Just happened to be looking up some flow reactor information from Chemtrix — haven’t had the opportunity to come into contact with this group over the years, but I certainly have seen them in the news – collaborations and partnerships with universities and high-end chemical manufacturers…….this is a pretty long way of saying that I downloaded a white paper on Continuous Manufacturing: Producing more with less, which was written by Dr. Charlotte Wiles….and available for download.
I’m not going to reword the article but simply point out that it got me thinking that many of us were trained in the batch mode in school and this still stood true for most of my drug discovery career. Time to take a step back and realize that we have been and are currently in the midst of a paradigm shift in chemical development, one where it can be started at the early research stage.
Dr. Wiles spent the first part of the paper talking about conceptual thinking — how we have done it the past, and the mindset that is evolving in discussion with people willing to listen and invest in a change from batch to flow chemistry. Footprint, chemical efficiency, improved safety are the big ones — and can be drilled down to include (safety: low reactant hold-up, excellent thermal and mass transfer, reduced plant reactor size; Increased reaction control: Higher reaction selectivity – improved downstream isolation; Shorter development times – reduced time to market, reduced development costs, performance of the equipment. All of this set the stage but I wasn’t prepared to what I thought was the key point — as a medicinal chemist, we often develop multistep syntheses to target drug candidates with little thought on large scale mixing, temperature, heat of transfer and cost of goods — hey, the process chemists are going to change the method anyway — DOES IT HAVE TO BE THAT WAY? — As Charlotte politely banged me on the head with, NO — we can start these methods in the research and discovery phase so that the methods are transferred and companies don’t have to through bad money on good to redevelop the process. My med chem method may have a chance of actually being used if we are retrained in the way we approach it — change the instrumentation, not the chemistry! I can think of this hard earned synthetic strategies moving to wash, rinse and repeat.
Take a look at the full portfolio of chemitrix — small to pilot scale options and by all means read through the paper to detail the case studies leveraging how we are changing the way we do our chemisty in real time. Kudos Charlotte — keep paving the way.