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Beneficial effects of pyruvate for a high-density perfusion process
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  • Stefania Caso,
  • Mathieu Aeby,
  • Martin Jordan,
  • Raphael Guillot,
  • Jean-Marc Bielser
Stefania Caso
Merck Serono SA

Corresponding Author:[email protected]

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Mathieu Aeby
Merck Serono SA
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Martin Jordan
Merck Serono SA
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Raphael Guillot
Merck Serono SA
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Jean-Marc Bielser
Merck Serono SA
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High volumetric productivities can be achieved when perfusion processes are operated at high cell densities. Yet it is fairly challenging to keep high cell density cultures in a steady state over an extended period. Aiming for robust processes, in this study cultures were operated at a constant biomass specific perfusion rate (BSPR). The cell density was monitored with a capacitance probe and a continuous bleed maintained the cell density at the targeted viable cell volume (VCV). Despite our tightly controlled BSPR, a gradual accumulation of ammonium and changes in cell diameter were observed during the production phase for the three different monoclonal antibodies (mAbs). Although a lot of efforts in media optimization have been made to reduce ammonium in fed-batch process, less examples are known about how media components impact the cellular metabolism and thus the quality of monoclonal antibodies in continuous processes. In this work, we show that a continuous Na-pyruvate fed at 2 g/L/day strongly reduced ammonium production and stabilized fucosylation, sialylation and high mannose content for three different mAbs.
26 Oct 2021Submitted to Biotechnology and Bioengineering
26 Oct 2021Submission Checks Completed
26 Oct 2021Assigned to Editor
10 Nov 2021Reviewer(s) Assigned
06 Dec 2021Review(s) Completed, Editorial Evaluation Pending
06 Dec 2021Editorial Decision: Revise Minor
20 Dec 20211st Revision Received
21 Dec 2021Submission Checks Completed
21 Dec 2021Assigned to Editor
23 Dec 2021Reviewer(s) Assigned
24 Dec 2021Review(s) Completed, Editorial Evaluation Pending
24 Dec 2021Editorial Decision: Accept