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Online Monitoring and Control of Upstream Cell Culture Process Using 1D & 2D-LC with SegFlow Interface
  • +15
  • Letha Chemmalil,
  • Dhanuka Wasalthanthri,
  • Xin Zhang,
  • June Kuang,
  • Chun Shao,
  • Robin Barbour,
  • Sohil Bhavsar,
  • Tanushree Prabhakar,
  • Ryan Knihtila,
  • Jay West,
  • Neha Puri,
  • Kyle McHugh,
  • Matthew Rehmann,
  • Qin He,
  • Jianlin Xu,
  • Michael Borys,
  • Julia Ding,
  • Zheng Jian Li
Letha Chemmalil
Bristol-Myers Squibb Co
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Dhanuka Wasalthanthri
Bristol-Myers Squibb Co
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Xin Zhang
Bristol-Myers Squibb Co
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June Kuang
Bristol-Myers Squibb Co
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Chun Shao
Bristol-Myers Squibb Co
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Robin Barbour
University of Rochester
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Sohil Bhavsar
Bristol-Myers Squibb Co
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Tanushree Prabhakar
Bristol-Myers Squibb Co
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Ryan Knihtila
Dragonfly Therapeutics
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Jay West
Bristol-Myers Squibb Co
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Neha Puri
Bristol-Myers Squibb Co
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Kyle McHugh
Bristol-Myers Squibb Co
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Matthew Rehmann
Bristol-Myers Squibb
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Qin He
Bristol-Myers Squibb
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Jianlin Xu
Bristol-Myers Squibb Company
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Michael Borys
Bristol-Myers Squibb Company
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Julia Ding
Bristol-Myers Squibb Co
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Zheng Jian Li
Bristol-Myers Squibb Company
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Abstract

The biopharmaceutical industry is transitioning from currently deployed batch-mode bioprocessing to a highly efficient and agile next generation bioprocessing with the adaptation of continuous bioprocessing, which reduces the capital investment and operational costs. Continuous bioprocessing, aligned with FDA’s quality-by-design (QbD) platform, is designed to develop robust processes to deliver safe and effective drugs. With the deployment of knowledge based operations, product quality can be built into the process to achieve desired critical quality attributes (CQAs) with reduced variability. To facilitate next generation continuous bio-processing, it is essential to embrace a fundamental shift-in-paradigm from “quality-by-testing” to “quality-by-design”, which requires the deployment of process analytical technologies (PAT). With the adaptation of PAT, a systematic approach of process and product understanding and timely process control are feasible. Deployment of PAT tools for real-time monitoring of CQAs and feedback control is critical for continuous bioprocessing. Given the current deficiency in PAT tools to support continuous bioprocessing, we have integrated Agilent 2D-LC with a post-flow-splitter in conjunction with the SegFlow automated sampler to the bioreactors. With this integrated system, we have established a platform for online measurements of titer and CQAs of monoclonal antibodies (mAbs) as well as amino acid concentrations of bioreactor cell culture.

Peer review status:ACCEPTED

24 Dec 2020Submitted to Biotechnology and Bioengineering
31 Dec 2020Submission Checks Completed
31 Dec 2020Assigned to Editor
04 Jan 2021Reviewer(s) Assigned
19 Feb 2021Editorial Decision: Revise Minor
19 Feb 2021Review(s) Completed, Editorial Evaluation Pending
03 Apr 20211st Revision Received
08 Apr 2021Submission Checks Completed
08 Apr 2021Assigned to Editor
13 May 2021Reviewer(s) Assigned
14 Jun 2021Review(s) Completed, Editorial Evaluation Pending
14 Jun 2021Editorial Decision: Accept