Combined simulation–optimization methodology to reduce the environmental impact of pharmaceutical processes: application to the production of Penicillin V

In this work, we present a systematic method for the optimal design of pharmaceutical manufacturing processes that allows decision-makers to assess economic and environmental concerns in the early stages of the process development. Our approach relies on the combined use of process simulation, multi-objective optimization, economic analysis and life cycle assessment. The pharmaceutical production plant design is mathematically formulated as a multi-objective mixed-integer dynamic optimization (moMIDO) problem, which is solved by a decomposition algorithm that generates as output a set of Pareto optimal solutions. The capabilities of the proposed methodology are illustrated through the production of the antibiotic Penicillin V.