A Holistic System Approach
Andreas Haubrich, head Process Engineering Laboratory, deputy head Process Engineering, Sanofi-Avent
Flow processes have to be handled as a holistic system approach. Diverse applications of flow chemistry in pharmaceutical environment demonstrate the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting.
Introducing such a way of thinking early into a development pipeline can give significant simplification during the scale up. The increasing demand of material needed for the different stages of development phases can be reached efficiently and finally the building of a large-scale facility is straight forward.
Focusing the continuous flow approach to a late stage process or a large-scale manufacturing plant limits the opportunity significantly. At these stages stringent timelines often limit the opportunity to optimize the specific reaction process and to apply flow in a strategically impactful way.
In order to step in continuous flow earlier there is a need for cultural changes due to lack of training or education in this area. The entire processing sequence, considering reaction, quenching, work-up, extraction and purification etc. as part of the holistic design of the preparative route needs to be worked out differently. The ability to install real-time monitoring leads to rapid identification current process status and/or upcoming of trends/issues. Furthermore, the use of direct in-line purification and analytical techniques can be implemented, thus generating a more streamlined and information enriched reaction sequence.
As flow chemistry is not a plug and play technology a thoroughly process analysis, including each unit operation of a process, has to be performed to identify e.g. key cost driver’s and most challenging obstacles.
All this makes the interaction of different working disciplines – chemists, engineers, analysts, statisticians and many more necessary, in order to end in an overall economic beneficial process design. By installing interdisciplinary working teams this flow chemistry will be able to capture full benefits.