Implementation of Advanced Hybrid MPC-PID Control System Into a Continuous Pharmaceutical Tablet Manufacturing Pilot-Plant

There is a need in pharmaceutical industry for the introduction of innovative manufacturing strategies based on continuous processing that is integrated with online monitoring tools , coupled with advanced control systems. This will enable the transition towards a desirable Quality by Design (QbD) , rather than Quality by Testing (QbT) , based manufacturing of the next generation of pharmaceutical products. This is translated to reduced time , and resources for product development while satisfying the strict regulatory expectations , flexible market demands , operational complexities and economic limitations. Model predictive control (MPC) has proven to be an effective control strategy over the last twenty years and has been widely used in process industry such as oil refining and chemical engineering. In previous work , through a simulation study we have demonstrated that MPC can improve the closed-loop performance of continuous tablet manufacturing process [1 , 2]. The implementation of the advanced control system to the pharmaceutical manufacturing plant is still a challenging task because of the different level of complexities involved (e.g. solid handling , irregular flow , sensing challenges , integration of control hardware and software). In this work , a hybrid MPC-PID control system has been implemented into a direct compaction continuous tablet manufacturing pilot-plant. The continuous feeders and blender are considered here as a demonstrative example. A PAT system is used to read the NIR spectral data at blender outlet and communicate it to the MVA (Multi-Variable Analysis) model performing PCA/PLS to provide the API concentration and RSD (relative standard deviation) value. These critical quality attributes (CQA’s) are used as inputs to the MPC in the Process Control System. The MPC uses the two CQA inputs to drive the feed ratio and the blender speed. The MPC output (feed ratio) gives the feeders flow rate set points which are tracked by slave PID controllers. The implemented control scheme utilizes synTQ to integrate DeltaV with an NIR analyzer and MVA model. Main challenges were the integration of multiple hardware/software platforms including Process Control System , NIR analyzer , Multi-Variable Analysis (MVA) software , Process Modeling Software , and Bus Technology. Results demonstrate enhanced performance of critical quality attributes (CQAs) under closed-loop control compared to open-loop operation , thus illustrating the potential of hybrid MPC-PID control system in improving pharmaceutical manufacturing operations. The objective of this presentation is two-fold: first to highlight the design and implementation of hybrid MPC-PID control system for a continuous tablet manufacturing process , and second to demonstrate the performance of the implemented control system.  References1.  Singh , R. , Ierapetritou , M. , Ramachandran , R. (2013). European Journal of Pharmaceutics and Biopharmaceutics , http://dx.doi.org/10.1016/j.ejpb.2013.02.019. 2.  Singh , R. , Ierapetritou , M. , Ramachandran , R. (2012). International Journal of Pharmaceutics , 438 (1-2) , 307-326.