Many have acknowledged that the COVID19 pandemic was not a failure of our imagination – we’ve been preparing for such an event for decades by building biotechnologies for biosurveillance and medicines, conducting exercises, and stockpiling of medical supplies. Response to a spreading illness in many ways is not rocket science: treat the sick, protect the vulnerable, and stop the spread – mainly accomplished via the tools and products of biotechnology. Many are now asking, what could we have done better in the pandemic response? We would argue that our biotechnology tools and platforms for responding have not kept up with scientific advances – with the fortunate exception of the rapid development and delivery of a truly novel type of vaccine. That opportune success notwithstanding, much of our approach to preparing for a pandemic is outdated. The medical supply system has been optimized to reduce inventories and receive materials on a near ‘Just-in-Time’ basis. This has left very little surge capacity to respond to a global crisis, other than stockpiles of government owned materials which are not intended to cover all potential pandemics.
Earlier this year we described the “Fourth Industrial Revolution” in biotechnology, hallmarked by global competition between the US and China. In our recommendations for how to successfully grow the US bioeconomy, we recommended a focus on reshoring US production capacity, creating new state and local businesses focused on biomanufacturing, and expanding the use of bio-based products.[i] “Lessons learned” assessments applied in the post-COVID environment now offer a timely opportunity to apply these recommendations as we remedy U.S. biotechnology response capabilities; not only can we greatly improve our capability to respond in the future, but at the same time, we can prototype the modernization of our bio-industrial base.
Perhaps the best example of a static, antiquated response capability that typifies a lack of biotechnology modernization is the Strategic National Stockpile (SNS)[ii]. The word “stockpile” itself brings to mind cavernous warehouses in inconspicuous locations around the country, full of boxes, cartons, and pallets of emergency medical goods, slowly and inexorably approaching their expiration dates. Prior to COVID19, most Americans did not know of the existence of this strategic resource that the US had been investing in since its creation 1998. They quickly learned, through life-or-death media stories, that the stockpile may not have enough supplies to cover patients’ needs across the country.[iii] But as originally conceived, the SNS was never intended to supply the entire population of the US in a medical emergency, rather, it was created as a surge capacity: to set up transient medical field hospitals in individual public health emergencies, and provide a stop-gap, short-term back up to individual States’ stockpiles. Perhaps the most important, key feature of the stockpile is to house specialized medicines to protect against biological or chemical attacks against the US, such as the use of anthrax or nerve agents, requiring countermeasures that pharmaceutical companies would not produce otherwise.
Government responders were able to meet the demands on our vulnerable medical supply chains through massive feats of logistics. Large volume acquisitions from overseas suppliers,[iv] use of the Defense Department’s (DOD) stockpiles, and employment of the Defense Production Act[v] managed to meet needs at the height of the pandemic’s spread. While this worked, it is not the way we should handle the next pandemic crisis. This places the power to cut off supplies to the U.S. in hands of foreign governments and global markets - and depleting DOD’s stockpiles leaves the armed forces at a potential disadvantage in terms of medical readiness should a conflict arise.
We now have the opportunity to create a modernized biotechnology construct for the SNS more consistent with its original inception - one that features agility and flexibility, that could meet a broader range of threats that will have more diverse needs, and takes advantage of the biotechnology revolution already happening in the US economy. While the stockpile will still require the warehousing of emergency medical goods, it can also have a portion of its effort devoted to a more flexible and dynamic production capacity of bio-based essential materials.
A “Bio-based” Stockpile
Instead of building the SNS only with completed drugs, medical supplies, and standard active pharmaceutical ingredients (or ‘API’s’), the SNS could grow a “warm base” of biologically produced materials through the bioeconomy’s expanding biomanufacturing industry.[vi] By using the COVID experience as an exemplar, a thorough assessment of rate-limited raw supplies that were in need during the pandemic should be a starting point. Many companies are already producing these raw materials for everyday products as the bioeconomy grows in the US, so instead of building a parallel industrial base just for the SNS, public private partnerships could be created to leverage this existing commercial activity from established, successful biomanufacturing companies on an as-needed basis. By selecting contributors that are distributed throughout the US and establishing continuous minimum stockage levels of designated raw materials and in-place contracts for emergency execution, we would not only re-shore needed supplies and reduce dependence on foreign suppliers, but create a widespread, distributed model throughout the states that offers agility for response in just-in-time fashion. An additional benefit of developing a broad base of manufacturing capacity is the ability to overcome the historic challenge of manufacturing scale up. Rather than expecting one company to have a hundred-fold increase in production, the US can gain the same output through a coalition of companies, each increasing on a more realistic scale.
Some example products that might be worth pursuing are already evident. Modernized genome sequencing information could be connected to threats in real time as infectious diseases are monitored around the globe. RNA vaccine preparedness could be achieved by banking frozen DNA plasmids or mRNA vaccine prototypes based on regularly gathered genomic biosurveillance data, which could then be quickly spun up to design needed vaccines. This approach could also work for DNA- and RNA-coded antibody therapies. Because RNA extraction enzymes might be utilized by companies in the normal course of biomanufacturing, they could be utilized in surge capacity for emergency response needs in the creation of vaccines and antibody-based medicines. A full assessment could generate additional similar examples. This approach also provides the advantage of being threat-agnostic: by maintaining modular pieces that are adaptable, the SNS could more readily meet unanticipated biothreats as they emerge.
Furthermore, there are ample examples of raw materials for non-medical countermeasures. Resins, often produced overseas, are critical for production of syringes, needles, microfluidics, catheters, pipettes, moldings for manufacturing, intubation tubes, and many other supplies across all of healthcare. Materials such as polypropylene, and nitrile butadiene rubber could be created through biological manufacturing and re-shored to biomanufacturers here in the US. These foundational materials would be needed regardless of the type of biothreat, naturally occurring or man-made – so it also makes sense from the perspective of national biodefense.[vii] Bio-based resins not only offer greater diversity in their application to medical materials but also have advantages in how they may be reused, an advantage during a pandemic surge.[viii]
Importantly – the current way we try to “right-size” the SNS involves complicated calculations to determine not only what finished products should be purchased, manufactured, and stockpiled, but also the quantities of each. By supplementing this calculus with a raw materials-based approach that can be expanded and shaped on demand, some of this calculus can be simplified. By having stocks that are more flexible, they can be tailored and incorporated into the medical product needs for each threat as it arises. A feature of bio-based manufacturing is that biology grows, offering another advantage in addressing the expiry problem currently encountered with the SNS. By banking stored/frozen precursor organisms, we can simply grow some components of what is needed at the time of emergency.
Conclusion
A re-imagined, modernized stockpile could enable the US to more readily respond to health threats in real time. Incorporation of a warm base of biologically manufactured raw materials could be achieved through public/private agreements and engaged during emergencies to provide needed raw supplies for both medical and non-medical countermeasures. Advantages of such a strategy to US biodefense are many. The reshoring of basic biomedical supply chain components to the US would reduce dependency on foreign supplies in emergencies, while at the same time create a widespread, on demand flexible capability across the US (one that would also have the added benefit of creating quality jobs and strengthening the US bioeconomy). It would lessen the burden and cost of expensive drugs and supplies that might otherwise expire if not utilized, and alleviate the dis-incentive that many pharmaceutical companies have in committing their platforms for drugs that may never be used. Finally, and most importantly, this could offer greater flexibility and agility for medical countermeasures against a myriad of threats. If successful, this could serve as an innovative model shared with other countries as they set up their own stockpile capabilities, fortifying the US role in global health security. The current administration has signed an Executive Order[ix] to account for the sustainability of the public health supply chain, including an assessment of the SNS. Further, the National Academies of Sciences has taken on a project to assess how the US government makes critical decisions about while public health and medical countermeasures it pursues.[x] So now is the most opportune time, as we rebuild after the pandemic’s damage to the US economy.
Dr. Diane DiEuliis is the Assistant Director and a Senior Research Fellow, and Mr. Patrick Terrell is the Deputy Director, at the Center for the Study of Weapons of Mass Destruction, Institute for National Strategic Studies, at the National Defense University.
The views expressed in this op-ed are the authors’ own and do not reflect the official policy or position of NDU, the Department of Defense, or the U.S. government.
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