Implementing Quality by Design (QbD) in Chromatography

Abstract

Analytical methods are required to be developed at different stages of the pharmaceutical product life cycle. These activities if properly not streamlined based on the knowledge of science and process understanding may lead to a very costly and time consuming procedure. Pharmaceutical industries are striving for new policy and/or new element which can be added/replaced the existing elements of quality and risk management system. Quality by design (QbD) approach is one of the alternatives where systematic implementation of Quality Management programme can be established by better knowledge of the method parameters. Recently the concept has been also appreciated by different regulatory, especially by EMA (Europe Medicines Agency) and other ICH countries authorities over the globe. When using QbD concept for development of analytical method, analytical chemist in factstudy the additive and interactive effects of all method parameters on its continual performance. Further by using statistical mockups method operable design region (MODR) is determined. Changes within MODR are not significant and revalidation of the method is not required. Current article reviews how QbD approach can be more expressively used for chromatographic analytical method development for pharmaceuticals. OFAT) development has high risk in method failure and always requires revalidation protocol after method transfer or during alternative method development; thereby it has been increasing the cost of the method. The later approach is Analytical Quality by Design (AQbD) which explores scientific understanding in method implementation sequences and starts with product quality that relates the risk assessment in method choice and then between method parameter and expected method results and finally a region for high robust and cost effective approach. Design of Experiment (DoE) is a part of AQbD, and it represents the interaction among the input variables that ultimately affect the method response and results. AQbD paradigm is a preferred and recommended strategy to be followed in analytical method development so as to attain regulatory flexibility and reduce Out of specification (OOS), Out of term (OOT) and Out of control (OOC) results and when this approach is used to study any chromatographic method, the methods explores more knowledge of the parameters that has to be controlled and monitored during the life cycle of the method. The scope of AQbD approach is briefly represented in Figure 1. AQbD and Chromatography There a very less or no detailed literature published on how to implement AQbD approach in method life cycle. Nevertheless this approach is very widely known in development/optimization of pharmaceutical formulation or processes. Whenever an analyst thinks to apply DOE, he may have a misperception that the model uses more trials or practically it is difficult to select a design or interpret data