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February 5, 2018


In Optimal campaigns in end-to-end continuous pharmaceuticals manufacturing. Part 2: Dynamic optimization (click here for 50 days of free access), the authors investigate theoretical optimal campaigns in a continuous process of pharmaceuticals production. The simulated process, inspired by a pilot plant previously tested at MIT, includes several reaction and separation steps to produce final tablets. This paper demonstrates the use of nonsmooth differential-algebraic equations (DAEs) framework for such optimal campaigns design.

The model developed in the first part of this series of papers (Optimal Campaigns in End-to-End Continuous Pharmaceuticals Manufacturing. Part 1: Nonsmooth Dynamic Modeling) is embedded in a dynamic optimization problem formulated as a hybrid discrete/continuous and nonsmooth problem. The authors enforce the quality constraints only on an interior epoch (on-spec), optimize its duration and then use a gradient-based optimization tool (IPOPT) to solve the problem. The on-specification productivity is considered over the entire campaign. Various control valves are chosen as decision variables, as well as the timings of the control switchings. The yield and the productivity of the process are considered as objectives under a constant (short) time horizon. Pareto curves of optimal yield and productivity for various campaign durations are calculated. The results show a significant improvement over a “nominal” operating procedure that only considers steady-state operation. This methodology can be used to guide decision makers, in both the design stage of new plants and the operation of existing configurations.