Product Development and Supply, Medicines Research Centre , GSK , Gunnels Wood Road , Stevenage SG1 2NY , U.K.
Technical Research and Development , GSK Vaccines , via Fiorentina 1 , 53100 Siena , Italy.
Anal Chem. 2019 Feb 19;91(4):2577-2585. doi: 10.1021/acs.analchem.8b04596. Epub 2019 Feb 8.
Quality by design (ICH-Topic Q8) requires a prospective summary of the desired quality characteristics of a drug product. This is known as the Quality Target Product Profile (QTPP), which forms the basis for the design and development of the product. An analogous term has been established for analytical procedures called the Analytical Target Profile (ATP). The ATP, in a similar fashion to the QTPP, prospectively summarizes the requirements associated with a measurement on a quality attribute which needs to be met by an analytical procedure. Criteria defined in the ATP relate to the maximum uncertainty associated with the reportable result that is required to maintain acceptable confidence in the quality decision made from the result. The ATP is used to define and assess the fitness of an analytical procedure in the development phase and during all changes across the analytical lifecycle. One or more analytical procedures can meet the requirements of an ATP. The ATP can be applied to any quality attribute across any pharmaceutical modality where an analytical procedure is used to generate a reportable result, and this paper provides examples from three of these modalities: small molecules, oligonucleotides, and vaccines. Some key performance characteristics will be discussed for each ATP, namely specificity, accuracy, and precision, taking into account the expected range of the analyte. The combination of accuracy and precision into a combined uncertainty characteristic is also discussed as a more holistic approach. The use of the ATP concept will help focus attention on the properties of a method which impact quality decisions rather than method descriptions and may enable greater regulatory flexibility across the lifecycle using established conditions based on method performance criteria as proposed in the Step 2 version of ICHQ12. The revision of ICHQ2(R1) and development of the new ICHQ14 guideline (Analytical Procedure Development) will provide a golden opportunity to harmonize the definition of new QbD concepts such as the ATP.
质量源于设计（ICH 主题 Q8）要求对药物产品的预期质量特性进行总结。这被称为质量目标产品概况（QTPP），它是产品设计和开发的基础。类似的术语也已为分析程序建立，称为分析目标概况（ATP）。与 QTPP 类似，ATP 前瞻性地总结了与需要通过分析程序满足的质量属性测量相关的要求。ATP 中定义的标准与报告结果所需的最大不确定性有关，该不确定性需要对从结果做出的质量决策保持可接受的信心。ATP 用于在开发阶段以及整个分析生命周期中的所有变更期间定义和评估分析程序的适用性。一个或多个分析程序可以满足 ATP 的要求。ATP 可应用于任何使用分析程序生成可报告结果的药物模式的任何质量属性，本文提供了来自这三种模式的示例：小分子、寡核苷酸和疫苗。将讨论每个 ATP 的一些关键性能特征，即专属性、准确性和精密度，并考虑到分析物的预期范围。还将讨论将准确性和精密度组合为综合不确定度特征的方法，这是一种更全面的方法。使用 ATP 概念将有助于关注影响质量决策的方法特性，而不是方法描述，并且可能会在整个生命周期中使用基于方法性能标准的既定条件，从而根据 ICHQ12 的 Step 2 版本实现更大的监管灵活性。ICHQ2(R1)的修订和新 ICHQ14 指南（分析程序开发）的制定将为协调新 QbD 概念（如 ATP）的定义提供绝佳机会。
