Quality by Design approach: why to use it?

Recent regulatory documents in the pharmaceutical field strongly recommend the implementation of Quality by Design (QbD) approach in pharmaceutical product development. QbD strategy has been gaining increased interest in drug analysis, as it can be effectively applied to the development of analytical methods, leading to enhanced knowledge, better analytical performances and higher flexibility from the regulatory point of view. QbD framework for the development of analytical separation methods has been recently presented and is mainly based on risk assessment and multivariate tools. It begins with the definition of the goal of the method, systematic scouting of alternative methods, assessment of the method for risks using structured tools, evaluation of the effects of critical process parameters on critical quality attributes by applying experimental design, identification of the design space and finally development of a control strategy to ensure method performances. The design space represents the core of QbD approach and is defined as the multidimensional region where the analytical method provides quality outputs with selected probability. DS concept marks the difference with the classical analytical method development, where the target of the optimization process was only the definition of a single optimum point. Experimental design strongly underpins QbD approach, providing a greater opportunity to find optimum conditions from a limited number of experiments, allowing significant interactions between variables to be found and predictive maps of the considered responses to be obtained. Thus, QbD includes all aspects and advantages of multivariate techniques, but it also adds a concept of probability which allows the achievement of analytical assurance of quality. Examples illustrating the usefulness of QbD approach in the optimization of capillary electrophoresis methods for drug analysis will be presented.