质量源于设计(QbD)在药物分析方法开发中的应用研究进展

质量源于设计(quality by design,QbD)是一种始于预先定义的目标,采用科学和风险管理的方法来增加对产品和过程的理解并用于过程质量控制的系统方法。QbD 主要用于制药工艺开发过程,但其核心思想与分析方法开发过程具有相通之处,因而分析方法质量源于设计(analytical quality by design,AQbD)应运而生。应用AQbD 时,需首先定义分析方法目标(analytical target profile,ATP),并根据目标对关键方法属性(critical method attributes,CMAs)和关键方法参数(critical method parameters,CMPs)进行全面评估,结合实验设计(design of experiment,DOE)和统计分析建立分析方法设计空间(design space,DS),并基于设计空间制定方法控制策略(control strategy),通过系统化、结构化、层层递进的方式建立分析方法,以提高分析结果的准确性和可靠性。目前,AQbD 已应用于HPLC、UPLC、CE、ELISA、UPLC-MS、LC-MS/MS 和GC-MS/MS 等分析方法的开发过程。本文综述了AQbD 基本组成部分、实施路径、在分析方法开发中的应用和未来发展趋势,以期对药物分析和药品质量控制工作提供借鉴。

Quality by design(QbD)is a new and systematic approach for the development of drugs. This approach begins with predefined objectives,and uses science-based risk management to gain the understanding of product and process. Although the QbD concept has been applied to the field of manufacturing process originally,the main idea is similar to the development of analytical methods. So the analytical quality by design(AQbD)came into being. When use the AQbD,the first step is to define the analytical target,followed by whole assessment about the critical method parameters aiming at the analytical target. The design of experiment and statistical analysis was combined to build a robustness design space for the analytical method. Finally,the control strategy for the analytical method was set up based on the design space. The analytical method was established by means of structured,systematic and progressive layers,which were beneficial to improve the accuracy and reliability of method. Currently,the AQbD principle has been used in the analytical method development of HPLC,UPLC,CE, ELISA,UPLC-MS,LC-MS/MS and GC-MS/MS,et al. This paper summary of the basic parts,implementation approach,application in the method development and future development,which offered a may provide a reference for the drug analysis and drug quality management.