Abstract

The need for consistency in analytical method development reinforces the dependence of pharmaceutical product development and manufacturing on robust analytical data. The Analytical Quality by Design (AQbD), akin to the product Quality by Design (QbD) endows a high degree of confidence to the method quality developed. AQbD involves the definition of the analytical target profile as starting point, followed by the identification of critical method variables and critical analytical attributes, supported on risk assessment and design of experiment tools for the establishment of a method operable design region and control strategy of the method. This systematic approach moves away from reactive troubleshooting to proactive failure reduction. The objective of this review is to highlight the elements of the AQbD framework and provide an overview of their implementation status in various analytical methods used in the pharmaceutical field. These methodologies include but are not limited to, high-performance liquid chromatography, UV-Vis spectrophotometry, capillary electrophoresis, supercritical fluid chromatography, and high-performance thin-layer chromatography. Finally, a critical appraisal is provided to highlight how regulators have encouraged AQbD principles application to boost the prevention of method failures and a better understanding of the method operable design region (MODR) and control strategy, ultimately resulting in cost-effectiveness and regulatory flexibility.

摘要

分析方法开发一致性的需求强化了药品开发和制造对可靠分析数据的依赖。分析质量源于设计 (AQbD) 类似于产品质量源于设计 (QbD)，赋予所开发的方法质量高度信心。AQbD 涉及以分析目标概况的定义为起点，然后识别关键方法变量和关键分析属性，以风险评估和实验工具设计为支持，以建立方法可操作的设计区域和方法的控制策略。这种系统化方法从被动式故障排除转向主动式故障减少。本次审查的目的是强调 AQbD 框架的要素，并概述其在制药领域使用的各种分析方法中的实施状况。这些方法包括但不限于高效液相色谱法、紫外-可见分光光度法、毛细管电泳、超临界流体色谱法和高效薄层色谱法。最后，提供了批判性评估，以强调监管机构如何鼓励应用 AQbD 原则来促进方法失败的预防，并更好地理解方法可操作设计区域 (MODR) 和控制策略，最终实现成本效益和监管灵活性。