Quality (philosophy)

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Quality by Design

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Organic Process Research & Development

This review presents the Analytical Quality by Design (AQbD) concept, an extension of Quality by Design (QbD), which was introduced in 2004 by the U.S. Food and Drug Administration (FDA) and approved in 2005 by the International Conference on Harmonisation (ICH). AQbD is a systematic approach to method development, controlling all stages of the analytical procedure life cycle. It includes a definition of the analytical target profile (ATP), identification of critical method parameters or factors, and selection of critical method attributes (CMAs) or responses. Screening and response-surface experimental designs allow the recognition of significant factors and their optimization by statistical analysis. The factor–response relationship is described by a mathematical model, which is able to predict the optimal response. Multivariate combinations of factors fulfilling the CMA requirements are presented in the design space or method operable design region (MODR), where robust method performance is ensured. This review presents the theoretical background of AQbD for method development and its workflow through recently published cases in which the AQbD concept proved to be a reliable and effective approach. Analytical methods developed by using the AQbD approach are highly robust, are easily validated, have shorter run times, and are capable of determining a higher number of analytes in one run compared with the methods developed by the one-factor-at-a-time (OFAT) approach.

Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances