基于QbD理念的单克隆抗体生物类似药研发缺陷管理策略研究

Defect Management Strategies in the Research and Development of Monoclonal Antibody Biosimilars Based on QbD Concept

目的为生物类似药的早期研发管理提供参考。方法在阿达木单克隆抗体生物类似药研发、申报实践基础上,结合相关法规、指导原则的要求及审评案例,以药事监管的视角分析单克隆抗体生物类似药研发过程中存在的药学研究缺陷。基于质量源于设计(QbD)理念,从产品质量属性研究全面性、工艺过程控制科学性、外源因子安全性评估充分性、稳定性研究完整性、研究数据规范性五方面提出对应的缺陷管理策略。结果与结论研究缺陷主要表现在药物质量属性研究不全面、工艺过程控制不科学、外源因子安全性评估不充分、稳定性研究不完整、研究数据不规范等方面。在充分研究产品质量属性的前提下,通过产品设计-工艺控制-质量实现实施缺陷管理,提高生物类似药的研发效率及产品研发和申报质量。

Objective To provide a reference for the early research and development(R&D)management of biosimilars.Methods Based on the R&D and application practice of Adalimumab monoclonal antibody biosimilars,combined with relevant regulations,guiding principles,and evaluation cases,the pharmaceutical research deficiencies in the R&D process of monoclonal antibody biosimilars were analyzed from the perspective of pharmaceutical supervision.Based on the concept of Quality by Design(QbD),corresponding defect management strategies were proposed for the comprehensiveness of product quality attribute research,scientificity of process control,adequacy of safety assessment of exogenous factors,completeness of stability research,and standardization of research data.Results and Conclusion The research deficiencies mainly manifest in five aspects:incomplete research on drug quality attributes,unscientific process control,insufficient safety assessment of exogenous factors,incomplete stability research,and non-GXP compliant research data.On the premise of fully studying the product quality attributes,defect management is implemented through product design-process control-quality implementation to improve the R&D efficiency of biosimilars,and the quality of product research and application.