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Processes 2013, 1(3), 330-348; doi:10.3390/pr1030330
Article

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

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Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA Current address: Department of Process & Energy, Delft University of Technology, Delft 2628, The Netherlands. Current address: Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK.
* Author to whom correspondence should be addressed.
Received: 13 September 2013 / Revised: 26 October 2013 / Accepted: 25 November 2013 / Published: 29 November 2013
(This article belongs to the Special Issue Feature Papers)
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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.
Keywords: control; process modeling; process simulation; parameter estimation; dynamic modeling; optimization; crystallization; continuous pharmaceutical manufacturing control; process modeling; process simulation; parameter estimation; dynamic modeling; optimization; crystallization; continuous pharmaceutical manufacturing
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Lakerveld, R.; Benyahia, B.; Heider, P.L.; Zhang, H.; Braatz, R.D.; Barton, P.I. Averaging Level Control to Reduce Off-Spec Material in a Continuous Pharmaceutical Pilot Plant. Processes 2013, 1, 330-348.

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