(372h) FDA Considerations on Soft Sensor Development and Implementation for Crystallinity Monitoring and Control Strategy in Pharmaceutical Manufacturing

Crystallinity and morphology change are prevalent considerations in pharmaceutical manufacturing which may significantly impact drug manufacturability, drug quality, and patient safety. Among those analytical technologies that have been used, X-Ray Powder Diffraction (XRPD) has been the most utilized analytical technology for polymorphism characterization and analysis during pharmaceutical development and drug substance/drug product release for approved NDAs and ANDAs. In the past ten years, there have been significant advances in physical sensors, state-of-the-art analytical and material characterization techniques, and advanced data analytics and modeling tools. Those technology advances can accelerate drug development program, mitigate risk associated with product and manufacturing process, establish predictive process control scheme, and enable robust and consistent manufacturing process when integrated into manufacturing process design. In the past two decades, soft sensors or virtual sensors have become increasingly important when measurements of different characteristics and process dynamics can be combined. In process industry, soft sensors have been widely deployed for process fault detection and diagnosis, non-linear process control, and quality control, etc.

This presentation will discuss our recent progress on soft sensor research for crystallinity monitoring and control in high-risk drug product manufacturing where unit operations are prone to crystallinity or polymorphism change. Various modeling strategies have been employed to explore their utilities in regulatory science and practice domain. In addition, our current thinking on certain technical and regulatory considerations on this evolving area to facilitate implementation of advanced manufacturing in pharmaceutical area will be discussed.