Have you ever taken your old compact discs and converted them to MP3 files so you could listen to your favorite music on your laptop, or through a portable MP3 device that’s much smaller than an unwieldy portable CD player? Now, researchers from the University of Glasgow are working on a very similar process, but instead of music files, they are using a chemical-to-digital converter to digitize the process of drug manufacturing; a chemical MP3 player, if you will, that can 3D print pharmaceuticals on demand.
3D printing in the pharmaceutical field is a fascinating concept, though not a new one. But this ‘Spotify for chemistry’ concept is new: it’s the first time we’ve seen an approach to manufacturing pharmaceuticals using digital code. According to Science, the University of Glasgow team “tailored a 3D printer to synthesize pharmaceuticals and other chemicals from simple, widely available starting compounds fed into a series of water bottle–size reactors.”
A 3D printed reactor makes medicines on demand. [Image: Sergey S. Zalesskiy and Leroy Cronin]
The digital code is used by the 3D printer to make a portable factory, which can make the drug by adding chemicals in a pre-defined, fail-safe sequence, making it possible for users to synthesize nearly any compound. This new method could change the world of pharmaceuticals as we know it, as it could be used to significantly increase how many useful drugs are readily available, regardless of their patent-life, because they won’t need to be made in dedicated manufacturing facilities.
“This approach is a key step in the digitization of chemistry, and will allow the on demand production of chemicals and drugs that are in short supply, hard to make at big facilities, and allow customisation to tailor them to the application,” said Professor Leroy (Lee) Cronin, the University of Glasgow’s Regius Chair of Chemistry; he designed and developed the new approach. “We will also use this approach to make a ‘Spotify for chemistry’, allowing scientists to develop better code to make important chemicals.”
Professor Lee Cronin [Image: University of Glasgow]
Cronin and his team, with funding from the university’s complex chemistry initiative, the European Research Council, and the Engineering and Physical Sciences Research Council, described their method in a paper, titled “Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals,” and demonstrated the system’s potential by using it to produce muscle relaxer Baclofen, which can treat muscle symptoms like stiffness, spasm, and pain, caused by multiple sclerosis.
The abstract reads, “Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.”
3D printing can now create chemical reactors designed to build specific medicines. [Image: Warren Knower, Volare Photography]
Cronin’s first attempt to democratize chemistry was back in 2012, when he and his colleagues published a paper about what he referred to as reactionware – 3D printed chemical reaction vessels that contained catalysts and other components for carrying out specific reactions. His team could synthesize several simple compounds just by adding the starting components, but many thought that the method could never be used to make complex compounds like pharmaceuticals.
But he continued his work, and this paper explains how his team was able to 3D print several interconnected reaction vessels, or modules, on an Ultimaker 3D printer. The reaction vessels can complete four different chemical reactions when the proper solvents and reagents are added at the right time and in the right order – all you need is a simple instruction manual.
Cronin told Chemistry World, “The chemist now becomes a digital designer.”
The 3D printed plastic reactionware was used to produce muscle relaxer baclofen. [Image: Sergey S. Zalesskiy and Leroy Cronin]
According to the researchers, this new ability to 3D print drug factories on demand could help personalize drug delivery to individual patients’ needs, not to mention lower costs, increase what choices are available to doctors, and reduce the counterfeiting risk – each reactionware setup, in theory, would only be able to produce one type of medicine.
“Lots of compounds that are extremely important for chemistry, biology and medical science cost more than $1 million (£720,000) per mole. We’ve been starting to make kits for these and it cuts the cost dramatically,” Cronin explained.
However, regulation will be incredibly important if the process is commercialized, so people aren’t making dangerous narcotics in their kitchens.
Timothy Noël from the Eindhoven University of Technology said, “By connecting these vessels and following a simple protocol, basically a child can prepare pharmaceuticals.”
Agencies like the FDA would need to overhaul their rules for validating how safe medications are, and make sure that the reactionware is making the desired medication, instead of just validating manufactured drug samples and the production facilities. But Cronin believes it’s important to continue the work, as the potential benefits of 3D printing drug factories far outweigh the negatives. One idea he has is to include a final module with future printed reactors, which have standard validation tests that produce a visual readout at the end of the process, similar to pregnancy tests.
“I think it’s manageable,” Cronin said.
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[Source: University of Glasgow]