摘要
近年来,新兴的医疗药物产品细胞和基因治疗(cellular and gene therapy,CGT)产品相关科学理论、技术手段、临床医疗实践发展蓬勃。由于CGT产品本身的特殊性、生产制造上的独特性和复杂性,以及生产技术的不断革新和优化,CGT产品在生产制造上的成功变更往往是CGT产品在临床和上市商业化成功的重要保障。生产制造中的变更是产品生产中的关键环节,能否可行、适时实施、被合理适度监管,正在成为目前CGT产品公司和监管部门关注的重点。为促进我国CGT产品的研发和上市商业化产业与国际接轨,增强和巩固该产业在全球的竞争优势,本研究基于美国食品药品管理局(FDA)2023年7月最新出台的“人体CGT产品的生产变更和可比性”指南,结合国际上对生物医药产品生产变更的监管政策,在梳理当前CGT产品发展现状、阐述CGT产品特征的基础上,探讨CGT产品在临床试验期间和上市后进行生产制造的变更,以及对生产变更进行可比性研究的实施策略和符合监管要求的实施方案,并指出FDA指南的独特之处:①该指南专门针对CGT产品的生产变更和可比性研究;②考虑到CGT产品性质的特殊性、结构的复杂性、生产工艺的新颖性以及分析方法的多样性,该指南提出了全面且详细的建议和要求;③该指南是少有的既能针对上市产品、又能针对临床产品的生产变更和可比性研究的指南;④该指南追求生产变更管理细致化、建议和要求规范化。该指南不仅对CGT产品研发者和生产企业具有指导作用,而且对监管部门也有积极的借鉴意义。
In recent years,the emerging field of cellular and gene therapy(CGT)products has seen significant growth in scientific theory,technical advancements,and clinical medical practice.Due to the unique nature of CGT products,uniqueness and complexity in manufacturing processes,and ongoing technological innovations and optimizations,successful changes in product research and manufacturing have become a crucial factor for the clinical and commercial success of CGT products.Changes in product research and manufacturing are pivotal in the drug production,and whether the changes are feasible,timely implemented,and subject to reasonable oversight is now a focus for CGT companies and regulatory authorities.To align China′s CGT product development and commercialization with international standards and strengthen the industry′s global competitiveness,this study is based on the latest guidance“Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products”issued by the U.S.FDA in July 2023.It also considers international regulatory policies regarding changes in the production of biopharmaceutical products.Building on an overview of the current state of CGT products development and the characteristics of CGT products,this study explores changes in production and manufacturing during clinical trials and post-market phases,and also discusses strategies for implementing comparability studies of production changes and the implementation plan that meets regulatory requirements.The unique aspects of the FDA guidance are highlighted:①This guidance is specifically aimed at manufacturing changes and comparability studies of CGT products;②This guidance puts forward comprehensive and detailed suggestions and requirements taking into account the particularity,the complexity of the production structure,the novelty of the production process,and the diversity of analytical methods of CGT products;③This guidance is rare in that it addresses both commercial and clinical products′manufacturing changes and com
作者
杜新
DU Xin(Shenzhen Evergreen Therapeutics,INC,Guangdong Shenzhen 518038,China)
出处
《中国医药导刊》
2023年第9期873-880,共8页
Chinese Journal of Medicinal Guide
关键词
CGT产品
生产变更
变更管理
可比性研究
监管指南解读
CGT products
Manufacturing changes
Change management
Comparability studies
Interpretation of regulatory guidance
