Drilling into “Quality by Design” Approach for Analytical Methods

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.

Keywords:

• Analytical methods
• analytical quality by design (AQbD)
• analytical methodologies
• risk assessment

Acknowledgments

We acknowledge the Coimbra Chemistry Centre, supported by FCT, through the Project UID/QUI/00313/2020. The views expressed in this publication do not reflect the official views of Laboratórios Basi.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

Lucas Chiarentin acknowledgments the PhD grant [PD/BDE/150717/2020] assigned by Fundação para a Ciência e a Tecnologia (FCT), Portugal and Laboratórios Basi Indústria Farmacêutica S.A. from Drugs R&D Doctoral Program.