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Averaging Level Control to Reduce Off-Spec Material in a Continuous Pharmaceutical Pilot Plant

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Author(s): Richard Lakerveld | Brahim Benyahia | Patrick L. Heider | Haitao Zhang | Richard D. Braatz | Paul I. Barton

Journal: Processes
ISSN 2227-9717

Volume: 1;
Issue: 3;
Start page: 330;
Date: 2013;
Original page

Keywords: control | process modeling | process simulation | parameter estimation | dynamic modeling | optimization | crystallization | continuous pharmaceutical manufacturing

ABSTRACT
The judicious use of buffering capacity is important in the development of future continuous pharmaceutical manufacturing processes. The potential benefits are investigated of using optimal-averaging level control for tanks that have buffering capacity for a section of a continuous pharmaceutical pilot plant involving two crystallizers, a combined filtration and washing stage and a buffer tank. A closed-loop dynamic model is utilized to represent the experimental operation, with the relevant model parameters and initial conditions estimated from experimental data that contained a significant disturbance and a change in setpoint of a concentration control loop. The performance of conventional proportional-integral (PI) level controllers is compared with optimal-averaging level controllers. The aim is to reduce the production of off-spec material in a tubular reactor by minimizing the variations in the outlet flow rate of its upstream buffer tank. The results show a distinct difference in behavior, with the optimal-averaging level controllers strongly outperforming the PI controllers. In general, the results stress the importance of dynamic process modeling for the design of future continuous pharmaceutical processes.
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