‘Quality by Design’ approach for the analysis of impurities in pharmaceutical drug products and drug substances

The pharmaceutical industry is highly regulated by quality policies. The concept of risk management is strongly integrated into the quality assurance system to ensure pharmaceuticals' quality and patients' safety. In the context of quality control, the detection of impurities in raw materials and finished products is a major concern. It can be challenging for analytical scientists to meet specificity/selectivity and sensitivity requirements. Obviously, separation techniques are widely used for the detection of impurities but the method development required to achieve Analytical Target Profile (ATP) concerns is often challenging. Therefore, to ensure pragmatic and systematic methods development and simultaneously manage the risk associated with analytical methods, the principles of Quality by Design (QbD) should be applied. This paper provides an overview of QbD principles and statistical strategies (mainly DoE-DS approach) which can be applied to impurity detection methods, as well as a review of the literature where QbD has been applied to these types of analytical methods.