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

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

Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20–21, 2014 Continuous Manufacturing Symposium

“…For example, an efficient and direct route to control of impurities is to design an organic synthesis route and chemical reactor so that impurities are not generated, which also reduces the complexity and demands of downstream separations processes as well as simplifying the control system design . As another example, a modest change in tank configurations can greatly suppress the effects of disturbances on the exiting material attributes and their effect on downstream unit operations . A research need is to develop both control strategies and design methods for specific new unit operations for continuous pharmaceutical manufacturing.…”

Special Issue “Feature Papers”

“…The first paper provides a review of computational models and methods, which have applications to the continuous manufacturing of solid dosage forms [9]. In the second paper, a strategy for optimal-averaging level control of storage tanks in continuous pharmaceutical manufacturing processes is developed and shown to strongly outperform conventional PI control via simulation studies [10].…”

New Biosorbent Materials: Selectivity and Bioengineering Insights

“…However, some changes in the symbols and the physical meanings differentiate the models and give other potential to the whole engineering part. Models are used everywhere for simulating any possible process [54][55][56][57][58][59][60][61][62][63][64][65][66]. The main models, which will be discussed in following, are the Freundlich, Langmuir, and Langmuir-Freundlich (L-F) equations.…”