分析方法是生物制品质量控制的基础,准确可靠的分析方法能够提升标准制定的科学性.生物制品分析方法具有变异大的特点,更加凸显了对分析方法质量控制的要求.分析方法质量源于设计(analytical quality by design,AQbD)为质量源于设计(quality by design,QbD)在分析方法生命周期管理中的应用.近年随着分析方法开发的相关法规文件不断推出,AQbD已用在药品包括疫苗的分析方法中,主要通过分析目标概要(analytical target profile,ATP)设定、风险分析、实验设计(design of experiment,DOE)和方法验证来获得符合ATP要求的准确度、精密度和专属性等指标,并明确容忍区间、预测区间、方法总变异、方法能力指数和方法误判率等能力指标,为疫苗分析方法的开发和评价提供支持.本文介绍AQbD国内外相关法规文件及其在疫苗中的应用进展,推动AQbD用于我国疫苗质控和评价.
Abstract
Analytical methods are the basis of quality control for biopharmaceuticals.Accurate and reliable analytical methods can improve the scientific rigor of standard setting.Biopharmaceutical analytical methods are often characterized by large variations,which further highlights the requirements for quality control of analytical methods.Analytical quality by design(AQbD)is the application of quality by design(QbD)principles in the lifecycle management of analytical methods.In recent years,with the continuous release of relevant regulatory documents for analytical method development,AQbD has been used in analytical methods of drugs,including vaccines.The key steps of AQbD include setting the analytical target profile(ATP),risk analysis,design of experiments(DoE),and method validation to obtain accuracy,precision,and specificity that meet the ATP requirements.Tolerance intervals,prediction intervals,total variation of the method,method capability index,and method misjudgment rate,and other ability indicators are also defined as capability metrics to support the development and evaluation of vaccine analytical methods.This article introduces the relevant regulatory documents of AQbD at home and abroad and the progress of its application in vaccines,promoting the use of AQbD for vaccine quality control and evaluation in China.
关键词
分析方法质量源于设计(AQbD)/质量源于设计(QbD)/疫苗/实验设计(DOE)
Key words
Analytical quality by design/Quality by design/Vaccine/Design of experiments
维普
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