Method for reducing environmental, health, and safety risks in active pharmaceutical ingredient manufacturing based on multiobjective evaluation

This work presents a method for assessing and retrofitting the manufacturing processes of active pharmaceutical ingredients (API) considering the risks caused by the environment, health, and safety (EHS), as well as economic and technical aspects. This method consists of four steps: (1) process mass analysis, (2) EHS risk evaluation, (3) generation of improvement options, and (4) multiobjective evaluation and interpretation. A new indicator is proposed as a base for risk evaluation, which considers the dynamic change in process risks as well as the technical countermeasures in the process. The multiobjective evaluation supports the identification of promising improvement options regarding the risk-reducing potential of EHS, economic performance, and the efforts of change management according to Good Manufacturing Practice. A case study was performed in an industrial API manufacturing plant, which includes charging, reaction, filtration, extraction, crystallization, centrifugation, crystal-form conversion, crystallization, filtration, and drying. By following the method step by step, a promising option could be identified that could effectively reduce EHS risks with reasonable efforts in the economic and regulatory aspects.