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Rapid cGMP Manufacturing of COVID-19 monoclonal antibody using stable CHO cell pools
  • +13
  • Rita Agostinetto,
  • Jessica Dawson,
  • Angela Lim,
  • Mirva Hejjaoui-simoneau,
  • Cyril Boucher,
  • Bernhard Valldorf,
  • Adin Ross-gillespie,
  • Joseph Jardine,
  • Devin Sok,
  • Dennis Burton,
  • Thomas Hassell ,
  • Hervé Broly,
  • Wolf Palinsky,
  • Philippe Dupraz,
  • Mark Feinberg,
  • Antu Dey
Rita Agostinetto
Merck Serono SpA
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Jessica Dawson
EMD Serono Biotech Center Inc
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Angela Lim
EMD Serono Biotech Center Inc
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Mirva Hejjaoui-simoneau
Ares Trading SA
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Cyril Boucher
Ares Trading SA
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Bernhard Valldorf
Merck KGaA
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Adin Ross-gillespie
Ares Trading SA
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Joseph Jardine
The Scripps Research Institute
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Devin Sok
The Scripps Research Institute
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Dennis Burton
The Scripps Research Institute
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Thomas Hassell
International Aids Vaccine Initiative
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Hervé Broly
Merck Serono SA-Corsier-sur-Vevey
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Wolf Palinsky
Ares Trading SA
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Philippe Dupraz
Ares Trading SA
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Mark Feinberg
International Aids Vaccine Initiative
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Antu Dey
Greenlight Biosciences Inc
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Abstract

Therapeutic proteins, including monoclonal antibodies, are typically manufactured using clonally-derived, stable host cell lines, since consistent and predictable cell culture performance is highly desirable. However, selecting and preparing banks of stable clones takes considerable time, which inevitably extends overall development timelines for new therapeutics by delaying the start of subsequent activities, such as the scale-up of manufacturing processes. In the context of the COVID-19 pandemic, with its intense pressure for accelerated development strategies, we used a novel transposon-based Leap-In Transposase® system to rapidly generate high-titer stable pools and then used them directly for large scale-manufacturing of an anti-SARS-CoV2 monoclonal antibody under cGMP. We performed the safety testing of our non-clonal cell bank, then used it to produce material at a 200L-scale for pre-clinical safety studies and formulation development work, and thereafter at 2000L scale for supply of material for a Phase 1 clinical trial. Testing demonstrated the comparability of critical product qualities between the two scales and, more importantly, that our final clinical trial product met all pre-set product quality specifications. The above expediated approach provided clinically-ready material within 4.5 months, in comparison to 12-14 months for production of clinical trial material via the conventional approach.
10 Aug 2021Submitted to Biotechnology and Bioengineering
11 Aug 2021Submission Checks Completed
11 Aug 2021Assigned to Editor
23 Aug 2021Reviewer(s) Assigned
09 Sep 2021Review(s) Completed, Editorial Evaluation Pending
09 Sep 2021Editorial Decision: Revise Major
12 Oct 20211st Revision Received
09 Nov 2021Submission Checks Completed
09 Nov 2021Assigned to Editor
10 Nov 2021Reviewer(s) Assigned
13 Nov 2021Review(s) Completed, Editorial Evaluation Pending
13 Nov 2021Editorial Decision: Accept
Feb 2022Published in Biotechnology and Bioengineering volume 119 issue 2 on pages 663-666. 10.1002/bit.27995