President Biden has requested $81.7 billion for pandemic preparedness over the next 5 years for the Department of Health and Human Services. If the government invested at that rate every year for 100 years and were able to stop one COVID-19 sized pandemic at the current cost to the U.S. economy of between $10 and $22 trillion, that would be a 10x return on investment. But it is often difficult to understand the difference between federal investments: in this post, I’ll break down the funding designated for ASPR, the Office of the Assistant Secretary for Preparedness and Response. ASPR is only receiving $40 billion of the request:
Of the rest, $28 billion would go to CDC to strengthen public health infrastructure and early warning capabilities. $12.1 billion would go to NIH for basic research. And $1.6 billion to the FDA to streamline regulatory infrastructure.
But the ASPR investments are likely the most valuable: the tech and infrastructure outlined in this request will be America’s best shot at preventing the next outbreak from becoming a pandemic. The following are copy-and-pasted headlines from the budget and then our explanations of what they actually mean for pandemic preparedness.
ASPR was created following Hurricane Katrina to prevent, prepare for, and respond to public health emergencies. A team at ASPR called PHEMCE (Public Health Emergency Medical Countermeasures Enterprise) is responsible for deciding what countermeasures are needed. ASPR then has divisions to research and develop the countermeasures (BARDA), actually buy them (OAMCG), and ensure everyone is prepared (OEM).
The FY 2023 President’s Budget requests $40,019,000,000 in new mandatory funding for ASPR, available through FY 2027, to prepare for pandemics and other biological threats. This will require Congress to commit to giving ASPR $40 billion over the next five years for the programs outlined below.
End-to-End Advanced Development of Vaccines and Therapeutics Against High Priority Viral Families ($12.0 billion):
The budget sets aside $12 billion for ASPR to create vaccines for different viral families. Moderna designed a COVID-19 vaccine within days because researchers had spent 15+ years studying its sister and cousin, the viruses that cause SARS and MERS. Scientists knew exactly what part of the virus to use for the vaccine and even how to change it to make it work better. Unfortunately, we don’t have this deep familiarity with most of the other types of virus families.
There are 26 distinct "viral families” that are known to infect people. While humans share about half their DNA with bananas, some of these viruses share none of their genetic material with each other. Many don’t even use the same kind of genetic material — some use DNA and some use RNA, so copying their genomes is fundamentally different. Since viral families can be so different, scientists need to study and prepare vaccines against each one individually. Creating proto-vaccines will help prepare for a future outbreak, as it will likely be from one of these 26 viral families (but it will also help improve our ability to create vaccines in general).
ASPR would like to create proto-vaccines that can be quickly modified and deployed against any virus. The goal is to get from one “end” — where we are now — to the actual “end” — fully developed, approved, and maybe even produced. In practice, ASPR may pursue full FDA authorization for some vaccines against common pathogens. At a minimum, vaccine developers can get a prototype vaccine all the way through Phase 2 studies, where they can show that the human immune system does respond to a vaccine and make sure the vaccine is safe, without needing a pathogen. Once there is an outbreak of a new pathogen, the prototype can be given to people immediately. Vaccine developers can also update the prototype and get it to people within 100 days.
Viruses often bring only a small set of their own tools to copy themselves and steal the host’s own molecular machines. This can make broad-spectrum antivirals harder to develop than broad-spectrum antibiotics — there are fewer potential targets, and many of them are unique to a viral family.
However, the biggest issue with developing broad-spectrum antivirals is that people haven’t really tried. The general paradigm has always been “one virus, one drug.” There hasn’t been an incentive to do better — it’s more work, so why bother?
A broad-spectrum antiviral requires intentionally targeting common parts of the virus, such as the RNA-dependent RNA polymerases. Humans copy DNA into RNA, but not RNA into RNA, so RNA viruses bring their own tool to do that. Alternatively, it can require testing a drug against a bunch of different viruses rather than just optimizing for one or targeting common parts of the human system that responds to viruses.
The budget proposes a similar approach for drugs, directing the ASPR to implement “end-to-end development” of therapeutics or biologics in order to save time during a pandemic.
Preventing infection is better than treating it, but it’s important to have more than one strategy for combating a new virus. Having more than one strategy is a strong theme of this budget request. For that reason, the budget directs “Capital investments in vaccine production capacity” and “warm surge capacity” for the manufacturing of vaccines, vials, and syringes/needles.
Capital Investments in Vaccine Production Capacity and for Warm Surge Capacity for Manufacturing Vaccines, Vials, and Syringes/Needles ($15.0 billion):
If the U.S. wants a vaccine ASAP, companies don’t have time to waste hiring and training workers, building a factory, or acquiring supplies in the middle of a pandemic.
But it’s also not useful to have vaccine factories sitting empty waiting for an emergency. That would be a waste of resources and also might hinder a response if they aren’t actually in working order. This request would create factories and put them to work. Additionally, new vaccine tech is easier to adapt for different pathogens, but it’s not clear it’ll work for every pathogen. The old vaccine tech involved growing the virus, or parts of the virus, in vats, purifying it without letting it fall apart, and then injecting it into people. The new vaccine tech works by creating instructions for human cells to make parts of the pathogen. This is closer to what actually happens during an infection — the human cells make the antigen. But it’s possible that the old tech, especially if it’s improved, could still be important. The proposal is to not only make new vaccine factories that use the new tech but also improve the tech.
When the next pandemic comes, everyone will need the same supplies. By investing in all the pieces necessary to create and administer vaccines, the U.S. can ensure that it has some but also increase the supply globally.
Warm Surge Capacity for PPE and Diagnostic Tests ($4.0 billion):
The same idea for vaccine making translates to making personal protective equipment (think masks and filtration suits) and diagnostic tests (like rapid antigen tests or the stuff needed to run PCR tests) in the United States. The big issue is that it’s just cheaper to make this equipment overseas: this funding would help offset that cost differential.
Refill and Modernize Depleted Pandemic Stockpiles ($3.0 billion):
Remember all those masks, syringes, and equipment to help people breathe that were in the strategic national stockpile? The U.S. now needs to replace the disposables that were used and do maintenance on the equipment.
Advanced Development of Diagnostics and Technologies for Advanced Biosurveillance and Early Warning, including Pathogen-Agnostic Clinical and Environmental Surveillance Technologies ($1.5 billion):
The faster public health officials can detect a new outbreak, the faster they can respond. Advanced biosurveillance and early warning systems are critical for stopping an outbreak before it becomes a pandemic. Government officials need to know where and when to send out supplies or request physical distancing. They also need to know what the threat looks like so scientists can start fine-tuning and producing vaccines or treatments.
“Pathogen agnostic” surveillance means any pathogen can be detected — no one needs to know what it looks like ahead of time. Most of these technologies use the fact that all known pathogens have nucleic acid genomes (either DNA or RNA — the NA stands for “nucleic acid”).
Scientists can take a clinical sample (like spit from a person in a hospital) or an environmental sample (like sewage) and sequence (i.e., read) all the nucleic acids in it. The best part is that scientists don’t need to know what they’re looking for ahead of time — anything that’s growing exponentially can sound the alarm.
Advances in technology don’t need to be restricted to hospitals and labs. Imagine if you woke up feeling congested and could check quickly at home if you had COVID or RSV or the flu or a rhinovirus or if it’s just allergies. Tests could also be quick and cheap enough to check everyone as they get off an international flight.
Technology and Manufacturing for New Vaccine Administration Tools ($1.5 Billion):
Imagine being able to get a vaccine without a needle. It could be as simple as applying a band-aid. This would be great because 1. No one likes needles (and more than a quarter of adults have a phobia about injections) 2. They might not require a trained professional to administer. Today, this would make it easier to vaccinate people in countries that lack sufficient medical professionals, which is critical for ending a global pandemic. In the future, it might be important for getting people vaccinated when a highly transmissible pathogen prevents us from all crowding into a convention center to receive jabs.
Capital Investments in Active Pharmaceutical Ingredient (API) Manufacturing and Innovative Manufacturing Processes ($1.4 billion):
Drugs are currently made via batch manufacturing by having large machines in different rooms or at different manufacturing plants. In one room, the ingredients get weighed. Then someone comes and moves them to a room to be mixed. They often then require heating and purification before being pressed into tablets. That’s not generally how manufacturing works — most factories use “continuous” manufacturing methods where the product is carried along a conveyor belt while being transformed and packaged.
The budget endorses “distributed” manufacturing and sets aside $1.4 billion for investments in manufacturing techniques. In contrast to centralized manufacturing, decentralized manufacturing can produce drug ingredients closer to where they’re needed or in an area far enough from a disaster to be safe. The best part is that these innovative manufacturing processes can make more than one drug and be small enough to be shipped where they are needed.
Next-Generation PPE ($1.0 billion):
Both surgical and N95 masks are made of nonwoven fabrics, in particular melt-blown fabric, which is reminiscent of cotton candy. Nonwoven fabrics are cheaper, which is great for disposable PPE, and the fiber size and density can be controlled to make a breathable filter. The budget directs one billion dollars to investments in these fabrics and their manufacturing.
Some fabrics have antimicrobial additives, which kill viruses or bacteria either on the surface of the material or as they pass through. Unfortunately, most of these antimicrobial fabrics are woven and not cheap or breathable. But there’s no fundamental reason they can’t be, there just hasn’t been enough investment in the technology and fabrication. Better than just investing in the tech, the funds will also be used to get this next-generation PPE into hospitals.
Workforce Expansion Activities ($180 million)
All of these programs will create jobs. As equity is an important component of the Biden administration’s agenda, this budget item is designed to diversify the biomanufacturing workforce. The budget sets aside a relatively small amount of funding for job training programs “to recruit and develop skilled professionals for the biomanufacturing industry.” There are actually more people working in pharmaceutical manufacturing without any college degree (30%) than those with master’s degrees or higher (28%). The largest share of workers has a bachelor’s degree (35%).
If the U.S. wants domestic manufacturing of biologics, it needs to make sure there are enough workers. This doesn’t mean recruiting more people with graduate degrees. By providing targeted training and opportunities, the government can tap into a larger group of workers who would be a great fit for these roles that they may not have otherwise envisioned themselves doing.
This is an equity issue: if government investment will create new jobs, everyone should have an opportunity to fill them. But it’s also necessary for preventing the next pandemic: the U.S. needs a strong biomanufacturing workforce and that can’t happen without effectively using every resource.
Manage the Mission within ASPR ($439 million)
Someone needs to actually make sure that all the above tasks get done. This group will not only ensure the money is spent on the highest priority needs. Mission control will ensure that efforts are not duplicated and it’ll keep track of where the money is going (“transparent reporting”).
“Transfer authority” is a technical term. Currently, HHS has the authority to transfer money from one appropriations-defined money bucket to another. Right now, it can increase any bucket by up to 3%. So, if $2 billion was appropriated to BARDA for the year, HHS could take $60M from NIH (which received $45 billion this year) and give it to BARDA. The Biden administration has requested the transfer authority be increased to 10%.
It’s hard to predict exactly what the best use of funds will be in advance. Transfer authority will let Mission Control determine, at least at the margin, what the best use of the funds will be to prevent the next pandemic.
This $40 billion will develop the modern tools that we need to fight the next pandemic. Yes, the United States needs a stronger public health system, but we’ve seen how quickly that can fail. The U.S. needs a robust solution. What’s more American than pulling some new technology off the shelf and using it as an efficient shortcut to actually achieving the outcome we want? The modern tools outlined above are more tractable and efficient, especially if they receive investment now. By devoting current resources to pandemic-fighting technologies, future Americans won’t have to go through the same exhausting exercise we went through with the COVID-19 pandemic. The better tools we have in advance, the more efficient our response will be — saving money, time, lives, and a lot of work.