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

Autor: Agostinetto R; MerckSerono S.p.A, Guidonia di Montecello, Italy., Rossi M; MerckSerono S.p.A, Guidonia di Montecello, Italy., Dawson J; EMD Serono, Billerica, Massachusetts, USA., Lim A; EMD Serono, Billerica, Massachusetts, USA., Simoneau MH; Ares Trading SA/Merck SA Switzerland, Aubonne, Switzerland., Boucher C; Ares Trading SA/Merck SA Switzerland, Aubonne, Switzerland., Valldorf B; Merck KGaA, Darmstadt, Germany., Ross-Gillespie A; Ares Trading SA/Merck SA Switzerland, Aubonne, Switzerland., Jardine JG; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.; IAVI, New York, New York, USA.; IAVI, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA., Sok D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.; IAVI, New York, New York, USA.; IAVI, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.; IAVI, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA., Hassell T; IAVI, New York, New York, USA., Broly H; Ares Trading SA/Merck SA Switzerland, Aubonne, Switzerland., Palinsky W; Ares Trading SA/Merck SA Switzerland, Aubonne, Switzerland., Dupraz P; Ares Trading SA/Merck SA Switzerland, Aubonne, Switzerland., Feinberg M; IAVI, New York, New York, USA., Dey AK; IAVI, New York, New York, USA.
Jazyk: angličtina
Zdroj: Biotechnology and bioengineering [Biotechnol Bioeng] 2022 Feb; Vol. 119 (2), pp. 663-666. Date of Electronic Publication: 2021 Dec 10.
DOI: 10.1002/bit.27995
Abstrakt: 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.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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