Multiobjective Retrofitting Methodology for Manufacturing Processes of Active Pharmaceutical Ingredients Considering Environment, Health and Safety Risks

摘要

In the manufacturing processes of pharmaceutical active ingredients (APIs), huge amount of chemicals are used per unit amount of product, and the consequential risks need to be considered. This work presents a method for retrofitting API manufacturing processes considering risks of environment, health and safety (EHS) as well as economic and technical aspects. The method consists of four steps: (I) process mass analysis, (II) EHS risk evaluation, (III) generation of improvement options, and (IV) multiobjective evaluation and interpretation. Case study was performed on an industrial manufacturing plant of an API, which includes reaction, extraction, crystallization and centrifugation, and involves variety of process chemicals. By following the method step-by-step, a promising option could be identified which can effectively reduce EHS risks with reasonable efforts in the economic and regulatory aspects.