka Takasago Kenkyujo
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Shuichi Yamamoto
Yamaguchi Daigaku Kogakubu
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Abstract

There are few reports of the adoption of continuous processes in bioproduction, particularly the implementation of end-to-end continuous processes, due to difficulties such as feed adjustment, production batch demarcation, and incorporating virus filtration. Here, we propose an end-to-end continuous process for a monoclonal antibody (mAb) with three integrated process segments: upstream production processes with pool-less direct connection, pooled low pH virus inactivation with automated pH control and a total flow-through integrated polishing process in which two columns were directly connected with a virus filter. The pooled virus inactivation step demarcates the batch, and high impurities reduction and mAb recovery were achieved for batches conducted in succession. Viral clearance tests also confirmed robust virus reduction for the flow-through two column chromatography and the virus filtration steps. Additionally, viral clearance tests with two different hollow fiber virus filters operated at flux ranging from 1.5 to 40 LMH confirmed robust virus reduction over these ranges. Complete clearance with LRV ≥ 4 was achieved even with a process pause at the lowest flux. The end-to-end continuous process proposed in this study is highly applicable to production processes, and the investigated virus filters have excellent applicability to continuous processes conducted at constant flux.
24 Feb 2023Submitted to Biotechnology and Bioengineering
24 Feb 2023Submission Checks Completed
24 Feb 2023Assigned to Editor
24 Feb 2023Review(s) Completed, Editorial Evaluation Pending
04 Mar 2023Reviewer(s) Assigned
19 Apr 2023Editorial Decision: Revise Minor
12 May 20231st Revision Received
15 May 2023Submission Checks Completed
15 May 2023Assigned to Editor
15 May 2023Review(s) Completed, Editorial Evaluation Pending
29 May 2023Editorial Decision: Accept