Abstract

STRATEGIC IMPLEMENTATION OF ANALYTICAL QUALITY BY DESIGN (AQbD) IN HPLC METHOD DEVELOPMENT FOR PHARMACEUTICAL QUALITY ASSURANCE: A COMPREHENSIVE REVIEW

Lalit Kumar*, Hitesh Kothari, Anju Goyal

ABSTRACT

The pharmaceutical sector is witnessing a fundamental transition from empirical "One- Factor-At-A-Time" (OFAT) methodologies toward the highly structured "Analytical Quality by Design" (AQbD) paradigm. This review aims to critically evaluate how AQbD enhances the robustness and reliability of High-Performance Liquid Chromatography (HPLC) methods throughout their operational lifecycle. A systematic synthesis of literature was conducted using Scopus, Web of Science, and PubMed, targeting developments between 2016 and 2025. The study investigates the synergy between quality risk management (ICH Q9) and statistical optimization (DoE). Analysis reveals that traditional methods often suffer from "robustness gaps," leading to frequent Out-of-Specification (OOS) results during laboratory transfers. Conversely, AQbD utilizes a predefined Analytical Target Profile (ATP) and a Method Operable Design Region (MODR) to ensure that analytical quality is a built-in feature rather than an afterthought. The integration of the new ICH Q14 guidelines provides a modernized regulatory pathway for this approach. Implementing AQbD is no longer a luxury but a necessity for ensuring "Right-First-Time" analytical results. The review identifies the convergence of AQbD with Green Analytical Chemistry as the next critical step for sustainable pharmaceutical quality assurance.

Keywords: Analytical Quality by Design (AQbD), Design of Experiments (DoE), HPLC, Method Operable Design Region (MODR), ICH Q14, Robustness.