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Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305

High-producing cell line could improve the affordability and availability of biotherapeutic products. A post-approval production cell line change, low-titer CHO-K1S to high-titer CHO-K1SV GS-KO, was performed for a China marketed bevacizumab biosimilar IBI305. Currently, there is no regulatory guide...

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Autores principales: Wu, Zhouyi, Xu, Gangling, He, Wu, Yu, Chuanfei, Huang, Wanqiu, Zheng, Shirui, Kang, Dian, Xie, Michael H, Cao, Xingjun, Wang, Lan, Wei, Kaikun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481892/
https://www.ncbi.nlm.nih.gov/pubmed/37680352
http://dx.doi.org/10.1093/abt/tbad017
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author Wu, Zhouyi
Xu, Gangling
He, Wu
Yu, Chuanfei
Huang, Wanqiu
Zheng, Shirui
Kang, Dian
Xie, Michael H
Cao, Xingjun
Wang, Lan
Wei, Kaikun
author_facet Wu, Zhouyi
Xu, Gangling
He, Wu
Yu, Chuanfei
Huang, Wanqiu
Zheng, Shirui
Kang, Dian
Xie, Michael H
Cao, Xingjun
Wang, Lan
Wei, Kaikun
author_sort Wu, Zhouyi
collection PubMed
description High-producing cell line could improve the affordability and availability of biotherapeutic products. A post-approval production cell line change, low-titer CHO-K1S to high-titer CHO-K1SV GS-KO, was performed for a China marketed bevacizumab biosimilar IBI305. Currently, there is no regulatory guideline specifically addressing the requirements for comparability study of post-approval cell line change, which is generally regarded as the most complex process change for biological products. Following the quality by design principle and risk assessment, an extensive analytical characterization and three-way comparison was performed by using a panel of advanced analytical methods. Orthogonal and state-of-the-art techniques including nuclear magnetic resonance and high-resolution mass spectrometry were applied to mitigate the potential uncertainties of higher-order structures and to exclude any new sequence variants, scrambled disulfide bonds, glycan moiety and undesired process-related impurities such as host cell proteins. Nonclinical and clinical pharmacokinetics (PK) studies were conducted subsequently to further confirm the comparability. The results demonstrated that the post-change IBI305 was analytically comparable to the pre-change one and similar to the reference product in physicochemical and biological properties, as well as the degradation behaviors in accelerated stability and forced degradation studies. The comparability was further confirmed by comparable PK, pharmacodynamics, toxicological and immunogenicity profiles of nonclinical and clinical studies. The comparability strategy presented here might extend to cell line changes of other post-approval biological products, and particularly set a precedent in China for post-approval cell line change of commercialized biosimilars.
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spelling pubmed-104818922023-09-07 Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305 Wu, Zhouyi Xu, Gangling He, Wu Yu, Chuanfei Huang, Wanqiu Zheng, Shirui Kang, Dian Xie, Michael H Cao, Xingjun Wang, Lan Wei, Kaikun Antib Ther Research Article High-producing cell line could improve the affordability and availability of biotherapeutic products. A post-approval production cell line change, low-titer CHO-K1S to high-titer CHO-K1SV GS-KO, was performed for a China marketed bevacizumab biosimilar IBI305. Currently, there is no regulatory guideline specifically addressing the requirements for comparability study of post-approval cell line change, which is generally regarded as the most complex process change for biological products. Following the quality by design principle and risk assessment, an extensive analytical characterization and three-way comparison was performed by using a panel of advanced analytical methods. Orthogonal and state-of-the-art techniques including nuclear magnetic resonance and high-resolution mass spectrometry were applied to mitigate the potential uncertainties of higher-order structures and to exclude any new sequence variants, scrambled disulfide bonds, glycan moiety and undesired process-related impurities such as host cell proteins. Nonclinical and clinical pharmacokinetics (PK) studies were conducted subsequently to further confirm the comparability. The results demonstrated that the post-change IBI305 was analytically comparable to the pre-change one and similar to the reference product in physicochemical and biological properties, as well as the degradation behaviors in accelerated stability and forced degradation studies. The comparability was further confirmed by comparable PK, pharmacodynamics, toxicological and immunogenicity profiles of nonclinical and clinical studies. The comparability strategy presented here might extend to cell line changes of other post-approval biological products, and particularly set a precedent in China for post-approval cell line change of commercialized biosimilars. Oxford University Press 2023-08-04 /pmc/articles/PMC10481892/ /pubmed/37680352 http://dx.doi.org/10.1093/abt/tbad017 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Wu, Zhouyi
Xu, Gangling
He, Wu
Yu, Chuanfei
Huang, Wanqiu
Zheng, Shirui
Kang, Dian
Xie, Michael H
Cao, Xingjun
Wang, Lan
Wei, Kaikun
Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305
title Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305
title_full Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305
title_fullStr Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305
title_full_unstemmed Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305
title_short Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305
title_sort comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar ibi305
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481892/
https://www.ncbi.nlm.nih.gov/pubmed/37680352
http://dx.doi.org/10.1093/abt/tbad017
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