By Paul Nicolaus
October 6, 2021 | The U.S. Food and Drug Administration (FDA) has fast-tracked tests under Emergency Use Authorization (EUA) during the coronavirus pandemic. Along the way, there has been a flurry of activity in a short time.
But what will happen to the many COVID-19 tests that have been issued EUAs once the public health emergency winds down? Diagnostics World gathered insight from the FDA and several companies to learn more about the road ahead.
Heightened EUA Activity
The increased level of EUA activity becomes apparent when looking back in time.
From about 2008 to 2020, FDA issued a total of roughly 60 EUAs to support preparedness for various declared public health emergencies, potential public health emergencies, or material threats such as H1N1, Ebola, and Zika, according to an FDA spokesperson. Some of those EUAs included multiple products, like the Swine Flu N95 EUA that authorized 15 models of N95 respirators.
By comparison, as of July 1, 2021, FDA had issued over 400 EUAs in response to the COVID-19 pandemic, most of which are still in effect. Some of these are umbrella EUAs, which can make numerous products available under one authorization. Respirators, ventilators, and ventilator accessories have been made available under single EUAs in this manner, for instance.
More than 800 total medical countermeasures have been made available under EUAs during COVID-19.
But what happens to the array of authorized devices once the public health emergency fades away?
An FDA FAQ resource geared toward EUAs during the COVID-19 pandemic indicates that information about the duration of an EUA can be found in the Emergency Use Authorization of Medical Products and Related Authorities and in sections 564(f) and 564(g)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
Product sponsors of devices authorized under an EUA are encouraged to pursue premarket submissions via the appropriate regulatory pathway (such as De Novo request, 510(k), or PMA) during the health emergency so that the product can remain on the market after the EUA runs out.
FDA does intend to issue guidance with recommendations to companies looking to transition from EUA to full authorization, and those seeking full marketing authorization are encouraged to come in as soon as possible.
EUAs are in effect until it is declared that the circumstances justifying the authorization of the emergency use of the product is terminated under Section 564(b)(2) of the Act or the EUA is revoked under Section 564(g) of the Act. One of the reasons an EUA could be revoked is because of an “adequate, approved, and available alternative” to a product.
This all begs the question: To what extent will companies with EUAs pursue full approval for their tests, and to what extent will they simply abandon those tests when the EUA runs out?
Many May Wind Up Abandoning Tests
The EUA process for COVID-19 tests was designed as a less expensive, fast-track alternative to the standard 510(k) submission requiring smaller clinical studies and documentation, explained Mark Fasciano, CEO of Rover Diagnostics, a Columbia University spin-out that is working on a low-cost, easy-to-use, point-of-care COVID-19 test that is currently pre-EUA.
“In principle, the FDA reasoned that post-market performance surveillance could help make up for the abbreviated application,” he told Diagnostics World.
Although much of the work that goes into the EUA submission can be used in a standard 510(k), the 510(k) does call for more extensive clinical studies, which can be the most costly part of an FDA submission. The burden tends to be even higher on POC and OTC devices, he said, which have to demonstrate not just efficacy on larger populations than the EUA but also ease of use with a bigger set of operators.
Many companies will face difficult decisions when considering whether the 510(k) is worthwhile from a business standpoint, especially as government funding like NIH’s RADx program ramps down. Smaller companies in particular tend to have less in the way of cash reserves to devote toward the sizable financial investment needed for 510(k) clinical trial, Fasciano added.
There are an array of economic factors involved in a company’s decision to either pursue FDA approval or not, according to Milan Patel, CEO of PathogenDX, a DNA-based diagnostic testing company that was issued an EUA this spring for its COVID-19 multiplexed viral diagnostic assay, dubbed DetectX-Rv.
On the input end, he explained, some of these economic drivers include people, materials, data reporting, analytical and clinical validation, regulatory support, and the total time devoted to responding to FDA questions and requirements.
Meanwhile, the output end is a function of factors like the market size and the number of competitors. It also depends whether the approval is for a use case and claims that are the same as other companies submitting or a use case and claims that provide a unique market position and may be seen as a high priority for public health in the eyes of the FDA.
In Patel’s opinion, “a lot of companies are probably not likely to pursue 510(k) approval.” Every company has to weigh the ROI on its own, but the effort and cost to achieve 510(k) have to be given serious consideration because of the various economic factors that come into play. Over the long term, COVID-19 alone is not a sustaining market, and many companies have received EUAs to date. Ultimately, “the cost of compliance could outweigh the benefit the company yields in the marketplace when the market is upside-down in the demand-supply equation.”
Luke T. Daum, Executive Vice President and Chief Scientific Officer of Longhorn Vaccines & Diagnostics, predicts that most biotech companies will wind up abandoning their EUA developed tests (when the EUA runs out) and pivot to other tests as the pandemic subsides. It’s a decision that “boils down to dollars and cents,” he said.
Dozens of companies submitted EUAs during the pandemic, but as the crisis subsides, many of the smaller ones are unable to generate the type of sales revenue that would justify the time, money, and resources that are associated with a full 510(k) submission. These submissions are both expensive and time-consuming, he explained. The work can be tedious from the lab perspective, and every product claim has to be supported by replicate and statistically significant data.
Back in 2010, in the face of H1N1-09, Longhorn Vaccines & Diagnostics faced a similar deliberation. The company represented one of several EUAs issued during that pandemic, and according to Daum, the company was required to perform 25 sample replicates across 30 days, amounting to hundreds of quantitative polymerase chain reactions (qPCR) for a single study. “This was a lot of hard work and effort at the lab bench,” he said, and the decision was made not to pursue an approval at that time “because we didn’t see a path to ongoing testing.”
Some companies that developed COVID-19 tests to generate income when their typical testing business dropped off may not seek full approval. Others, however, are more likely to pursue it. All major companies will seek full approval, Daum predicted, and smaller companies with a client base that is likely to continue providing COVID testing in a seasonal environment will probably seek approval, too.
“Full approval will require a new set of testing with higher standards,” he added. “There will be greater reporting and required updates as the virus continues to mutate.”
Why Some Plan to Pursue Approval
Ellume, an Australian-based diagnostics company, plans to pursue full FDA clearance for its COVID-19 Home Test.
“We believe COVID-19 is here to stay and that, as we adapt to the new normal of a world with COVID-19 in our communities, rapid antigen testing has an important role to play in minimizing the number of infections and overall morbidity,” CEO and Founder Sean Parsons said. “This will be increasingly true as medicines become available to treat COVID-19 and we seek to streamline the time from infection to diagnosis to treatment.”
While vaccines are a pivotal part of the overall COVID-19 response, he believes that in and of themselves, vaccines will not be enough to entirely blunt the harm done to communities. When it is technically feasible, multiplexed diagnostics for common respiratory viruses like COVID-19 can provide additional benefits like trimming the time to diagnosis or cutting the cost of diagnosis.
The company has been developing its home testing solutions for various diseases over the past decade, conducting clinical and consumer usability studies well before the coronavirus pandemic hit. When designing the Ellume Home COVID-19 Test, it was possible to apply the company’s existing core technology and build a test intended for consumers from the outset instead of retro-engineering an existing point-of-health test. Ellume is confident that its COVID-19 Home Test will meet the FDA’s requirements.
Another example of a company that has decided to pursue approval (for at least some of its tests) can be found in Ortho Clinical Diagnostics, which has developed several antibody tests and an antigen test. In all, the company has launched five COVID-19 diagnostic products that are available under EUA, according to Chief Innovation Officer Chockalingam Palaniappan.
Ortho Clinical Diagnostics is partnering with the Biomedical Advanced Research and Development Authority (BARDA), a U.S. Department of Health and Human Services (HHS) office, to fund the development and submission for FDA approval for the first three of its assays. This includes the VITROS Anti-SARS-CoV-2 IgG Qualitative Test, the VITROS Anti-SARS-CoV-2 Total Qualitative Test, and the VITROS SARS-CoV-2 Antigen Assay.
“Our plans are to submit for approvals for all three of these assays by the end of 2021,” he told Diagnostics World. The company is pursuing full approval because of the ongoing need for fast and accurate results sought by stakeholders such as researchers, health care teams, and government officials. Meanwhile, Ortho is “assessing the market need and the regulatory requirements” for its other two assays, the VITROS Anti-SARS-CoV-2 IgG Quantitative and the VITROS Anti-SARS-CoV-2 Total N Qualitative Test, which launched under EUA in July.
Because the pandemic is still a concern for now, the company indicated it is taking the initiative to go through the FDA’s approval process in anticipation that COVID tests will become a part of patients’ regular repertoire of testing even after the current crisis eases up.
There will be a point where it will be important to determine whether symptoms come from COVID-19 or other respiratory illnesses. “It is too early to tell how big of a market there will be for this,” Palaniappan added, “but we feel it is large enough to make this effort a priority for Ortho Clinical Diagnostics because every test is a life.”
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.