Model predictive control in pharmaceutical continuous manufacturing: A review from a user's perspective.

Pharmaceutical continuous manufacturing is considered as an emerging technology by the regulatory agencies, which have defined a framework guided by an effective quality risk management. With the understanding of process dynamics and the appropriate control strategy, pharmaceutical continuous manufacturing is able to tackle the Quality-by-Design paradigm that paves the way to the future smart manufacturing described by Quality-by-Control. The introduction of soft sensors seems to be a helpful tool to reach smart manufacturing. In fact, soft sensors have the ability to keep the quality attributes of the final drug product as close as possible to their references set by regulatory agencies and to mitigate the undesired events by potentially discard out of specification products. Within this review, challenges related to implementing these technologies are discussed. Then, automation control strategies for pharmaceutical continuous manufacturing are presented and discussed: current control tools such as the proportional integral derivative controllers are compared to advanced control techniques like model predictive control, which holds promise to be an advanced automation concept for pharmaceutical continuous manufacturing. Finally, industrial applications of model predictive control in pharmaceutical continuous manufacturing are outlined. Simulations studies as well as real implementation on pharmaceutical plant are gathered from the control of one single operation unit such as the tablet press to the control of a full direct compaction line. Model predictive control is a key to enable the industrial revolution or Industry 4.0.