Recent applications of analytical quality-by-design methodology for chromatographic analysis: A review

Abstract

Analytical Quality-by-Design (AQbD) represents a systematic methodology for method development. The pharmaceutical and biopharmaceutical industries have increasingly recognized and applied AQbD concepts, guided by the overall framework provided by ICH. AQbD is established to ensure that an analytical procedure is fit for its intended purpose throughout its entire lifecycle, leading to a well-understood and purpose-driven method. It guides each stage of the analytical process lifecycle by establishing the Analytical Target Profile (ATP), identifying critical method parameters (CMPs), and selecting critical method attributes (CMAs). By employing screening and response-surface experimental designs, significant factors are pinpointed and optimized through statistical analysis. This methodology aids in defining the design space or Method Operable Design Region (MODR) to ensure consistent method performance. This review delves into the foundational principles of AQbD for method development and presents its latest applications in the period 2019–2024 with reference to chromatographic analysis of both non-synthetic and synthetic compounds in different sample matrices. The implementation of AQbD proved to generate more robust chromatographic methods, enhancing their efficiency in the process. Nevertheless, its adoption can be hindered owing to the necessity for a comprehensive grasp of statistical analysis and experimental design, coupled with the absence of standardized directives or regulatory prerequisites.