Antibody disulfide bond reduction has been a challenge in monoclonal antibody manufacturing. It could lead to decrease of product purity and failure to meet the targeted product profile and/or specifications. More importantly, disulfide bond reduction could also impact drug safety and efficacy. Biopharmaceutical industry has been examining the root causes and developing mitigation strategies to address the challenge. Previous studies have more focused on understanding how manufacturing process could influence disulfide bond reduction, and how to mitigate the disulfide bond reduction during process development. However, there are limited studies on comparing IgG subclass type influences on disulfide bond reduction and evaluating whether the susceptibility of disulfide bond reduction vary within the same IgG subclass, and between different IgG subclasses. To address this limitation, it is critical to develop a systematic evaluation methodology and build an interchain disulfide bond reduction kinetic model for disulfide bond reduction comparison. In this study, we developed a novel approach to evaluate the disulfide bond susceptibility among different molecules. It provides a better control in disulfide bond reduction conditions, enabling the comparison conducted under the same reaction environment. We applied this tool to compare different IgG subclasses and will discuss observed the disulfide bond reduction susceptibility differences among different IgG subclasses. The methodology could be applied as a risk assessment tool in evaluating molecule disulfide bond reduction risk during process development.

Novel approach to evaluate disulfide bond reduction susceptibility among different IgG subclasses

ACS Spring 2022

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