抗体药物N-糖表征及质量研究策略探讨

Discussion on Characterization and Quality Control Strategies of Antibody N-Glycosylation

糖基化修饰是抗体药物的关键质量属性(Critical Quality Attributes, CQAs)之一。在现代抗体工业中,调节和控制糖基化修饰对抗体的药代动力学(PK),活性及免疫原性都有着重要影响。作为蛋白质众多翻译后修饰中最为复杂且重要的修饰之一,N-糖的表征和质量控制往往充满挑战。早期研发时,为创新型药物制定高效的N-糖分析策略和为生物类似药制定与原研药的N-糖相似性判定标准是关键的;工业生产时,证明工艺条件变更前后的N-糖质量可比是必要的。本文综述了抗体药物N-糖基化修饰在不同水平上的表征方法,并结合相关法规,对创新型药物和生物类似药在研发阶段和工业生产阶段的N-糖质量研究策略进行了讨论。

Glycosylation is one of the critical quality attributes (CQAs) of antibody drugs. In the modern anti-body industry, the regulation and control of glycosylation has avital impact on the pharmacokinetics (PK), potency and immunogenicity. As one of the most complicate and important modifications among all post-translational modifications (PTMs), the characterization and quality control of N-glycans can be very challenging. In the early stage, it is critically important to develop efficient N-glycan analysis strategies for innovative drugs and establish N-glycan similarity criteria for biosimilar;in the late stage, comparability study of N-glycans is necessary when manufacturing process changed. This article reviews the characterization methods of N-glycosylation of antibody drugs at different levels, and discusses the N-glycan research strategies of innovative drugs and biosimilars in the early and late stages in conjunction with relevant regulations.