Covid-19 has depleted stockpiles of essential medicines in the U.S., straining our supply chains and hobbling the treatment of critically ill patients. The government and pharmaceutical companies are already decades late in trying to fix this problem and so far their proposed solutions fall short. To prepare for the next crisis — and make no mistake, there will be a next crisis — we need an entirely new way to make lifesaving medicines.
Two technologies — synthetic biology and fermentation — offer a promising alternative to traditional manufacturing.
Supply chain failures are leading to unnecessary suffering. In May, the FDA reported shortages of drugs including paralytics, which are needed to safely and painlessly insert breathing tubes, and analgesics, which manage pain while patients are on ventilators. Demand for these drugs rose 213% from January to April; at the peak, order fill rates — the rate that orders are filled and shipped to hospitals — dropped to 37%.
This is an immediate problem, but not a new one. For decades, the U.S. has sourced the active ingredients for many drugs from other countries; 80% of manufacturers are outside the U.S. In the last four decades, more than 40% of drugs were sourced from nature, mostly small-molecule drugs derived from plants. Notable medicines include morphine (pain management from poppy), taxol (chemotherapy from the Pacific yew), scopolamine (motion sickness from nightshade), and artemisinin (malaria from sweet wormwood).
Medicinal crops are at high risk of natural disruptions like floods, droughts, fires, insects, and diseases. Many plants are grown in specific climates — and some, like the poppy, are only grown under specific licenses — which means that bad weather or an infestation can wipe out a huge swath of global supply. Why not just stockpile drugs or drug ingredients? Considering just how much medicine is needed, especially in the case of a global crisis, stockpiling is impractical, inflexible, and too expensive to work at scale.
The agriculture-based supply chains we rely on today are unpredictable, inefficient, fragile, and costly. They will only become more vulnerable to climate-related disasters and other global uncertainty, like geopolitical conflict. We need a new manufacturing solution that will give the U.S. control over the medicines we make, including how much, when, and where we make them.
Because of Covid-19, there is now bipartisan support to protect our drug supply chain. A bill proposed in the House of Representatives calls for measures that would diversify our pharmaceutical supply; the Trump administration is preparing an executive order that would require essential drugs to be made domestically. Policy changes are necessary, but the steps taken so far don’t fix the underlying problem: that our supply chains can’t respond to sudden changes in demand.
Synthetic biology and fermentation can. With today’s understanding of DNA and modern computational tools, we can bioengineer the ingredients for medicines like analgesics and anesthetics using plants as inspiration. The process involves identifying pieces of genetic code that produce medicinally beneficial molecules in plants, then replicating those molecules by inserting synthetic DNA into brewer’s yeast. Growing bioengineered yeast in large fermenters can lead to large-scale production of those highly valuable molecules. We are already using this process today for some drugs — and have been for years. When Eli Lilly put Humulin on the market in 1982, people were able to get insulin made from bacteria and yeast rather than extracted from the pancreases of pigs or cows.
This bio-based approach could eliminate the need to source active ingredients from agriculture, streamlining today’s fragmented and slow-moving supply chains. Fermentation takes days or weeks instead of months or years. It also solves the problem of latency. When raw materials are planted and grown, there is a delay of up to two years before they’re sold. That means yields are set far in advance, and there is no cost-effective way to increase supply when there is a pandemic, drought, or other unexpected event.
A bio-based manufacturing platform could produce enough active pharmaceutical ingredients, within the U.S. and on-demand, with the appropriate investment and a clear policy vision informed by the biotech community, including synthetic biology experts. Like the federal government’s push in energy and transportation over the last decade, there is an opportunity to advance the field of synthetic biology by building new technology and manufacturing infrastructure, providing research contracts and grants, and offering loans to startups.
Public-private partnerships will also be essential. Together, startups and research organizations can develop next-generation technologies, pharmaceutical companies can scale up manufacturing and distribution, and government agencies can create economic incentives for adoption.
At present, there’s little reason for pharmaceutical players to make sweeping changes. Government agencies could, however, motivate these players to adopt new practices that lead to more efficient, agile supply chains. Tax incentives — such as credits for reducing the use of land or toxic chemicals — could encourage fermentation-based manufacturing methods that don’t require farming. Public health care systems could also influence pharma companies by creating new drug procurement policies. They should prioritize buying medicines made via fermentation in cases where traditional alternatives are less efficient to produce and less responsive to changes in demand.
The government also plays a role in encouraging private investment in synthetic biology as a manufacturing platform. The first step is to minimize the regulatory risks and uncertainties associated with new technologies and methods. To encourage progress, it will be important for regulatory agencies to accelerate review and approval timelines for fermentation-derived medicines and the facilities involved in making them.
Today’s drug shortages are exacerbated by, but not isolated to, Covid-19. The next disruption is a question of time, and efforts to prevent or at least mitigate them must address fundamental supply chain problems. A synthetic-biology-based manufacturing platform offers a domestic, rapid-response, economical solution.
To save lives and protect our supply of essential medicines, we need to make bold bets on the next wave of technology and infrastructure. And we need to start today.
Christina Smolke is the CEO and co-founder of Antheia, a synthetic biology company based in Menlo Park, Calif., professor of bioengineering at Stanford University, and a member of the National Academies’ Committee on Science and Innovation Leadership for the 21st Century.
The Trump Administration is preparing to require certain essential drugs be made in the U.S. This, along with bringing supply chains back from overseas, are long overdue steps. I suppose we are finally getting around to address this because we have a president with an unconventional background for the presidency–business supply chain experience–quite an advantage when it came to emergency PPE and ventilator production and distribution.
That’s all well and good unless you take multiple meds a day and are allergic to yeast!
Personally, I find it helpful when experts and leaders write informative pieces like this — it seems that this often overlaps with the focus of their work, that doesn’t make it any less informative or an ad. Imagine if experts couldn’t write about the things they work on ….
Nice article, but this is an ad.
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