On Wednesday, the US Food and Drug Administration issued an emergency use authorization (EUA) to Cellex, a North Carolina pharmaceutical company, for a new finger-prick blood test that can detect an immune reaction to SARS-CoV-2. It’s not the first test to get this thumbs-up from the FDA: At least two dozen other tests that search for the virus’s genetic material on a throat swab have already received an EUA. But the Cellex test was the first for a blood test (a different company claimed that honor earlier in the week, but later retracted its claim).
There’s a curious caveat in the test’s labelling and marketing materials, though. The authorization, like those that came before, clearly states “This test has not been FDA cleared or approved.” So what does it mean to be authorized, but not approved?
In the context of the coronavirus pandemic, the FDA has been scrambling to update its regulations for companies that want to develop, manufacture, and distribute tests, aiming to balance the need for speed with concern for public safety—i.e., not releasing a test that tells people they’re not infected when they actually are. The most recent word came on March 16, which lays out the steps companies must follow to release tests. They’re fairly loose, especially compared with earlier versions of the regulations, which some claimed were delaying the deployment of tests.
In short, swab-based genetic tests, which are used to diagnose a current infection, can be marketed and used as soon as they perform well in an initial trial with relatively few samples—even before an EUA is issued. The company has to submit those trial results within 15 days of their completion, and if the FDA issues the EUA, nothing much changes: It just means the tests can continue to go out to labs and hospitals (no at-home tests are permitted yet). If the EUA is denied, the company must stop distributing the test and issue a recall. Companies are allowed to seek special exemptions to those steps from their state governments.
An authorization for these SARS-CoV-2 diagnostic tests differs from full-bore “approval” in two key ways.
First, the validation bar is much lower. FDA approval is a cumbersome, lengthy process that typically entails multiple human trials involving hundreds of participants—first to ensure that the product does no harm, and then to ensure that it actually works. For an EUA, a company essentially just has to show that the product works well enough in a trial with just a few dozen samples, getting the right answer at least 95% of the time for samples with a small viral load, and 100% of the time for higher viral loads and in samples that have no virus. The process can be completed within weeks, rather than months or years.
The second distinction has to do with duration. An EUA only applies for as long as the Secretary of Health and Human Services has made a public health emergency declaration, and only in the context of that particular emergency. An approval, by contrast, is permanent (barring the emergence of new data calling its safety or efficacy into question).
“It’s not perpetual approval to use this forever,” said Matthew Weinberg, CEO of the Weinberg Group pharmaceutical consultancy, a ProPharma group company. “FDA is allowing certain products that appear to have value in the Covid-19 crisis, without the complete set of trial data, to bring relief where they appear to bring relief.”
For blood tests like the one from Cellex, the bar is even lower: FDA is allowing those to be distributed without the need to ever even apply for an EUA. At least two dozen companies have told the FDA they’re going to do just that.
That’s a bit counterintuitive, since blood tests are known to be less accurate in diagnosing infection than swab tests. (They detect the bodies’ immune response to the virus, which can show up a number of days after SARS-CoV-2 takes hold in the body.) But FDA requires blood tests to include another caveat, informing users that the tests should not “be used as the sole basis to diagnose or exclude SARS-CoV-2 infection.” That caveat is still required for blood tests that receive an EUA.
The only reason to seek one, as Cellex did, is for the marketing advantage of calling your test “FDA authorized.”