Rapid cGMP manufacturing of COVID‐19 monoclonal antibody using stable CHO cell pools

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 inev...

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Bibliographic Details
Published in:Biotechnology and bioengineering 2022-02, Vol.119 (2), p.663-666
Main Authors: Agostinetto, Rita, Rossi, Mara, Dawson, Jessica, Lim, Angela, Simoneau, Mirva H., Boucher, Cyril, Valldorf, Bernhard, Ross‐Gillespie, Adin, Jardine, Joseph G., Sok, Devin, Burton, Dennis R., Hassell, Thomas, Broly, Hervé, Palinsky, Wolf, Dupraz, Philippe, Feinberg, Mark, Dey, Antu K.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - biosynthesis
Antibodies, Monoclonal - immunology
Antibodies, Viral - biosynthesis
Antibodies, Viral - immunology
Cell culture
Cell lines
cGMP manufacturing
CHO Cells
CHO pools
Clinical trials
Clinical Trials, Phase I as Topic - methods
Clinical Trials, Phase I as Topic - standards
Communication
Coronaviruses
COVID-19
COVID-19 - immunology
Cricetulus
Cyclic GMP
Drug development
Manufacturing
Manufacturing industry
Monoclonal antibodies
monoclonal antibody
Pandemics
Safety
SARS-CoV-2 - immunology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Transposase
Transposases
Viral diseases
Viral Load
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Summary: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 coronavirus disease 2019 (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‐severe acute respiratory syndrome coronavirus 2 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 preclinical 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 clinical trial material within 4.5 months, in comparison to 12–14 months for production of clinical trial material via the conventional approach. Use of well‐characterized nonclonal stable CHO cell pools and platform processes can expediate cGMP manufacturing of monoclonal antibodies for early clinical development during pandemic outbreaks of emerging infectious diseases.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.27995