The Dial-a-Drug Machine

By Emily Waltz

Photo: MIT

In an engineering feat that could revolutionize the way we buy medicine, researchers have built a refrigerator-sized machine that can synthesize drugs on demand. The machine is capable of producing drugs start-to-finish—from chemical raw materials to consumable medicine—in hours. Its developers, engineers and scientists at MIT, revealed their design today in the journal Science.  


Photo: MIT

Would you like some Prozac with that?

“It’s a cutting edge piece of work that pushes the boundaries of what’s doable,” says Rainer Martin, a senior principle scientist at Roche Innovation Center Basel in Basel, Switzerland, who was not involved with the project. “It opens a lot of new avenues,” he says. Such a machine could enable hospitals and pharmacies to produce their own drugs. It could be moved to locations where demand for medicine suddenly surges, such as epicenters of disease outbreaks and natural disasters. It could also cut down on wasted drugs that expire before they’re consumed.

The machine marks a big leap from the status quo. In traditional pharmaceutical manufacturing, the many ingredients in a drug come from different sources, and are assembled in steps often at multiple locations. The products are made in batches, rather than continuously like commodity chemicals. As a result, supply chain interruptions are common, causing drug shortages. Even when things go well, a finished dose can take up to 12 months to make. 

“Maybe 50 years from now it will be the Keurig machine of medicines”—John Lewin, Johns Hopkins Hospital

The drug synthesizer brings together all the steps of pharmaceutical manufacturing into one miniaturized, continuous-flow machine. It consists of a network of reactors, separators, crystallizers, pressure regulators, valves, pumps, and tubes. The components are arranged in a modular design that can be reconfigured to produce different kinds of drugs. Raw chemical compounds, reagents, and solvents are added and heated at different steps in the process, pumped through the network, purified, and formulated into a dosage form. The whole system is controlled by the software tool LabVIEW and can be operated by a single person.

To get a pure, high quality drug—the kind that would pass regulatory standards—the process has to be tightly controlled. To that end, the system is equipped with various commercial sensors that measure temperature, pressure, flow, and chemical composition. An attenuated total reflection (ATR) Fourier Transform InfraRed (FTIR) spectrometer tracks in real time the chemical composition of the flow—how much starting material is gone, how much of the desired product is formed, and whether reactive intermediates are still floating around. In FTIR spectroscopy, many frequencies of light are shined on a sample in different combinations, and the amount of light absorbed each time is measured, yielding data on the sample’s composition. 

To demonstrate the machine’s range, the MIT team produced four pharmaceuticals: diphenhydramine hydrochloride (Benadryl), diazepam (Valium), fluoxetine hydrochloride (Prozac), and the local anesthetic lidocaine hydrochloride. The synthesizer pumped out hundreds to thousands of doses of each drug per day, in purities that would meet U.S. regulatory standards. Switching production from the simplest of the four drugs to the most complex takes about two hours.

So far MIT’s synthesizer can only produce medicines in liquid form. The team is pursuing miniaturization of the processes involved in formulating tablets, they said. The machine will also need a green light from regulators, of course. And there are a number of practical matters to address, such as how operators will dispose of byproducts and waste in remote locations. 

The project was funded by the Defense Advanced Research Projects Agency, or DARPA, which commissions research for the U.S. Department of Defense. From a defense perspective, a tool like this could provide a new means for being prepared for threats and disasters. “It’s a game changer,” says John Lewin, director of the critical care and surgery pharmacy at The Johns Hopkins Hospital in Baltimore. Lewin consulted with DARPA on MIT’s project but spoke with IEEE Spectrum from his personal perspective. “The Department of Defense can stockpile drugs for threats they know about. But there are threats they don’t know about and they can’t stockpile for that.” A flexible drug synthesizing platform like MIT’s could be a cost-effective means for preparing for disasters, he says.

The MIT team expects to shrink the size of their machine by 40 percent—to the size of a dishwasher—in the next year and enable it to process more complex molecules, says Klavs Jensen, a chemical engineer at MIT.    

“Maybe 50 years from now it will be the Keurig machine of medicines,” says Lewin. At MIT’s pace, it might not take that long

Created at: 2016-04-01 05:08:12

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