宿主细胞残留蛋白质对单克隆抗体药物质量影响及其质量控制  

Effects of Host Cell Residual Proteins on the Quality and Their Quality Control of Monoclonal Antibody

作　　者：刘国芳[1] 刘晓志[1] 高健[1] 王志明[1] LIU Guo-fang;LIU Xiao-zhi;GAO Jian;WANG Zhi-ming(State Key Laboratory of Antibody Research&Development,New Drug Research and Development Company Ltd,North China Pharmaceutical Corporation,Shijiazhuang 050015,China)

机构地区：[1]华北制药集团新药研究开发有限责任公司抗体药物研制国家重点实验室

出　　处：《中国生物工程杂志》2019年第10期105-111,共7页China Biotechnology

基　　金：国家重大新药创制科技重大专项(2017ZX09306010)资助项目

摘　　要：以单克隆抗体药物(monoclonal antibodies,mAbs)为代表的生物制品药物销售在不断扩大,并呈现持续上升势头,mAbs的使用为疾病治疗提供了新策略。随着mAbs使用量增大,对产品质量提出了更高要求,随着宿主细胞表达mAbs水平的不断提高,宿主细胞蛋白(host cell proteins,HCP)含量也随之增加,上下游生产工艺面临不断挑战。HCP所含蛋白质异常复杂,虽然一些HCP可能会被降解,但残留HCP仍会引起药物临床使用中的不良反应,从而影响药物的安全性和有效性。酶联免疫吸附试验(enzyme-linked immunesorbent assays,ELISAs)是目前HCP检测的重要方法之一,ELISAs可以定量检测药物中总HCP含量,但存在局限性。对正在开发的包括LC-MS/MS在内的多种分析方法进行HCP检测,将为药物工艺过程开发和验证提供更多依据。讨论了以CHO(Chinese hamster ovary,中国仓鼠卵巢)细胞系为宿主的mAbs生产中,HCP的质量控制及检测分析方法的研究进展。The sales of biologic drugs represented by monoclonal antibodies(mAbs)are expanding and showing a rising trend.The use of mAbs provides a new strategy for disease treatment.With the increase in the use of mAbs,higher requirements are placed on the quality of the product.As the level of mAbs expressed by the host cells continues to increase,the content of host cell proteins(HCP)also increases,and the upstream and downstream production processes are constantly faced challenge.The protein contained in HCP is extremely complicated.Although some HCP may be degraded,residual HCP may cause adverse reactions in the clinical use of the drug,thereby affecting the safety and effectiveness of the drug.Enzyme-linked immune sorbent assays(ELISAs)are important methods for HCP detection.ELISAs can quantitatively measure total HCP levels in drugs,but there are limitations.HCP testing of various analytical methods,including LC-MS/MS,is under development,which will provide more evidence for drug process development and validation.The advances in quality control and assays for HCP production in the production of mAbs hosted by the CHO(Chinese hamster ovary)cell line were discussed.

关 键 词：单克隆抗体药物 宿主细胞残留蛋白质 质量控制 检测方法 

分 类 号：Q819[生物学—生物工程]