There didn’t seem to be cause for alarm when a letter laced with a fine white powder crossed Robert Stevens’ desk on Sept. 19, 2001. And several days later, when he turned up at a hospital disorientated and feverish in the middle of the night, no one made the connection between Stevens’ flu-like symptoms and the mysterious letter he ultimately passed around to other coworkers back at the office.
At first, doctors suspected the 63-year-old photojournalist who worked at a tabloid called the Sun in Florida had contracted meningitis. But after an infectious disease expert zoomed in on his spinal fluid with a microscope, the real and startling culprit revealed itself. On Oct. 4, Stevens was diagnosed with pulmonary anthrax and the next day, became the first person to die from anthrax poisoning in the U.S. in 25 years.
For most Americans, the anthrax attacks that unfolded over the next few weeks of 2001 — which ultimately killed five and sickened 17— were a tragic but fleeting footnote to a year already upended by the shock and horror of the Sept. 11 attacks. But for the American national security community, they were a mini-dress rehearsal for a larger nightmare scenario they could suddenly see crippling the nation one day. The key takeaway? We were not ready.
Anthrax, smallpox, Ebola, the plague — in the hands of terrorists, these pathogens could be weaponized. On top of that, an awareness grew that we were also vulnerable to natural hazards, like a fast-spreading deadly virus. With those threats crystalized in the minds of top defense officials, countering biological threats became a new priority. Within the next few years, the government threw more money at the problem, laying the groundwork for a series of initiatives that would eventually lead to the creation of the Biomedical Advanced Research and Development Authority (BARDA).
Launched in 2006, BARDA has spent much of its history as a little-known office buried inside the U.S. Department of Health and Human Services (HHS), aiding the development of various medical countermeasures for a range of chemical, nuclear, biological or viral threats. But once the coronavirus pandemic hit the U.S., BARDA’s efforts suddenly took center stage.
Although the country is now rounding into 2021 with coronavirus vaccines and a potential end to the pandemic in sight, BARDA isn’t planning to fade back into obscurity. With the need for pandemic preparedness heightened among industry and government, BARDA is looking to build on its momentum and track record of success to continue advancing the development of needed pharma products to protect the country from biological threats.
As it works to put the pandemic behind it, BARDA is sending out the call that it needs partners in pharma to keep up the fight.
Bridging the 'valley of death'
With anthrax fresh on the minds of defense officials, one of the original government projects that led to the creation of BARDA was an effort to procure enough vaccines to protect Americans from a biological attack.
In 2002, the Bush administration dropped an additional $4 billion into the country’s $633 million biodefense budget with the goal of procuring vaccines — particularly for smallpox and anthrax — for the national stockpile. Two years later, the initiative took on the name Project BioShield and included more than $5 billion in bait for the pharma industry to develop medical countermeasures such as a new anthrax vaccine.
Some of the agency’s stated goals
- Develop robust alternative skin and blood products
- Take viral hemorrhagic fevers off the table
- Bend the opioid epidemic curve
- Use novel approaches to combat antimicrobial resistance
America needed plans and supplies and importantly, we needed drugs. But they were the kind of drugs that have little to no market value until the worst-case scenario hits. The kind of drugs most pharma companies don’t see much value in making. So, Big Pharma didn’t bite.
At first, the government turned to smaller pharma companies, striking a deal to develop an anthrax vaccine with a now bankrupt company called VaxGen and then later with Emergent BioSolutions (which has since become one of BARDA’s biggest biodefense partners).
But there was another problem: Too many drugs were plummeting into what is often referred to as the “valley of death” — the space between drug discovery and the decision to commit resources for development.
“It goes back to the anthrax and smallpox vaccines,” explains Chris Stanley, the president and principal consultant at Harmony Consulting. “Billions were spent on those products, but there was no market. Not only that, they would have to turn over the drugs to the stockpile and then they would expire, so the government ended up with this excess inventory on their hands.”
Recognizing that pharma companies didn’t just need money — they needed a partner in the government to help usher needed products through the many phases of development, clinical trials and filing for regulatory approval — BARDA was created.
The goal was for BARDA to function more like a venture capital firm than a government office, providing funding to companies that have a solution in line with BARDA’s aim of developing medical countermeasures. Yet, to succeed at that mission, BARDA also positioned itself as a true partner in product development, providing not only funding but subject matter experts that could help steer pharma companies through the quagmire of bureaucracies related to product development — something it has pulled off while dealing with government entanglements of its own.
From the onset, funding issues hovered over the new agency. Although BARDA was given a multi-year war chest of $5.6 billion, The New York Times reported in 2011 that in its first four years, the office had only received — in total — about half of its original annual budget.
More money eventually came in and BARDA succeeded in acquiring vaccines for smallpox and anthrax. Over time, BARDA’s biological targets have also multiplied to include a number of emerging infectious diseases, pandemic influenza, nuclear threats like radiation poisoning and burns, and even the opioid epidemic.
To combat these threats, BARDA has expanded its weaponry of various countermeasures under a growing list of sub-offices such as the Division of Chemical, Biological, Radiological and Nuclear (CBRN) Medical Countermeasures, the Influenza and Emerging Infectious Disease Division and the Pharmaceutical Countermeasure Infrastructure Division.
Even before the pandemic, BARDA’s accomplishments were impressive. To date, the agency has helped bring 56 new products through the hoops of regulatory approvals.
But new crises throughout its history have revealed new challenges.
BARDA insiders have also emphasized that without ongoing manufacturing readiness, the country would not be prepared for an outbreak — whether it’s from a terrorist attack or a novel virus. In 2018, Joe Larsen, then the acting director of BARDA’s Division of CBRN Medical Countermeasures, warned an audience at the 13th Annual Non-Dilutive Funding Summit that the way the government was responding to viral threats — investing in clean-up rather than prevention — was not the best path forward.
“Responding to an emerging infectious disease event is not something that is easily done or responsibly done with supplemental funding from Congress,” he said. “If we had a few hundred million dollars a year to help prepare for these events, that might be a better approach than spending $9 billion responding to these events in an emergency, which is currently where we find ourselves in … We had hoped to move into a more thoughtful and pragmatic approach of trying to prepare for emerging infectious disease events, but we realize that is a hard political fight these days.”
Because vaccine manufacturers typically only want to produce enough product for the seasonal market, it is difficult to create extra capacity that would be available in the event of an emergency. But at the time, Larsen said that the agency had dedicated enough funds to ensure that America at least had capacity ready to produce 50 million doses of a vaccine within six months of the detection of a new pandemic virus. Yet, in order to stay ready, that capacity would need to be maintained.
And all of BARDA’s efforts to prepare the country for a viral pandemic were about to be put to the test.
The COVID crisis
Gary Disbrow, BARDA’s current director, admits that in the early days of the coronavirus pandemic he was a little nervous about the situation. But at the same time, Disbrow says the office was ready.
“I don’t think anyone understood the full extent of what the pandemic would be,” he says. “But because of H1N1 and Ebola, we had been in response-mode before. We understood what we needed to do.”
To get ahead of the curve of the fast-spreading new virus, BARDA launched a portal called CoronaWatch that allowed companies to submit information about its potential countermeasure and request a meeting with BARDA and its federal partners. To date, Disbrow says that the portal has received over 4,000 submissions.
BARDA also immediately established an incident manager to oversee the office’s coronavirus response and quickly turned to pharma for help, looking at vaccine and therapeutic platform technologies it had invested in for Ebola and H1N1 from companies such as Regeneron, Johnson & Johnson, Moderna, Merck and Sanofi.
The proof of this quick mobilization has been well on display. In the last year, the agency has become the most prolific government partner in pharma, making headline-stealing deals with a swath of major industry players. As one of the lead divisions involved in Operation Warp Speed — the government’s multi-agency effort to deliver 300 million doses of a coronavirus vaccine by Jan. 1, 2021 — BARDA has cultivated its partnerships with dozens of drugmakers to help push vaccines towards the finish line. BARDA has also propelled the development of needed therapeutics and diagnostics tools, and all told, has invested an astounding $17 billion into combatting COVID-19.
In many ways, the pandemic highlighted how BARDA has redefined what a government outfit can be. While moving fast and staying nimble, it has become the pandemic partner you want in your corner.
“When the chips are down, you call BARDA,” says Dr. James Cummings, president of Government and Public Health Solutions at ICON, a global clinical research organization, consulting firm and drug developer, that’s also a part of BARDA’s Clinical Studies Network.
The BARDA supply chain
There’s no company that knows what it’s like to team up with BARDA more than Emergent. Since becoming the sole source of the anthrax vaccine, Emergent has developed into one of the country’s top biodefense pharma companies with a portfolio that includes commercialized vaccines for cholera, smallpox and typhoid, an opioid overdose antidote, and therapeutics and vaccines for other viruses in the pipeline. But it’s Emergent’s molecule-to-market CDMO manufacturing services that have given it a starring role in the push to get Americans vaccines.
In 2009, Emergent poured tens of millions of dollars into renovating its Bayview facility in Baltimore, Maryland. A few years later, Emergent struck a deal with BARDA who co-funded an expansion at the facility so that it could be used for production in the event of a pandemic. This year, a BARDA task order leveraging that facility went into effect and it is now one of the country’s main manufacturing plants for coronavirus vaccines being developed by Johnson & Johnson and AstraZeneca.
“Our pandemic response is the manifestation of our journey to diversify our offerings in the public health arena and our longstanding relationship with BARDA to develop a variety of medical countermeasures,” Sean Kirk, Emergent’s executive vice president of Manufacturing and Technical Operations, says. “That’s where I’m sitting right now.”
The value of the coronavirus BARDA deals have been major for Emergent. BARDA’s vaccine-production task order for rapid domestic production is valued at $628 million through 2021, and in its third-quarter earnings statement this year, the company reported a record year-to-date performance of $972.4 million in total revenues.
According to Kirk, fulfilling its contracts this year has also strained the company in new ways, requiring many to work seven days a week. Kirk says he’s on the phone with government officials every day and is “fighting hard to maintain the strong choreography between materials supply, staffing, tech transfer and ramping up of candidates.”
For companies like Emergent, being a part of BARDA’s efforts to create a network of manufacturing capacity means that in a national emergency, other contracts might be set aside to fulfill the government’s needs.
“We ask for a lot,” Disbrow admits. “We need to have access to capacity at a moment’s notice.”
To help maintain the ability to provide end-to-end product development, BARDA has also laid the groundwork to quickly test needed products. In 2012, the agency established a Clinical Studies Network (CSN) to assist in the development of needed therapeutics, diagnostics or vaccines. The idea is to give BARDA access to pre-vetted companies it can rely on to help combat emerging threats.
ICON, which has a background in clinical trials for a number of vaccines, diagnostics and therapeutics, was picked as one of the original five companies to be a part of the CSN and re-established its contract with BARDA in October. To be a part of the CSN, Cummings says that companies have to show that they not only have the infrastructure and know-how, but that they are compliant with government regulations.
“It’s great to be a trusted partner,” Cummings says. “We’ve been continuously engaged with BARDA and stand at the ready to support them if the need arises.”
What’s in it for pharma
This year, BARDA’s flagship Industry Week event — which allows the office to make its pitch to potential industry partners — saw its highest ever attendance. Held in October, the annual event drew in 2,000 registrants — nearly twice as many as the year before. Although the event might have drawn a bigger crowd because it was held virtually, the increased attendance also indicates that more companies are looking to see how they can get a foot in the door at BARDA.
Given the wide variety of BARDA initiatives, contracts with the agency arise in numerous ways. But most of the time, pharma companies wait to see what kinds of technologies BARDA is looking for. Even though ICON is a part of the CSN, Cummings says that the company generally watches for BARDA announcements and puts in a proposal if the company can fulfill a need.
In more normal times, BARDA contracts are often born out of “Shark Tank”-like meetings.
To put the word out about projects it’s looking to fund, BARDA has created a broad agency announcement that is updated as priorities change.
“They’re trying to look in a crystal ball and see what the threats are and design countermeasures for them,” Stanley, who has consulted companies on over $1 billion worth of BARDA contracts, explains.
According to Disbrow, BARDA currently has 15 material threats identified, which now includes the SARS-CoV-2 virus, in need of medical countermeasures.
If a pharma company has a solution in the works that aligns with one of BARDA’s needs, it can submit a proposal to set up a “TechWatch” meeting. During these meetings, Stanley says that companies typically get 30-60 minutes to make their pitch and explain how much the development of their product will cost.
Usually the TechWatch meetings are with division heads from BARDA and other agencies in case the product would be a good fit for different government initiatives. And generally, BARDA is on the hunt for something that’s not just useful, but is cutting edge.
“These are very geeky, incredibly intelligent people who want Star Trekkian technology,” Stanley says.
If BARDA’s interest is piqued during a TechWatch meeting, it invites companies to then submit a white paper or 10-page technical summary. If BARDA then wants to move forward, it asks companies for a full proposal, which Stanley says is an exhausting document to create that includes hundreds of pages with sophisticated cost modeling. Given the time and expense involved in both writing and reviewing full proposals, BARDA doesn’t usually ask for one unless the project is likely to result in a contract.
From beginning to end, Stanley says the process usually takes four to six months. However, contracts have been approved at a much more rapid clip during the pandemic and in some cases were awarded in as little as nine days.
For up-and-coming companies, a contract with BARDA can be a game-changer — not just because of the funds but also because of the access companies get to needed expertise.
“On the interior, they have just about every piece of what a pharma company has,” Cummings says. “They have experts in preclinical, clinical and manufacturing at the table. And so all of these people can take a look at the entire life-span of a product’s development and get those solutions across the threshold.”
BARDA’s expertise in commercialization also makes it unique in the world of government partners.
“Many of their employees are industry people, so they know what it’s like to navigate the challenges of product development,” Kirk says.
Being hooked up with BARDA also means that companies are engaged with other government agencies.
“Generally at tech proposals, there are folks there from other agencies so that they can get a clear signal about the product you want to develop,” Cummings says. “BARDA is a gathering point of other agencies, as well as a great standalone agency. I think that’s a neat feature.”
This inter-agency approach also helps position BARDA as a type of regulatory consultant for its partners. If, for example, the drug in development is headed for the strategic national stockpile, BARDA will provide the expertise needed to file for an emergency use authorization or approval with the U.S. Food and Drug Administration.
“BARDA has regulatory experts who work with the companies,” Disbrow explains. “They have pharma experience and come from the FDA. So we know what the FDA is looking for, and our experts work with companies to review their documents so that they are of the highest quality, which reduces questions we might get back.”
Kirk also emphasizes that working with BARDA goes towards a greater good.
“The thing I love most about them is that they are working in great service to our nation,” Kirk says. “They are busting their butts every day to make a difference.”
BARDA’s next missions
“We still need therapeutics to treat those that are severely ill,” Disbrow says of the ongoing COVID-19 pandemic, while emphasizing that BARDA’s work in that arena isn’t done. “For the next several months, there are going to be large numbers of people who will become ill.”
This year’s coronavirus outbreak won’t be the last pandemic to cripple the world. So, even while BARDA still wrestles with COVID-19, its experts are keeping their eyes fixed on how to better prepare for other emerging threats.
Although it might be tempting to develop a product that may score a major government contract — an approach that Stanley has seen some companies attempt — BARDA aims to back products that have some commercial value and customers outside of the U.S. government.
“In the early days, BARDA would be more willing to develop products specifically for medical countermeasures,” Stanley explains. “These days, BARDA won’t accept any product that doesn’t have its own commercial market.”
In other words, BARDA prefers not to be a company’s sole purchaser of its product.
It’s a tricky proposition for some drugs that fall into the medical countermeasures category, especially when it comes to preparing for an outbreak that may or may not come. Yet, one way to balance that risk/reward scenario for pharma companies is to develop flexible platforms.
“We’re looking at investments…beyond the ‘one drug, one bug’ to platform technologies,” Disbrow says. “We want proven technologies that can switch to the pathogen of interest so that we don’t have to switch technologies.”
Overall, taking the lessons of COVID-19 and applying them to future planning is likely to be a prime focus for BARDA.
“Looking forward, I’m positive there’ll be a huge push for pandemic preparedness,” Stanley says.
This year, BARDA launched its Division of Research Innovation and Ventures (DRIVe). The new division will use venture-style equity financing to invest in breakthrough technologies aimed at fortifying health security while recycling returns from successful ventures. So far, DRIVe has funded 25 companies with $30.7 million.
Advanced manufacturing technologies and therapies
BARDA likes the latest gadgets and, much like the FDA, is likely to continue backing advanced manufacturing technologies in pharma. In particular, Stanley says they are likely looking for any technologies that could radically increase capacity or quality. In pharma manufacturing, Stanley says those kinds of technologies might include automated plants, modular manufacturing, rapid manufacturing or advancements in purification.
At Industry Week, government officials and representatives from BARDA divisions also spelled out some of their other goals for 2021, including the need for advancements in genomic sequencing, which can be used to help identify disease risks, novel antibiotics to combat microbial resistance, faster platforms for vaccine production, new therapies for Ebola and pre-symptomatic diagnostic tools.
Although BARDA picks its contracts based on technology rather than politics, lawmakers pushing to onshore generic drug production could again turn to BARDA to help the country procure drugs needed in public health emergencies. In the spring, BARDA struck a major deal potentially worth up to $812 million with Phlow Corp., a startup in Virginia, to manufacture generic drugs for the strategic reserve.
The deal raised eyebrows in the generics space because it was perceived that there were no bids on the contract. However, Disbrow says that Phlow presented at a CoronaWatch meeting and applied through BARDA’s broad agency announcement, which includes funding opportunities for advanced manufacturing technologies. According to Disbrow, what made Phlow’s proposition alluring was its commitment to using end-to-end continuous manufacturing.
“The company was willing to invest in advanced manufacturing and new technologies that the FDA supports,” Disbrow says.
Although Disbrow couldn’t say if BARDA is likely to make other major deals to spur domestic generic drug production, the political will to continue pushing for the onshoring of generics isn’t likely to let up.
“I’m curious to see if the mission of BARDA will expand to include production capacity for essential medicines,” says Bowman Cox, an analyst with Informa Pharma Intelligence. “Because [successfully onshoring] will take more than the deal with Phlow. And there seems to be a lot of willingness to put more public money into this sector.”
Disbrow agrees that there is momentum for more onshoring on both sides of the political aisle.
“The pandemic highlighted supply chain issues,” he says. “It is only going to continue to stress the system as we move into large-scale vaccine manufacturing.”
The Strategic National Stockpile
Although the Strategic National Stockpile (SNS) is officially managed by BARDA’s parent organization, the Office of the Assistant Secretary for Preparedness and Response (ASPR), BARDA plays a key role in maintaining the country’s reserve of critical supplies by supporting the development and procurement of needed drugs.
But the COVID-19 pandemic revealed shortcomings of the nation’s reserves for drugs and medical supplies.
In May, the Trump administration announced the “SNS 2.0” initiative designed to better maintain supplies for the pandemic, and improve management and distribution. HHS and ASPR then sent a request for input to pharma stakeholders looking for feedback on how the agencies could achieve certain goals for the SNS such as ensuring there is better coverage for pandemics, bolstering domestic manufacturing of needed products, and improving real-time supply chain visibility.
Going forward, the government has set the stage to partner more closely with pharma to create a next-generation SNS with stronger digital capabilities to track movement in the pharma supply chain.
One tool that could be more broadly implemented is a supply chain “control tower” that was used this spring to track shipments of critical drugs.
“Pharma distributors would be able to share information so the government can get a clear view of how the supply chain is evolving,” Cox says.
And while agencies that play a hand in controlling the SNS look for ways to revamp the system, Cox says that there is likely to be a general push to increase inventories throughout the pharma supply chain.
“In the years leading to the pandemic…manufacturers pushed just-in-time delivery,” he explains. “If you have a global enterprise and you’re trying to hit financial targets, one way to keep improving profitability is to whittle down inventory.”
In light of the shortages experienced during the pandemic, Cox says that this philosophy is likely to shift.
“When the pandemic hit, manufacturers that had been doing a poor job of whittling down inventories were suddenly being celebrated,” he says.
Show BARDA the money
Of course, BARDA’s ability to move any initiative forward remains reliant on its budget. For fiscal year 2021, BARDA’s requested budget was $1.4 billion — a similar figure to years past. The massive influx of cash in 2020 that allowed BARDA to strike major deals related to the coronavirus came from supplemental Congressional funding. For now, it remains to be seen if Congress will pad BARDA’s wallet again in 2021.
“We are hopeful we’ll receive supplemental funding,” Disbrow says. “I think Congress knows that BARDA is doing a heavy lift right now. And we hope they see that it’s a good investment. We deliver on what we say we’re going to do.”
With whatever funding BARDA gets, Disbrow says that the agency will continue to work with its current pharma partners and hunt for more as it focuses on teaming up with the industry to protect the country.
“We need to find situations that are a win-win for both parties,” he says. “That is key to moving forward and forging those strong partnerships. Because if they succeed, we succeed.”