创新单抗药物申报临床试验病毒安全性相关监管指南调研与技术考量  

Guidelines investigation and technical considerations of virus safety during investigational new drug application of innovative monoclonal antibody products

作　　者：崔靖 宋丽娜 CUI Jing;SONG Li-na(Center for Drug Evaluation,National Medical Products Administration(CDE,NMPA),Beijing 100022,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100022

出　　处：《药学学报》2021年第8期2308-2314,共7页Acta Pharmaceutica Sinica

摘　　要：随着我国生物制药自主创新能力的不断提高,越来越多的创新型单抗药物申报注册临床试验,同时国外已上市和/或国外开展临床试验的单克隆抗体药物在国内申报注册临床的数量也不断增加。2018年国家药品监督管理局对外发布了《新药Ⅰ期临床试验申请技术指南》(2018年第16号),该指南对创新药申报临床试验阶段药学研究及申报资料提出了相关要求,极大提高了生物创新药的申报质量。但相比美国药品监管机构和欧盟药品监管机构,我国针对创新药申报临床阶段细化的技术指南尚不完善,如生物技术产品申报临床阶段的病毒安全性评价。本文调研了2018~2020年申请人针对创新单抗药物申报临床阶段的一般性技术问题,发现申请人聚焦的问题包括生产终末细胞和/或细胞收获液检定以及病毒去除或灭活验证。同时,审评中也发现由于申请人对国内外技术指南阶段性要求理解的差异,导致申报资料也存在一定差异。结合我国和美国、欧盟药品监管机构病毒安全性相关技术指南的调研并基于技术考量,本文对生产过程中外源病毒因子检测和病毒去除或灭活验证提出个人建议,旨在确保创新单抗药物在申报临床试验阶段的病毒安全性。With the development of antibody manufacturing technology and improvement of new drug research in domestic industry,more innovative monoclonal antibody products submitted investigational new drug(IND)application.At the same time,monoclonal antibody products from abroad which have been approved marketing authorization and/or conducted clinical trials submitted IND applications in China.The National Medical Products Administration(NMPA)issued the"Guideline of Investigational New Drug Application"(No.16,2018)which emphasized the chemical,manufacturing,and control(CMC)regulatory,and dossier requirements in IND application,greatly promoted the application quality of innovative biological products.However,compared to the Food and Drug Administration(FDA)and European Medicines Agency(EMA),our particular guidelines are insufficient,such as guideline on virus safety evaluation of biotechnological investigational medicinal products.This review investigated the questions raised by sponsors from 2018 to 2020,including the end of production cell(EOPC)and/or unprocessed bulk(UPB)testing and virus removal or inactivation validation.Meanwhile,sponsors submitted different dossiers due to differences in understanding of stage requirements of guidelines from domestic and abroad.Based on the guidelines of virus safety from NMPA,FDA,and EMA,and the technical considerations,this review puts forward personal suggestions on the adventitious agents testing and virus removal or inactivation validation in manufacturing process,aim to ensure virus safety of innovative monoclonal antibody products in clinical trials.

关 键 词：创新单抗药物 申报临床试验 病毒安全性 生产终末细胞和/或细胞收获液 病毒去除或灭活验证 技术考量 

分 类 号：R915[医药卫生—微生物与生化药学]