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
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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.
Lakerveld R, Benyahia B, Heider PL, Zhang H, Braatz RD, Barton PI. Averaging Level Control to Reduce Off-Spec Material in a Continuous Pharmaceutical Pilot Plant. Processes. 2013; 1(3):330-348.
Lakerveld, Richard; Benyahia, Brahim; Heider, Patrick L.; Zhang, Haitao; Braatz, Richard D.; Barton, Paul I. 2013. "Averaging Level Control to Reduce Off-Spec Material in a Continuous Pharmaceutical Pilot Plant." Processes 1, no. 3: 330-348.