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Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants

Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care. A wealth of informati...

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Autores principales: Beck, Alain, Nowak, Christine, Meshulam, Deborah, Reynolds, Kristina, Chen, David, Pacardo, Dennis B., Nicholls, Samantha B., Carven, Gregory J., Gu, Zhenyu, Fang, Jing, Wang, Dongdong, Katiyar, Amit, Xiang, Tao, Liu, Hongcheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703962/
https://www.ncbi.nlm.nih.gov/pubmed/36412839
http://dx.doi.org/10.3390/antib11040073
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author Beck, Alain
Nowak, Christine
Meshulam, Deborah
Reynolds, Kristina
Chen, David
Pacardo, Dennis B.
Nicholls, Samantha B.
Carven, Gregory J.
Gu, Zhenyu
Fang, Jing
Wang, Dongdong
Katiyar, Amit
Xiang, Tao
Liu, Hongcheng
author_facet Beck, Alain
Nowak, Christine
Meshulam, Deborah
Reynolds, Kristina
Chen, David
Pacardo, Dennis B.
Nicholls, Samantha B.
Carven, Gregory J.
Gu, Zhenyu
Fang, Jing
Wang, Dongdong
Katiyar, Amit
Xiang, Tao
Liu, Hongcheng
author_sort Beck, Alain
collection PubMed
description Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care. A wealth of information about mAbs regarding their structure, stability, post-translation modifications, and the relationship between modification and function has been reported. Yet, substantial resources are still required throughout development and commercialization to have appropriate control strategies to maintain consistent product quality, safety, and efficacy. A typical feature of mAbs is charge heterogeneity, which stems from a variety of modifications, including modifications that are common to many mAbs or unique to a specific molecule or process. Charge heterogeneity is highly sensitive to process changes and thus a good indicator of a robust process. It is a high-risk quality attribute that could potentially fail the specification and comparability required for batch disposition. Failure to meet product specifications or comparability can substantially affect clinical development timelines. To mitigate these risks, the general rule is to maintain a comparable charge profile when process changes are inevitably introduced during development and even after commercialization. Otherwise, new peaks or varied levels of acidic and basic species must be justified based on scientific knowledge and clinical experience for a specific molecule. Here, we summarize the current understanding of mAb charge variants and outline risk-based control strategies to support process development and ultimately commercialization.
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spelling pubmed-97039622022-11-29 Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants Beck, Alain Nowak, Christine Meshulam, Deborah Reynolds, Kristina Chen, David Pacardo, Dennis B. Nicholls, Samantha B. Carven, Gregory J. Gu, Zhenyu Fang, Jing Wang, Dongdong Katiyar, Amit Xiang, Tao Liu, Hongcheng Antibodies (Basel) Review Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care. A wealth of information about mAbs regarding their structure, stability, post-translation modifications, and the relationship between modification and function has been reported. Yet, substantial resources are still required throughout development and commercialization to have appropriate control strategies to maintain consistent product quality, safety, and efficacy. A typical feature of mAbs is charge heterogeneity, which stems from a variety of modifications, including modifications that are common to many mAbs or unique to a specific molecule or process. Charge heterogeneity is highly sensitive to process changes and thus a good indicator of a robust process. It is a high-risk quality attribute that could potentially fail the specification and comparability required for batch disposition. Failure to meet product specifications or comparability can substantially affect clinical development timelines. To mitigate these risks, the general rule is to maintain a comparable charge profile when process changes are inevitably introduced during development and even after commercialization. Otherwise, new peaks or varied levels of acidic and basic species must be justified based on scientific knowledge and clinical experience for a specific molecule. Here, we summarize the current understanding of mAb charge variants and outline risk-based control strategies to support process development and ultimately commercialization. MDPI 2022-11-20 /pmc/articles/PMC9703962/ /pubmed/36412839 http://dx.doi.org/10.3390/antib11040073 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Beck, Alain
Nowak, Christine
Meshulam, Deborah
Reynolds, Kristina
Chen, David
Pacardo, Dennis B.
Nicholls, Samantha B.
Carven, Gregory J.
Gu, Zhenyu
Fang, Jing
Wang, Dongdong
Katiyar, Amit
Xiang, Tao
Liu, Hongcheng
Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants
title Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants
title_full Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants
title_fullStr Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants
title_full_unstemmed Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants
title_short Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants
title_sort risk-based control strategies of recombinant monoclonal antibody charge variants
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703962/
https://www.ncbi.nlm.nih.gov/pubmed/36412839
http://dx.doi.org/10.3390/antib11040073
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