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Integrated process consisting of column chromatography followed by virus filtration for plasma IgG and mAb purification at constant flow rate: analysis of filtration behavior using clogging models and viral clearance tests
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  • Hironobu Shirataki,
  • Yoshiro Yokoyama,
  • Hiroki Taniguchi,
  • Miku Azeyanagi
Hironobu Shirataki
Asahi Kasei Medical Co Ltd
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Yoshiro Yokoyama
Asahi Kasei Medical Co Ltd Nobeoka Area Okatomi Plant
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Hiroki Taniguchi
Asahi Kasei Medical Co Ltd
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Miku Azeyanagi
Asahi Kasei Medical Co Ltd Nobeoka Area Okatomi Plant
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Abstract

We evaluated filtration behavior and virus removal capability for a mAb and plasma IgG under constant flow rate directly following flow-through column chromatography in an integrated process. For mAb solution with quantified host cell protein (HCP) content processed in flow-through mode on in-series mixed-mode AEX and modified CEX columns connected to the Planova BioEX filter (pool-less), HCP logarithmic reduction value (LRV) of 2.3 and 93.9% protein recovery were achieved for the process. Filtration behavior for 5 to 15 mg/mL plasma IgG run at flux of 10 to 100 LMH to 100 L/m2 throughput on Planova BioEX filters showed similar behavior across the protein concentrations tested although filtration pressure increased with throughput at 50 LMH and above, indicating the suitability of lower flux processes for continuous processing. Comparing both plasma IgG and mAb filtration behavior to four clogging models showed little difference in fit among the models, but with slightly better fit to the cake filtration model. Viral clearance tested by in-line spiking X-MuLV or MVM into purified plasma IgG showed robust removal at low flux. Integrating the Planova BioEX filter into continuous processes with column chromatography can achieve efficient downstream processing with reduced footprint and process time.

Peer review status:ACCEPTED

24 Sep 2020Submitted to Biotechnology and Bioengineering
24 Sep 2020Submission Checks Completed
24 Sep 2020Assigned to Editor
02 Oct 2020Reviewer(s) Assigned
16 Nov 2020Review(s) Completed, Editorial Evaluation Pending
16 Nov 2020Editorial Decision: Revise Major
25 Dec 20201st Revision Received
26 Dec 2020Assigned to Editor
26 Dec 2020Submission Checks Completed
04 Jan 2021Reviewer(s) Assigned
18 Jan 2021Editorial Decision: Revise Minor
18 Jan 2021Review(s) Completed, Editorial Evaluation Pending
07 Feb 20212nd Revision Received
08 Feb 2021Submission Checks Completed
08 Feb 2021Assigned to Editor
19 Feb 2021Reviewer(s) Assigned
18 Mar 2021Review(s) Completed, Editorial Evaluation Pending
18 Mar 2021Editorial Decision: Revise Minor
14 Apr 20213rd Revision Received
14 Apr 2021Submission Checks Completed
14 Apr 2021Assigned to Editor
20 May 2021Review(s) Completed, Editorial Evaluation Pending
20 May 2021Editorial Decision: Accept