Relevance of regulatory constraints in designing pharmaceutical manufacturing processes: A case study on waste solvent recovery

Abstract

This work deals with the relevance of regulatory constraints on the outcome of process design in pharmaceutical manufacturing with a case study on waste solvent recovery. The role of the investigated process was to separate and purify tetrahydrofuran from an azeotropic mixture with water and methanol. As the technologies to overcome the distillation boundary, zeolite membrane, pressure swing, azeotropic distillation, and entrainer processes were considered as alternatives, and were modeled and evaluated with regard to economy, environmental impact, and environmental, health, and safety hazards. The target concentration of recovered solvent, which cannot be altered because of regulations, was imagined to be modifiable, and two design problems, initial and extended, were formulated. A type of pressure swing process that was found to be optimal in the extended problem was equal to or better than any of the optimal alternatives in the initial design problem. Remarkably, the net present value of this alternative was about 17% larger than the maximum in the initial design problem. These results confirmed quantitatively that the way in which regulatory constraints are taken into account makes a difference in the outcome and that the appropriate formulation of a design problem is critical for pharmaceutical manufacturing processes.