摘要
多糖结合疫苗质量高度依赖于早期科学设计与全生命周期控制。本文基于质量源于设计(Quality by Design,QbD)理念,从菌种驱动的上下游工艺开发、多糖结构导向的结合工艺设计、载体蛋白适配性优化及临床需求驱动的工艺迭代策略等维度构建系统开发框架。通过关键质量属性(critical quality attributes,CQAs)与关键工艺参数(critical process parameters,CPPs)的动态匹配实现工艺稳健性。针对多糖结合疫苗的分子异质性、多价次迭加及批间差异等复杂挑战,提出基于产品特性的质控策略,涵盖特异性官能团质控、多糖完整性确认、载体蛋白纯度控制、多价疫苗交叉干扰规避以及检测方法选择和交叉验证等核心问题,并整合过程分析技术(process analytical technology,PAT)与持续工艺验证(continuous process verification,CPV)构建全过程及从早期开发到商业化的全生命周期控制网络,推动多糖结合疫苗的国际标准接轨。本文从监管科学视角出发,系统阐述QbD理念在保障疫苗质量与临床有效性中的核心价值,为多糖结合疫苗的理性开发、质量提升及全生命周期管理提供科学指导。
The quality of polysaccharide conjugate vaccines is critically dependent on scientific design during early development and lifecycle control.Guided by the Quality by Design(QbD)framework,a systematic development strategy was established,encompassing strain-driven upstream/downstream process development,polysaccharide structure-oriented conjugation process design,carrier protein compatibility optimization,and clinical demand-driven iterative process refinement.By dynamically aligning critical quality attributes(CQAs)with critical process parameters(CPPs),process robustness was ensured.To address complex challenges such as molecular heterogeneity,multi-valent formulation,and batch variability.tailored quality control strategies were proposed based on product characteristics.These encompassed core issues such as functional group-specific control,polysaccharide integrity verification,carrier protein purity assurance,mitigation of crossinterference in multi-valent vaccines,and method selection and cross-validation.Furthermore,the process analytical technology(PAT)and continuous process verification(CPV)were integrated to construct a lifecycle control network spanning early development to commercialization,thereby advancing the alignment of polysaccharide conjugate vaccines with international standards.From a regulatory science perspective,this article systematically elucidates the pivotal role of QbD in safeguarding vaccine quality and clinical efficacy,providing scientific guidance for the rational development,quality enhancement,and lifecycle management of polysaccharide conjugate vaccines.
作者
杨丹
胡琳
李茂光
张影
李小静
叶强
李敏
YANG Dan;HU Lin;LI Maoguang;ZHANG Ying;LI Xiaojing;YE Qiang;LI Min(Center for Drug Evaluation,National Medical Products Administration,Beijing 100076,China;不详)
出处
《中国生物制品学杂志》
2025年第8期1012-1018,1024,共8页
Chinese Journal of Biologicals
基金
药品监管科学全国重点实验室第一批课题(2023SKLDRS0137)。
关键词
多糖结合疫苗
质量源于设计
工艺开发
质控策略
监管科学
Polysaccharide conjugate vaccines
Quality by Design(QbD)
Process development
Quality control strategy Regulatory science
