Modeling-Based Approach Towards Quality by Design for the Ibipinabant API Step

Abstract

This work presents a process modeling-based methodology towards quality by design that was applied throughout the development lifecycle of the ibipinabant API step. By combining mechanistic kinetic modeling with fundamental thermodynamics, the degradation of the API enantiomeric purity was described across a large multivariate process knowledge space. This knowledge space was then narrowed down to the process design space through risk assessment, target quality specifications, practical operating conditions for scale-up, and plant control capabilities. Subsequent analysis of process throughput and yield defined the target operating conditions and normal operating ranges for a specific pilot-plant implementation. Model predictions were verified via results obtained in the laboratory and at pilot-plant scale. Future efforts were focused on increasing fundamental process knowledge, improving model confidence, and using a risk-based approach to reevaluate the design space and selected operating conditions for the next scale-up campaign.