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Novel spiking methods developed for anion exchange chromatography operating in continuous processing
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  • Ying Li,
  • Audrey Chang,
  • David Beattie,
  • Kathryn Remington
Ying Li
MilliporeSigma Process Solutions Research and Development
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Audrey Chang
MilliporeSigma
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David Beattie
MilliporeSigma Process Solutions Research and Development
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Kathryn Remington
MilliporeSigma Process Solutions Services
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Abstract

Many manufacturers of biopharmaceuticals are moving from batch to continuous processing. While this approach offers advantages over batch processing to manufacturers, demonstration of viral clearance for continuous processes is more complex. Regulators expect manufacturers to use an appropriate scale down model, based on solid scientific justification, to verify the viral reduction capacity of the manufacturing process. The output from chromatography columns operated in continuous processes fluctuates in concentration so that the load for the subsequent column is not homogenous. This must be considered when designing viral clearance studies. One way to approach clearance studies is to downscale the continuous process, using multi-column chromatography systems and in-line spiking of virus. The multi-column chromatography systems and experienced operators, however, may not be available at the CRO performing the study. Another approach is to evaluate each step in traditional batch mode, using existing chromatography systems, but to modify the spiking and loading conditions to mimic the variance introduced by the transition between the two connected process steps. Using a standard chromatography system, we have evaluated a flow through anion exchange chromatography step in a monoclonal antibody process using five different methods to introduce the virus to the column. We have shown that regardless of whether the virus spike is introduced in a well-mixed batch mode, introduced as a concentrated pulse of virus with homogeneous mAb or with a concentrated peak of mAb, the clearance of MMV was similar. This study introduces an alternative way to evaluate viral clearance in a continuous process.

Peer review status:ACCEPTED

02 Jan 2020Submitted to Biotechnology and Bioengineering
03 Jan 2020Submission Checks Completed
03 Jan 2020Assigned to Editor
06 Jan 2020Reviewer(s) Assigned
03 Feb 2020Review(s) Completed, Editorial Evaluation Pending
03 Feb 2020Editorial Decision: Revise Major
03 Apr 20201st Revision Received
04 Apr 2020Submission Checks Completed
04 Apr 2020Assigned to Editor
13 Jul 2020Review(s) Completed, Editorial Evaluation Pending
13 Jul 2020Editorial Decision: Accept