Lessons Learned in Developing a Manufacturing Facility for Flow Chemistry

Specific designs are necessary when installing manufacturing facilities for active pharmaceutical ingredient (API) plants, especially for scaling up manufacturing using flow chemistry. Each flow reactor is a device focused on an intended reaction. However, due to the required heat exchange (heating or cooling), the parts responsible for carrying out the reactions (the flow reactor itself) are often enclosed in a jacket or setup in a way that makes it difficult to verify the internal structure from the external view. In this paper, we present a case where a piping error made during the installation of a flow system, designed for oxidation reactions with heating, led to a subsequent manufacturing failure, as the error went undetected before operation was started. In retrospect, it would have been possible to identify the piping error ahead of starting manufacture, based on data, such as the internal pressures, obtained during the premanufacturing test. Specifically, the mistake highlighted the importance of identifying the flow lines with ″synchronized internal pressures″ and prediction of the flow lines where the internal pressure is expected to be at its highest or lowest. It is thought that our observations regarding the failure offer an example for OPR&D’s special issue on ‘Lessons Learned in Organic Process Chemistry’ and the details will be disclosed.