Producing drugs quickly with a portable device? This is what MIT researchers achieved, at the request of the US Department of Defense. The technologies developed to meet this requirement will revolutionise the pharmaceutical industry, and Jean-Christophe Monbaliu, researcher in organic chemistry at the University of Liège, took part in their development.

Imagine a portable production unit that can produce, in record time, thousands of drug doses in order to meet demand in conflict zones, during epidemics, or simply during a shortage. No, this is not the plot of an upcoming film. The pharmaceutical industry is about to undergo a major revolution for drug production, thanks to the efforts of a team of researchers from the Massachussetts Institute of Technology (MIT), where Jean-Christophe Monbaliu contributed as a postdoc. Working at the University of Liège since 2013 as an organic chemist, he created  the Center for Integrated Technology and Organic Synthesis (CiTOS). Ever since his PhD thesis, he has developed an interest in new ways to create matter. ‘What we currently use to produce pharmaceuticals, and what we have been using for centuries, are batch reactors,’ he explains. ‘These are macroscopic reactors, generally made of glass or metal, in which matter can be transformed – a typical example is the classic round-bottom glass flask found in laboratories. Images of this type of technology have been found dating as far back as Ancient Egypt.’ These macroscopic reactors, which we have been using for a long time, are inexpensive to maintain, and highly versatile since they are compatible with a wide range of chemical transformations. However, they also suffer from many drawbacks. ‘Using batch reactor processes often means having to manage of large inventories of chemical intermediates that may be toxic or explosive. As a result, the industrial risk is very high,’ adds Jean-Christophe Monbaliu. In addition, most of current drugs are manufactured according to multi-step processes, which accounts for long production times. In some cases, their production can take an entire year. As a result, this type of production is highly time, resource and workforce-demanding. Finally, the reactions taking place in batch reactors are not efficient. ‘The reaction does take place, but the reagent mix and heat transfer are not optimal,’ says Monbaliu. ‘Heat is transferred very slowly from the walls of the reactor to the reagents (or the other way around), which results in less successful reactions or contamination with side-products. This means that the drug produced at the end of the process has non-negligible variations in quality.’ In the case of reactions that produce heat, transferring the heat to the outside of the reactor can also be an issue. As the heat is not released from the reaction vessel, it accelerates the reaction, resulting in a runaway reaction which can eventually produce an explosion. 

A mobile unit for emergency situations

With the limits of macroscopic batch reactors in mind, Jean-Christophe Monbaliu started investigating other technologies to transform chemicals during his several postdocs (Ghent University, University of Florida and then Massachusetts Institute of Technology). More specifically, he focused his work on a technology called microfluidics and continuous-flow processes. ‘Unlike batch processes, continuous-flow processes use micro- or mesoreactors. It's all about size,’ explains the chemist. ‘With micro- or mesofluidics, the processes involve specific reactors that can come in various shapes, but they all have one thing in common: they are made of channels, 100 to 1000 micrometres in diameter, through which reagents flow.’ Another difference with batch reactors is that micro- and mesofluidic reactors are fed with a continuous flow of reagents. The transformation occurs in the channels through which the reagents flow. This technology offers great advantages for transforming matter, as the mixing efficiency is excellent, and mixtures of chemicals get homogeneous much quicker than in batch; it also allows for very efficient control of how reagents interact and how heat is transferred.