Use of PAT for Active Pharmaceutical Ingredient Crystallization Process Control

Authors:	Wu Huiquan, FDA/CDER, United States Hussain Ajaz S., FDA/CDER, United States
Topic:	8.4 Control of Biotechnological Processes
Session:	From Drug Design to Production: Control Issues
Keywords:	process control, process models, product quality, knowledge-based control, systems concepts, on-line control.

Abstract

Crystallization of active pharmaceutical ingredient (API) or pharmaceutical drug substances is a crucial unit operation. In this paper challenges and scientific progress over the last two decades in the areas of pharmaceutical crystallization thermodynamics, kinetics, polymorphism, process modeling, and process control were discussed. Effective utilization of such scientific knowledge for optimized control of API crystallization process was discussed. A conceptual PAT framework for API crystallization process control was proposed. Three case studies from the literatures were discussed as hypothetical examples to illustrate the application of PAT framework to pharmaceutical crystallization process.