(233n) Fault-Tolerant Control Design and Risk MAP Based Resiliency Analysis of Continuous Solid Dose Manufacturing
- Conference: AIChE Annual Meeting
- Year: 2016
- Proceeding: 2016 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Monday, November 14, 2016 - 3:15pm-5:45pm
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.
- Ierapetritou M, Muzzio F, Reklaitis G. Perspectives on the continuous manufacturing of powder-based pharmaceutical processes. AIChE Journal.2016;62:1846-1862.
- Lee SL, Oâ??Connor TF, Yang X, Cruz CN, Chatterjee S, Madurawe RD, Moore CMV, Xu LX, Woodcock J. Modernizing pharmaceutical manufacturing: from batch to continuous production. Journal of Pharmaceutical Innovation. 2015; 10:191-199.
- Buchholz S. Future manufacturing approaches in the chemical and pharmaceutical industry. Chemical Engineering and Processing. 2010; 49:993-995.
- Vervaet C, Remon JP. Continuous granulation in the pharmaceutical industry. Chemical Engineering Science. 2005; 60:3949-3957.
- Teng Y, Qiu Z, Wen H. Systematical approach of formulation and process development using roller compaction. European Journal of Pharmaceutics and Biopharmaceutics. 2009; 73:219-229.
- Singh R, Ierapetritou M, Ramachandran R. An engineering study on the enhanced control and operation of continuous manufacturing of pharmaceutical tablets via roller compaction. International Journal of Pharmaceutics. 2012; 438:307-326.
- Singh R, Sen M, Ierapetritou M, Ramachandran R. Integrated moving horizon-based dynamic real-time optimization and hybrid MPC-PID control of a direct compaction continuous tablet manufacturing process. Journal of Pharmaceutical Innovation. 2015; 10:233-253.
- Hsu SH, Reklaitis GV, Venkatasubramanian V. Modeling and control of roller compaction for pharmaceutical manufacturing. Part II: control system design. Journal of Pharmaceutical Innovation. 2010; 5:24-36.
- Morari M. Design of resilient processing plants III a general framework for the assessment of dynamic resilience. Chemical Engineering Science. 1983;38(11): 1881-1891.
- Hsu SH, Reklaitis GV, Venkatasubramanian V. Modeling and control of roller compaction for pharmaceutical manufacturing. Part I: process dynamics and control framework. Journal of Pharmaceutical Innovation. 2010; 5:14-23.