Control Strategy Development for QbD Submission

The process control strategy for Lilly compound Edivoxetene^.HCl was developed and refined by unit operation characterization / process parameterization, and reaction kinetic modeling to understand the rates of impurity formation.  Thermodynamic impurity rejection efficiencies were established based on development of ternary phase diagrams and determination of eutectic compositions for the crystallization process along with spiking studies.  The specifications for starting material and intermediate were set based on our understanding of the fate of impurities.  Furthermore, a systematic approach to criticality assessment was adopted to determine the overall design space of the manufacturing process, which contained all critical process parameters.  This presentation provides an example of how QbD was used to establishing the control strategy for drug substance manufacturing process.