(507f) Implementation of Advanced Process Control System into Continuous Pharmaceutical Manufacturing Pilot-Plant

Advanced process control (APC) such as model predictive control (MPC) has several advantages in compare to conventional control algorithms [1-3]. Therefore, the pharmaceutical industries are moving toward continuous manufacturing (CM) integrated with advanced process control (APC) system. This modernized integrated system 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. Therefore, this is still an open area of research.

The different control strategies for 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 and pre compression forces, tablet weight and hardness. The different control architectures under three control algorithms (PID, MPC, hybrid MPC-PID) have been implemented and compared for control of CPP’s and CQA’s. 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 assurance of CQA’s have been achieved through two levels strategy. In first level, the CPP’s and CQA’s are controlled in real time using advanced process control system while in second level, the none-confirming products are diverted in real time in waste to assure the final CQA’s of qualified tablet lots. This two level strategy assures the maximum production efficiency while assuring the final product quality. The drug concentration of blend is controlled before its compaction using PAT and MPC. An efficient control strategy for powder level control in a chute placed in between blender and tablet press unit operation of continuous tablet manufacturing process has been developed, implemented and evaluated [1]. A novel noninvasive technique based on change in electric field concept has been used for real time monitoring of powder level in continuous manufacturing pilot-plant. The sensor has been integrated with a control panel (DeltaV (Emerson)) through relays and charms. The control panel then send the signal (4-20 mA) to control platform where the control strategy, a program to operate the sensor and a program to convert the sensor signal into powder level have been implemented. Subsequently, an advanced model predictive controller as well as PID controller for powder level have been implemented into our continuous pharmaceutical manufacturing pilot-plant facility. The performance of both control strategies have been practically evaluated for set point tracking and disturbance rejection. The APC has been used to control tablet press as well [2]. The pre and main compression forces have been controlled using a novel decoupled strategy so that the desired tablet weight and hardness can be achieved simultaneously. Similarly, the other CPP’s and CQA’s have been controlled. It has been observed that the MPC performs better than PID. A systematic methodology for material traceability has been also developed and coupled with integrated control system [3]. 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) and cloud system.

The objective of this presentation is to demonstrate the performance of integrated advanced process control (APC) system implemented into continuous pharmaceutical tablet manufacturing pilot-plant.

References
1. Singh, R. (2017). A novel continuous pharmaceutical manufacturing pilot-plant: Advanced model predictive control. Pharma, Issue 28, PP 58-62.
2. Bhaskar, A., Barros, F. N., Singh, R. (2017). Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process. International Journal of Pharmaceutics, 534 (1-2), 159-178.
3. Billups, M., Singh, R. (2018). Material Traceability in Continuous Pharmaceutical Tablet Manufacturing. Pharmaceutical Technology 42 (2), 32-35, 59.