Development of a Control Strategy for a Defluorinated Analogue in the Manufacturing Process of Casopitant Mesylate

Casopitant mesylate was identified as part of the search for drugs with activity on the Central Nervous System (CNS) by GlaxoSmithKline. During late-phase development studies to develop the manufacturing process, a new impurity was found. This synthetic impurity, a defluorinated analogue of the drug substance, is discussed in detail to show the process development studies carried out to ensure quality control for the final drug substance following the principles of quality by design. The process understanding gained, in combination with risk analysis, allowed the development of a control strategy for enhanced level of quality assurance. This Control Strategy allows moving the control of this impurity to the point of origin instead of testing in the drug substance.