(233n) Fault-Tolerant Control Design and Risk MAP Based Resiliency Analysis of Continuous Solid Dose Manufacturing

The recent development and adoption of continuous manufacturing technologies in pharmaceutical industries^1-3 has also created the demand for more efficient process monitoring and control techniques. This is particularly the case with solid dose manufacturing processes, in which unit operations, such as blending, milling, etc., that in a classic batch processing are performed sequentially, are now integrated with a higher degree of automation, and operated at steady state with less manual intervention.^4-8 It has also become apparent that fast and reliable control strategy design is a requirement for successful continuous manufacturing technology. Hence, in this study, a systematic framework for fault-tolerant control design and resiliency analysis is proposed for continuous solid dose manufacturing processes based on risk mapping, accessing, and planning (Risk MAP).⁹

First, a risk mapping was designed to characterize the frequency and severity of the potential faults during the design and operation stages, e.g., model-plant mismatch, calibration errors, failing/missing sensors, process disturbances, etc. The three levels of hierarchical control strategies design, which ranges from single proportional-integral-derivate (PID) control loop to plant-wide advanced model predictive control (MPC), were then assessed subject to the potential faults by using control key performance indices (KPIs), such as, time to product (T2P), magnitude to product (M2P), and other control measures, such as Morariâ??s resiliency index (MRI).¹⁰ Mitigation planning for severe faults were also suggested, e.g., to activate or decommission a specific control level, or to divert the off-spec products.

The proposed systematic framework for fault-tolerant control design was demonstrated in a pilot plant for continuous dry granulation process¹¹ and was shown to be efficient and robust in handling potential faults and achieving a robust processing line for solid dose.

References

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