Biologics, are currently manufactured at centralized facilities according to rigorous protocols, but such facilities require multiple years to design, build, and qualify and are just not suited to respond to rapid changes in demand. Furthermore, should a manufacturing facility go offline, perhaps because of a natural disaster, it is likely to result in severe shortages that would adversely impact public health – this happened in 2017 after Hurricane Maria hit
Puerto Rico.
Another huge issue in the industry today that should not be ignored is the fact that pharma suffers from enormous expenditures that, nonetheless, results in relatively few new drugs and therapies reaching the market. Novel enabling approaches, which eliminate practical development limitations and ultimately lower production costs, will be indispensable in meeting these challenges.
The Defense Advanced Research Projects Agency (DARPA) created a program to fund the development of Biologically-derived Medicines on Demand, called the Bio-MOD program – and I was fortunate to receive funding under this program. The program is primarily driven by a need for medicines in the battlefield and austere locations, but it also considers the factors mentioned above. The requirements of the program were to develop a technology that could manufacture biologics at the point-of-care in under 24 hours under GMP-like conditions.
It was a daunting challenge and my team and I quickly realized that we could not achieve this with conventional cell-culture based approaches – growing the cells alone would take longer than the specified period. Fortunately for us, the availability of cell-free expression technologies (also called in vitro translation or IVT) had evolved to the point where they could meet our needs. The Bio-MOD technology recently described by us combines IVT from cell lysates with microfluidic purification methods (1). The system used lyophilized Chinese Hamster Ovary (CHO) extracts, which meant that cold chain could be eliminated and allowed the system to be operated anywhere in the world, including on a remote battlefield. Highly purified protein products are produced in a few hours using an automated platform with built-in diagnostics to monitor process consistency. This manufacturing technology essentially reduces a large GMP facility to the size of a suitcase.
However, during the course of this work, I wondered if we could make it even simpler and cheaper to use. The use of cell-free systems meant that a large number of expression platforms was available, and perhaps human blood could be a viable source as well. We conducted a study in this area – and found that we were correct (2). While the initial yields are impractically low, further development will no doubt address this current limitation. Human blood may potentially involve fewer regulatory hurdles for use in humans, and could also allow for individuals to serve as their own source for the reagents to make their own medicine – and perhaps empower people who otherwise cannot readily access or afford biologics. We have been regularly meeting with regulators to ensure that we do not get too far ahead of ourselves, and the FDA Emerging Technology Team has been very helpful in providing us with guidance.
In my view, this is a new vision that can potentially create therapeutics not only for the point-of-care needs of prevalent diseases, but also for orphan diseases and rare conditions, which are often overlooked due to the smaller affected populations and the reduced profit margins. Bio-MOD technology combined with the use of human blood could also facilitate the fight against endemic diseases at remote and low-infrastructure areas by supplying the necessary therapeutics without the need for comprehensive and expensive development processes. In addition, colleagues working on long-duration space flight and manned missions to the Moon/Mars have also expressed an interest in the technology, as it solves the problem of biologics availability when transit times for delivery of supplies could be several months…
Finally, perhaps the ancient medical (and now largely discredited) practice of bloodletting might be re-purposed!
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References
- R Adiga et al., “Point-of-care production of therapeutic proteins of good-manufacturing-practice quality,” Nature Biomedical Engineering, 2, 675-686 (2018). D Burgenson, et al., “Rapid recombinant protein expression in cell-free extracts from human blood,” Sci. Rep., 8, Article number 9569 (2018).
