(301e) Implementation of Model-Based Control Strategies in Manufacturing of Drug Substance and Drug Product

During the last years the shift from batch to continuous manufacturing was accompanied by extensive research in development and testing of advanced control concepts based on in-line process data and process models. A maturity level of these methods is now reached to enable transfer to industrial pharmaceutical processes. Still the majority of commercial manufacturing lines remain at an automation level, at which end product testing, parametric control or process execution within strictly defined spaces are applied to maintain product quality and a state of control. Emphasis is now required, especially for new drug products, to make use of the aforementioned alternative approaches.

This talk will give a step-wise overview of the development and implementation of model-based strategies for process automation. It will include the PAT concept, the control strategy, process model development and controller synthesis. Examples will be shown for different manufacturing processes. Process automation for start-up, steady state operation and exceptional events handling will be discussed for an API synthesis and a solid dosage production process. In the first one, mesalazine is continuously synthesized in flow via nitration, separation, substitution and hydrogenation. In the second one, tablets are produced via pelletization of hot melt extruded strands. The talk will outline opportunities and challenges of the model-based automation approach.