Researchers at the University of Maryland, Baltimore County, have developed a suitcase-sized device that is poised to disprove the old adage that of fast, cheap and good, you can pick any two.

The device, named Biologically Derived Medicines on Demand (Bio-MOD), was able produce small batches of proteins of good manufacturing quality within a few hours.

For now, the third leg of the trifecta – cheap – is lacking. "Right now, the costs are much more [than cell culture-based biologics production], because the cell extract is still fairly exotic," Govind Rao told BioWorld.

But, ultimately, making proteins with the Bio-MOD technology could also be cheaper than producing them via cell culture systems. "The component cost," he said, "is not more than a laptop."

Rao is professor of chemical & biochemical engineering and director of the Center for Advanced Sensor Technology at the University of Maryland, and the senior author of the paper reporting the results in the July 9, 2018, online issue of Nature Biomedical Engineering.

Biologics have become a major class of therapeutics, but one whose cell-based manufacturing and cold-chain storage challenges and expenses are notorious.

The first version of the Bio-MOD system was developed in response to a Defense Advanced Research Projects Agency (DARPA) program of the same name. Together with a Pharmaceuticals on Demand (PoD) initiative, the goal of the Bio-MOD initiative is to do an end-run around logistics constraints that can hamstring getting medicines to battlefields and disaster areas through point-of-care manufacturing.

DARPA itself is not known for its cost sensitivity. But low cost, and the broad reach it translates into, is one of Rao's goals for his work.

His previous accomplishments include a $200-inclubator made partly out of cardboard that can help premature infants in low-resource settings.

For the Bio-MOD, he said, "the hope is to spark a DIY revolution... I want this to be growing organically in the hand of other researchers. That's the best way to shake out any new technologies."

At the same time, DIY needs to be done "with the kind of care that the regulatory authorities demand – that is why we engaged with them early."

"From a regulatory standpoint, it's very attractive to have a box that is agnostic to whatever you're making," he said.

Nevertheless, Rao and his team were well aware that "Bio-MOD technology would be likely to raise new regulatory questions in biologics manufacturing," they wrote in their paper. For that reason, "we engaged in early discussions with the Food and Drug Administration's Emerging Technology Team who provided us with guidance on the steps needed to ensure regulatory acceptance. These discussions provided the framework for the work described here."

The device that the team built was able to produce therapeutic proteins using cell-free lysates rather than cells, and purify those proteins to GMP standards. The system is also capable of certain post-translational modifications, though in practice its abilities are limited so far.

They then used the Bio-MOD for the automated end-to-end generation of several biologicals, and showed that those biologicals met GMP quality standards.

One of those molecules was granulocyte colony-stimulating factor (G-CSF), a therapeutic protein that is approved for the treatment of radiation sickness. In another recent paper, Rao and his team had also described the cell-free production of G-CSF as well as erythropoietin.

"Right now, what we have is a national stockpile that is stored by the CDC... for emergency use in the event of a radiation leak or a terrorist incident," Rao explained.

That stockpile needs to be renewed every two years, when its shelf-life expires. And if it does need to be used, getting it to the people who need it may face logistical issues.

Making G-CSF with the Bio-MOD, Rao said, will be at the point of in vivo preclinical testing "in a few months."

Long-term, the device could be a Swiss Army knife of sorts for the production of proteins in both emergency and low-resource settings.

Having a box that is agnostic to its product is attractive not just from a regulatory standpoint. In post-disaster settings, for example, one box could produce batches of different therapeutic proteins. After Hurricane Katrina, for example, insulin shortages were an issue for evacuees from New Orleans, where more than 10 percent of the population has diabetes. Bio-MODs whose primary function is to ensure a supply of G-CSF in the event of nuclear disaster could be used to produce insulin until supply chains could be re-established.

The simple production of small batches of proteins could also make it easier to test biomedical hypotheses.

Rao cautioned that the system is "not ready for antibodies right now," due to their size and complexity.

Ultimately, though, there is no reason to suspect that the system is incapable in principle of producing antibodies and other biologicals of their size and complexity. Even now, it can produce antibody fragments and a host of other molecules.

Right now, the need to develop a cell culture system that can produce a biological is one stumbling block to testing potential therapeutics. But Rao said that with a mature version of the Bio-MOD, it is possible to imagine that "a clinician who has a gleam in their eye" could easily produce small batches of proteins for biomedical research.