The year is 2021, and a new highly drug-resistant bacteria has been discovered. University labs have quickly developed a countermeasure, but the government’s contract manufacturers can’t produce it in time before the superbug is estimated to cross borders and spread globally. In response, national health officials are waiting to make the decision to activate the Watchtower system just after midnight. Manufacturing plants blink to life across the country during the night as staff sleepily pull themselves out of bed and pour a coffee to go. No bigger than a refrigerator, the plants had been spread around the country to guard against situations just like this. Specifications and protocols download to the plants, and technicians load the raw materials and begin production within hours. By 5PM the first batches are ready for distribution, and the outbreak is contained in time to stop it from becoming an epidemic.
This sounds like the premise for a Michael Crichton novel, and of course it’s 100% fictional. This year in our blog, we’ve covered exciting cutting-edge technologies like continuous manufacturing and 3D printing that could revolutionize pharmaceutical production – and manufacturing more widely – as we know it. In the near future, though, the scenario above might well go from speculative fiction to concrete reality.
Most innovations in manufacturing focus on the efficient allocation of personnel, raw materials, and physical space to reduce costs and waste, but this post is about something else entirely – a mobile plant requiring investment and maintenance an order of magnitude less than a traditional manufacturing facility. MIT researchers working with industry specialists have developed a prototype drug manufacturing plant as small as the size of a vending machine, and recently published their findings in Science. The prototype has already been used to produce liquid oral and topical solutions on-demand, and it eventually may be able to make vaccines, tablets, and pills as well.
Seeing a huge upside in the technology, DARPA provides funding for the project, which NPR explains could be used in “field hospitals for troops, hard-to-reach areas to help combat a disease outbreak, or…dropped at strategic spots across the U.S.” The prototype can already produce 1,000 doses in 24 hours, a shocking figure when you consider that’s faster than some traditional production plants. Several USP-standard products have already been produced, including the antihistamine diphenhydramine, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride. “If there was an emergency you could have these little plants located all over. You just turn them on and you start turning out different pharmaceuticals that are needed,” says Allan Myerson, MIT professor of chemical engineering and a leader on the project.
Instead of using a traditional batch process, MIT’s machine can continuously synthesize and compound molecules in a rapid, continuous chain. “We had to figure out new ways to make molecules, new ways to think about making molecules but from my perspective that has also provided us with a lot of opportunities that are very powerful,” says Tim Jamison, a chemistry professor at MIT also associated with the project. This could mitigate some of the limitations of batch chemistry, as explained in the Nature paper:
“Production of a finished dosage form can require up to a total of 12 months, with large inventories of intermediates at several stages. This enormous space-time demand …has led to increased interest in continuous manufacturing of APIs and drug products, as well as in the development of integrated processes that would manufacture the drug product from raw materials in a single end-to-end process.”
In addition to limiting the required capital expenses for a production facility, the continuous process would also drastically reduce the amount of storage space required to house finished product, intermediate forms, and the raw material and safety stocks. In 2011 the industry saw a slew of drug shortages including cancer and heart disease treatments among others. In most cases, drug shortages typically stem from:
- Failure of manufacturing to fully comply with GMP.
- A shortage of the active pharmaceutical ingredient (API).
MIT’s machine won’t create APIs whole cloth, but it could potentially provide a short-term source of GMP production. This technology could also help alleviate regulatory issues regarding niche generic drugs which while established and cheap to make, may have such low profit margins that companies will not allocate their limited production capacity to make them.
However, some in the industry do have concerns about the device.
Intellectual property rights and exclusivity are jealously guarded by companies, which have invested hundreds of millions of dollars developing a treatment. Safeguards would need to be developed to ensure any digital schematics, formulas, and SOPs are securely stored.
Physical security would also be a concern to guard against counterfeiting or unauthorized use. Since the devices are being designed for use in hospitals, clinics, and other secure facilities, this may not be a widespread issue.
Inventory management will be critical so that proper storage spaces for any APIs, buffers, and other raw materials would be in-place. Careful planning around safety stock, shelf life, and other concerns will need to be properly managed.
Although this prototype technology is in its infancy, researchers are quickly making breakthroughs and forging a path forward. As regulatory agencies grapple with its implications and embrace its capabilities, we should see exciting developments as the industry becomes more nimble, cost-effective, and responsive.