3D Printing System Makes Drugs On Demand

Disintermediating pharmaceutical companies? JL

Robert Service reports in Science:

Interconnected reaction vessels carry out four different chemical reactions involving 12 separate steps, from filtering to evaporating different solutions. By adding different reagents and solvents at the right times and in a precise order, they were able to convert simple, widely available starting compounds into a muscle relaxant. “This approach will allow the on-demand production of chemicals and drugs that are in short supply, hard to make at big facilities, and allow customization to tailor them to the application,”
Forget those long lines at the pharmacy: Someday soon, you might be making your own medicines at home. That’s because researchers have 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. The work, they say, could digitize chemistry, allowing users to synthesize almost any compound anywhere in the world.
“It could become a milestone paper, a really seminal paper,” says Fraser Stoddart, a chemist and chemistry Nobel laureate at Northwestern University in Evanston, Illinois, who was not involved with the work. “This is one of those articles that has to make [people] sit up and take notice.”
3D printing already has a broad reach. It’s used to make everything from shoes and car parts to blood vessels and guns. In recent years, chemists in Australia and Europe have jumped into the fray, using the benchtop devices to create small-scale chemical reactors. But the reactors are designed to be integrated into manufacturing plants to improve their efficiency and safety, says Christian Hornung, a chemical engineer and 3D printing expert at CSIRO Manufacturing in Melbourne, Australia. 
But Leroy Cronin, a chemist at the University of Glasgow in the United Kingdom, was looking for a stand-alone device. He wanted to broaden the ability of nonspecialists to make drugs and other chemicals, in essence “democratizing” chemistry in much the same way MP3 players did for music, by turning songs into a digital code that can be played by any device with the right software.
Cronin’s first stab was a 2012 paper in Nature Chemistry in which he and his colleagues described something he called reactionware, 3D-printed chemical reaction vessels containing catalysts and other components needed to carry out specific reactions inside. By simply adding the starting compounds, Cronin’s team could synthesize a variety of simple compounds, including a ring-containing organic compound called ethylbenzene. At the time, however, Cronin says that critics doubted whether this approach would be useful for making more complex compounds, such as pharmaceuticals. “I like annoying people, scientifically,” he says. So, he pressed on.

A 3D-printed reactor makes medicines on demand.

Sergey S. Zalesskiy and Leroy Cronin

It appears the effort payed off. In today’s issue of Science, Cronin and his colleagues report printing a series of interconnected reaction vessels that carry out four different chemical reactions involving 12 separate steps, from filtering to evaporating different solutions. By adding different reagents and solvents at the right times and in a precise order, they were able to convert simple, widely available starting compounds into a muscle relaxant called baclofen. And by designing reactionware to carry out different chemical reactions with different reagents, they produced other medicines, including an anticonvulsant and a drug to fight ulcers and acid reflux.
So why not just buy a reactionware kit and scrap the printing? “This approach will allow the on-demand production of chemicals and drugs that are in short supply, hard to make at big facilities, and allow customization to tailor them to the application,” Cronin says. That could encourage the production of medicines used too rarely to justify conventional commercial production, as well as use in remote settings, such as on space missions, Hornung adds.
Cronin says that removing organic chemists from the mix is another one of his goals. These workers need to be present for most synthesis steps, and run the risk of being exposed to dangerous reagents in the process. “It will allow organic chemists to focus on creating new molecules,” he says. It could also let biologists and other nonspecialists easily create short-lived compounds on demand for their research, including fluorescently labeled compounds.
But 3D-printed reactionware could also lower the barriers to synthesizing dangerous drugs. That is “absolutely” a concern, Hornung says.
But Cronin argues that it shouldn’t prevent beneficial uses that could save many lives. One of those is that distributed chemical production could quash drug counterfeiting, a huge global problem in which drug manufacturers replace active pharmaceutical ingredients with inert or even dangerous compounds. Counterfeit drugs are estimated to make up as much as 30% of medicines in some developing countries and cost legitimate pharmaceutical companies up to $200 billion per year. Distributed chemical manufacturing, Cronin argues, could ensure that drugs are made as advertised, because each reactionware setup would only be able to produce a single medicine.
But it remains to be seen whether drug regulators will go along with a new way of making medicines. To do so, agencies like the U.S. Food and Drug Administration will need to rewrite their rules for validating the safety of medicines. Instead of signing off on the production facility and manufactured drug samples, regulators would have to validate that reactionware produces the desired medication. Cronin agrees it’s a hurdle. But he argues that future printed reactors could simply include a final module containing standard validation tests that produce a visual readout, much like a pregnancy test. “I think it’s manageable.”