If your pill had a passport, it might get more stamps than your own. To make the drugs you rely on, the ingredients may have been manufactured in China and India, then combined together in Germany, and pass through a half-dozen other countries before arriving at your local pharmacy.
It’s really difficult to trace the path of any particular pill—even regulators struggle with this—but nearly all drugs are made in enormous batches, then divvied up and shipped around the world.
That’s not an inefficient method, but it has its downsides. Since the process takes a while, it can cause shortages when medicines are in high demand. The concentrations of ingredients or quality of the drug can fluctuate with each batch. It’s also easier for counterfeiters to slip potentially dangerous fakes into the existing system.
But a number of scientists and experts think that drugs be produced continuously, the way cars and electronics are made. To make continuous drug production more efficient and economical, a team of scientists from MIT has been working to improve the manufacturing technology. Their most recent machine, published in a study in the April 1 issue of Science, is about the size of a refrigerator and can produce hundreds of doses of a drug per day. The technology’s not yet perfect, but it might be enough to start to cause a tidal shift in the way our drugs are made.
The machine, which the researchers are calling “pharmacy on demand” or POD, relies on flow chemistry, in which a chemical reaction is performed continuously as pumps move the substance through a tube.
The best way to understand how this differs from batch production is to think of it like an oven baking a cake, says Timothy Jamison, a chemistry professor at MIT and one of the study authors. The batch method of production is like baking one cake at a time—you start with a raw cake and after a few hours, you end up with a cooked one. But flow chemistry enables you to make a continuous series of cakes, running each through an oven while they’re on a conveyor belt. With this technique, you have cakes at different stages of being cooked, and that allows you to make more cakes overall in the course of a day.
The POD starts with simple chemicals and mixtures that, through a series of reactions, can be distilled into the active ingredients in four common drugs: diphenhydramine hydrochloride (found in Benadryl and Dramamine), lidocaine hydrochloride (used in anti-itch creams), diazepam (a sedative used in Valium) and fluoxetine hydrochloride (an SSRI used in Prozac and its ilk).
Despite this sophistication, the POD has its limitations. Gases and liquids are much easier through the system, so if by accident a chemical reaction creates a solid, the whole system can get clogged, Jamison says. Right now, the POD can’t continuously complete the final steps to making a drug after synthesizing the active ingredient. It’s just too complex at the moment, he says. His team is working on those “downstream” (post-active ingredient) steps more efficient and continuous in future versions of the POD.
In theory, though, the same technology could be used to create dozens or hundreds of other drugs. To make drugs that are chemically more complex, the POD will need the capacity for more steps, which will take more time. The team is working to give the POD the capacity to make Ciprofloxacin, a common antibiotic, and the active ingredient contains a molecule that is slightly more complex than the drugs the POD currently generates.
The team will need to add more pumps and reactors and other pieces of technology, Jamison says. “[Cipro] is going to need more like four or five steps to make it instead of the three or so that we used for the paper. That doesn’t sound like a large increase, but the complexity does go up significantly as molecular target gets larger.”
Someday, even the most complex drugs could be made with the POD or something like it. Another team at MIT is working on a similar system, called BioMOD, that can generate biologic drugs, a complex array molecules that are typically about 800 times the size of small molecule drugs and can currently only be synthesized from living cells.
If something like the POD were brought to scale, it would be much more economical than the batch method—because of the small size of the machine, the electricity, and operating costs would simply cost pharma companies much less, and they wouldn’t have to ship ingredients across oceans to manufacture a complete drug.
So what’s stopping the pharma companies? It’s mostly the barrier of regulatory approval, Jamison says. “By necessity, for good reason, the U.S. Food and Drug Administration (FDA) is cautious about changing processes that are going to be making [drugs] that patients are going to take,” he says.
Officials at the FDA are enthusiastic about a shift towards continuous production—they’ve been pushing for it since 2004, officials told the Wall Street Journal last year, but pharma companies have been slow to adapt. But the shift is already happening; in early April, pharma giant Eli Lilly announced that it will devote $40 million towards continuous manufacturing in its facility in Ireland.
Once it catches on, pharma companies will probably use continuous drug production to manufacture drugs for an entire region or continent, Jamison predicts. Devices like the POD might even enable hospitals to generate pharmaceuticals for their patients, though that would require a lot of regulation.
But we’re not quite there yet—the POD is “the cutting edge of technology right now,” Jamison says. “And I would say this is inventor-level expertise required to operate it.”