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A novel manufacturing strategy based on continuous processing, integrated with online/inline monitoring tools, coupled with an advanced automatic feedback control system is highly desired for efficient Quality by Design (QbD)-based manufacturing of the next generation of pharmaceutical products with optimal consumption of time, space and resources. In this work, an advanced hybrid MPC-PID control system as well as a simpler PID controller for a direct compaction continuous tablet manufacturing process has been designed and implemented for a pilot-scale pharmaceutical process. An NIR sensor, an online NIR prediction tool, a PAT data management tool, an OPC communication protocol, a standard control platform and control hardware have been used to close the control loop. A systematic methodology to design and implement the control system has been also proposed. A control framework with features such as the option to run the plant in open-loop as well as in a closed-loop scenario has been developed. Furthermore, within the closed-loop scenario, options for a simpler PID, a dead time compensator (Smith predictor) as well as an advanced model predictive controller have been included. The feature to run the control strategy in simulation mode has been added to the control platform to facilitate virtual control system design and performance evaluation. Two case studies involving a direct compaction continuous tablet manufacturing process have been considered to demonstrate the closed-loop operation. Case Study 1 was completed at Rutgers University and constituted the use of a continuous cylindrical blender with a rotating screw. Case Study 2 was based on a continuous tumble mixer and was completed at the University of Puerto Rico-Mayaguez Campus (UPRM).

Many of the therapies for personalized medicine have few dosage options, and the successful translation of these therapies to the clinic is significantly dependent on the drug/formulation delivery platform. We have developed a lab-scale integrated system for microdosing of drug formulations with high accuracy and precision that is capable of feedback control. The designed modular drug dispensing system includes a microdispensing valve unit and is fully automated with a LabVIEWcontrolled computer interface. The designed system is capable of dispensing drug droplets with volumes ranging from nanoliters to microliters with high accuracy (relative standard deviation <1%). We have determined that the system is capable of accurate dosing and in-line real-time gravimetric control.