单克隆抗体药物序列分析的审评思考

Sequence analysis of therapeutic monoclonal antibody

改造用于重组表达生物技术药物宿主的遗传信息,包括将外源基因转入宿主细胞之后,对其DNA、mRNA和蛋白水平上的序列加以分析是产品/工艺开发和质量研究的重要部分。本文以单克隆抗体药物为例,介绍了近年来新一代测序和液质联用等新技术在序列分析方面的应用。这些技术在成本、耗时和专业能力要求方面各不相同,应按照逐步递进的原则,在药物生命周期的不同阶段合理选择使用,以提高研发的成功率并保证产品质量,进而保证临床使用的疗效和安全性。

Sequence analysis of DNA,mRNA and protein is an essential component of biologics or bioprocess development.Analysis of sequences at the DNA,mRNA,and protein levels after the transfer of the gene of interest into a host cell is an important part of quality control.This article reviews the application of new technologies such as next-generation sequencing and LC-MS/MS in biological drug development such as monoclonal antibodies.These techniques have different requirements in term of cost,handling time and expertise.Selecting an appropriate technique with a sound rationale at different stages of drug development will add to the success rate of research and development,and ensure product quality,thus ensuring the clinical efficacy and safety.