Advanced process automation of a pharmaceutical continuous wet granulation line: Perspectives on the application of a model predictive control from solid feeders to dryer

Abstract

Pharmaceutical continuous manufacturing provides the appropriate tools (e.g. the understanding of process dynamics and appropriate and adaptable control strategy) in order to deal with Quality-by-Design expectations and even to the future smart manufacturing described by Quality-by-Control. Those tools form part of the given framework of the regulatory agencies led by an effective quality risk management. Soft sensors and control algorithms such as model predictive control are stepping stones for more agile processes and increased robustness by keeping the quality attributes of the final drug product in their acceptable ranges and by mitigating undesired events. The implementation of a model predictive control (MPC) system on a pharmaceutical continuous manufacturing plant for the wet granulation process is described. The control objectives and strategy are presented as well as the selected variables, the process dynamics identification, the MPC performance and its specific tuning where a commercial software has been used, setting the framework of this study. MPCs have been applied successfully on two pharmaceutical drug products (Diclofenac and Paracetamol): an accurate control of the API content and of the LOD was achieved in order to produce a constant quality of tablets on both drug products. In addition, some of the process parameters have been identified as mandatory to be step tested for each change of drug product, leading to a simplified MPC implementation.