Eco-efficiency Analysis for Intensified Production of an Active Pharmaceutical Ingredient: A Case Study

This article presents results on cost and performance benefit analysis of optimization and intensification activities of a pharmaceutical process. A batch process for the production of a low-volume, high-value active pharmaceutical ingredient, developed at Sanofi (France), has been used as a case study. With the scale of 100 kg/y and a product price of a few thousands Euros per kilogram, also following a general trend in pharmaceutical industry, this process is supposed to be an ideal candidate for continuous, modular plant production of a highly potent drug. It was aimed to keep the information gathered generic, i.e. to stand for the whole class of similarly produced drugs. The impact of various chemical process parameters on the overall production costs has been investigated and process performance represented in terms of operation time, waste, and resource usage as the main process metrics. Five optimized and intensified scenarios were compared to the reference case operated at a Sanofi site: intensified reaction, continuous processing, alternative catalysts, change of solvent, change in the purification sequence, recovery of the key product, and intensified drying option. The analysis has shown that, under the assumptions used, an intensified millireactor-based process with a subsequent continuous postprocessing brings the most benefits in terms of cost, while its process performance, although equal or slightly better than batch, still can be optimized. The total product cost is then reduced by 35%, while the operating time is 27% lower than the base case, with 47% less labor needed compared to that for the reference case. First studies on ecological impact by the University of Jena confirm these promising findings and are outlined hereinwith its own paper on the respective details to follow. The results are now undergoing experimental validation in the newly developed compact container plant of Evonik.