Flow: Advantages, Challenges and Implementation

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It appears that in this particular case the phrase “if you build it they will come,” meets more than we might be able to adjust to. Or does it? After reading a brief review from Krist Gernaey’s group at the Technical University of Denmark (Chimica Oggi or Chemistry Today 2013), I have seen relevant action over the last year on early adapters to the use of flow chemistry for new drug substances and API production, along with the implementation of Process Analytical Technology. With the FDA embracing flow technologies and processes, and International Conference on Harmonization (ICH) committees establishing guidelines, it appears as though everyone is getting on -board. Most people in the industry feel this is more than a risk based approach – it is where they want manufacturing to go in future endeavors.

Back to the article — Starts out with the clear advantages from green to smaller production footprint and jumps into how flow chemistry can benefit from standardizing some of the in-line and feedback analysis in real time and for feasibility information — clearly the two need to be coupled on any large scale production for which flow chemistry can shine. However, what I found most interesting is that the micro-reactor and micro-chemical processing isn’t for all types of chemistry, i.e. it’s not a catch all for all batch processes and scale can dictate choices and what to do — including the possibility of adding phase separation (membrane, liquid separators), trapping packed resins and backend purification — real downstream processing.

I have included a schematic from the article where micro-flow or lab-on-a-chip thinking can be used to obtain valuable information, both in the production of compounds but also where it can be scaled-out. Although not in all diagrams, the use of PAT and separation units is starting to gain foothold — academicians are publishing in-line innovations and multiple reactor set-ups, commercial vendors are fighting for space, and process chemists are particularly driving the critical assessment parameter data obtained in the PAT process. All of these are good and positive for the future of our chemistry, and once the dust settles on the thousands clamoring for the best flow publication, we will see a sustainable educated group globally.

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Added from the article of a phase separator — there are many innovations taking place today and several choices on integrating this piece of the flow puzzle to their work (Kinesis, Zaiput, etc.). Happy Reading!


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