Quality-by-design (QbD) approach for HPLC analytical method development: principles, methodology, regulatory perspectives, and future directions

Mohd Aman Ansari*, Harshit Gautam

University institute of Pharmaceutical Education & research, University Kota, Kota, Rajasthan, India

Refer this article

Mohd Aman Ansari, Harshit Gautam, 2026. Quality-by-design (QbD) approach for HPLC analytical method development: principles, methodology, regulatory perspectives, and future directions. Journal of medical pharmaceutical and allied sciences, V 15, I 4, Pages 01 – 10. Doi: https://doi.org/10.55522/jmpas.V15I4.7102.

ABSTRACT

Quality-by-Design (QbD) has transformed pharmaceutical analytical development by moving from empirical, trial-and-error approaches to systematic, science-based frameworks. This review presents a comprehensive review on the application of QbD principles, also known as Analytical Quality by Design (AQbD), to the development of high-performance liquid chromatography (HPLC) methods. This article is about the basic concepts of AQbD, such as Analytical Target Profile (ATP), Critical Method Attributes (CMAs), Critical Method Parameters (CMPs) and importance of risk assessment and Design of Experiments (DoE) in the development of robust methods. The methodological workflow is described from initial scoping through to the establishment of the Method Operable Design Region (MODR) and the implementation of lifecycle control strategies. Detailed coverage of regulatory views such as the enhanced approach in ICH Q14 and the USP Chapter <1220> lifecycle framework. Recent applications in pharmaceutical dosage forms, bioanalytical and stability indicating methods are reviewed to show the versatility and effectiveness of AQbD. The combination of AQbD and Green Analytical Chemistry (GAC) principles as a new paradigm for sustainable method development is discussed. Emerging trends like integration of artificial intelligence, green analytical chemistry principles and continuous manufacturing paradigms are explored as future directions. AQbD is an indispensable paradigm for modern HPLC method development, providing improved robustness, regulatory flexibility, and analytical efficiency, while guaranteeing consistent product quality and patient safety, the review concludes.

Keywords:

Analytical quality by design, Design of experiments, Method operable design region, ICH Q14.

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