Root Cause and Prevention of Monoclonal Antibody Disulfide Bonds Reduction During Biopharmaceutical Manufacturing Process

doi:10.13523/j.cb.2201016

China Biotechnology

2022, Vol. 42

Issue (6): 66-75 DOI: 10.13523/j.cb.2201016

Root Cause and Prevention of Monoclonal Antibody Disulfide Bonds Reduction During Biopharmaceutical Manufacturing Process

ZHANG Xin-di¹,FAN Chang-wei²,SONG Xiao-qing^2,^*(

),XU Cui-yun²,HUANG Feng-jie¹

1. College of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
2. Shanghai Henlius Biotech, Inc., Shanghai 200233, China

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Abstract

Monoclonal antibody disulfide bonds reduction has been a common issue in biopharmaceutical process, which could produce low-molecular weight fragments, affect product quality, and lead to decreased protein purity and stability. Moreover, it could also affect the safety and effectiveness of drugs. Antibody disulfide bonds reduction is a reversible redox reaction caused by intracellular thioredoxin system and glutathione system, and is related to the specific production process. In recent years, with the development of antibody drugs and mammalian cell culture scale, disulfide bonds reduction is observed more frequently. To solve this problem, scientists have been constantly developing mitigation strategies to ensure the product quality. In this paper, the antibody disulfide bonds structure, cause of disulfide bonds reduction and influencing factors in manufacturing process were summarized. It is focused on the prevention methods in the manufacturing process. Additionally, several feasible process analysis techniques are listed so as to provide reference for the further development of monoclonal antibody drugs in manufacturing.

Key words： Antibody Disulfide bond Oxidation and reduction Process development Process analytical technology

Received: 14 January 2022 Published: 07 July 2022

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Corresponding Authors: Xiao-qing SONG E-mail: hfj@cpu.edu.cn

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	Feng-jie HUANG

Cite this article:

ZHANG Xin-di,FAN Chang-wei,SONG Xiao-qing,XU Cui-yun,HUANG Feng-jie. Root Cause and Prevention of Monoclonal Antibody Disulfide Bonds Reduction During Biopharmaceutical Manufacturing Process. China Biotechnology, 2022, 42(6): 66-75.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2201016 OR https://manu60.magtech.com.cn/biotech/Y2022/V42/I6/66

Fig.1 Disulfide bond structure and reduced form of antibody(a) Intrachain and interchain disulfide bonds in intact IgG (b) Five forms of reduced antibody VH: heavy chain variable region; CH₁, CH₂, CH₃: heavy chain constant region; VL: light chain variable region; CL: light chain constant region

Fig.2 Mechanism of thioredoxin system and glutathione system reducing disulfide bond of antibody

Table 1 Different approaches to prevent disulfide bond reduction and rescue reduced antibody during manufacturing process


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