A systematic methodology for the design of continuous active pharmaceutical ingredient production processes

Continuous pharmaceutical manufacturing (CPM) has emerged as a powerful technology to obtain higher reaction yields and improved separation efficiencies, potentially leading to simplified process flowsheets, reduced total costs, lower environmental impacts, and safer and more flexible production. However, the change from batch-wise production towards continuous operation and the definition of flexible design spaces requires a high degree of process knowledge. Process Systems Engineering (PSE) offers multiple methods and tools which can assist in efficient knowledge acquisition, structuring and representation, as well as on how to employ this knowledge for process (re-)design. The aim of this paper is to introduce a methodology that systematically identifies already existing PSE methods and tools which can assist in the design of CPM processes. This methodology has been applied to a process for the production of an API developed by H. Lundbeck A/S, demonstrating the mentioned potential benefits that CPM can offer.