(438f) Integrated Control and Data Management System for Continuous Pharmaceutical Manufacturing Process

Continuous manufacturing (CM) is evolving as a preferred platform for pharmaceutical products involving solid dosages forms. One advantages of CM among others is that the product quality can be controlled in real time and thereby its open the possibilities of achieving Quality by Control (QbC) and real time release (RTR) paradigm. However, there are different levels of challenges associated with design and implementation of an efficient control system into pharmaceutical manufacturing plant. Identification of right control strategies such as feedforward (FF), feedback (FB), or combined FF/FB¹ as well as right control algorithms such as PID, MPC, or hybrid MPC-PID is often a tough decision that need to be made prior to implementation of integrated control system into the manufacturing plant². Selection of a right control strategy and algorithm is mandatory task both for efficient manufacturing as well as regulatory point of view. Therefore, the different control options need to be evaluated and the best integrated control system needs to be implemented into the pilot-plant. The integrated control system is then need to be coupled with material traceability framework for real time identification of batches so that the product can be recall in case if needed. The continuous manufacturing is a data rich process and therefore a systematic data management framework is also desired to be implemented to collect, store and manage all the relevant data in real time.

In this work, different control strategies for direct compaction continuous tablet manufacturing process has been developed and implemented into our pilot-plant facility using industry standard control platform. The critical control variables are drug concertation, powder level, main compression force, tablet weight and hardness. Both, feedback (FB) as well as feedforward (FF) control strategies have been implemented into the pilot-plant. Feedback (FB) control strategy has been compared with a combined feedforward/feedback (FF/FB) control strategy. A novel method for real time monitoring of powder density has been developed and integrated with feedforward control loop. The feedforward control loop takes the powder bulk density signal as an input and mitigate the effect of variations in powder bulk density on CQA’s proactively and thereby reduces the rejections significantly in compare to only feedback control strategy. Three control algorithms (PID, MPC, hybrid MPC-PID) have been also implemented and compared for feedback loops. The flexible control system is designed in such a way that any control scheme can be easily selected. The control system is also modular in nature that can be easily transferred to any other control platform and manufacturing plant. The continuous tablet manufacturing pilot-plant runs under each control scheme and their performance are evaluated and thereby a best control system has been identified. A systematic methodology for material traceability has been also developed and coupled with integrated control system. The methodology starts with material and process specifications followed by scanning the powder drums and transmitting the material and time information to the control platform. The control platform then utilizes the information stored in the database, generated through residence time distribution model and information collected through real time monitoring to track the material during continuous manufacturing. All the relevant data generated during continuous manufacturing has been systematically collected, stored and organized in a data hub (OSI PI). The PAT data has been collected through PAT data management tool (synTQ) and then transferred to the PI system while the other operational data has been collected in control platform (DeltaV) and send to PI system via OPC communication. Finally, the data has been transferred to the cloud system for enterprise wise efficient sharing and applications.

The objective of this presentation is two-fold: first to evaluate the performance of integrated control system of continuous pharmaceutical tablet manufacturing process and then to highlight the material traceability and data management framework.

References

1. Singh, R., Muzzio, F., Ierapetritou, M., Ramachandran, R. (2015). A combined feed-forward/feed-back control system for a QbD based continuous tablet manufacturing process. PROCESSES Journal, 3, 339-356.
2. Haas, N. T., Ierapetritou, M., Singh, R. (2017). Advanced model predictive feedforward/feedback control of a tablet press. Journal of Pharmaceutical Innovation, 1-14, DOI 10.1007/s12247-017-9276-y.