Where Are All the OTC Rapid Antigen Tests for COVID? FDA’s Role in Blocking These Tests from the American Market

November 19, 2021By Jeffrey K. Shapiro & Richard A. Lewis, Senior Regulatory Device & Biologics Expert

In England, over‑the‑counter (OTC) rapid antigen tests for COVID are widespread and available at low cost.  In America, these tests are scarce and relatively high‑priced.  Why is that?


Rapid tests for COVID-19 are fast, inexpensive to manufacture, and a relatively easy method to detect the presence of an active SARS‑CoV‑2 infection.  The tests are similar to a pregnancy test in the sense that they display one or two lines to indicate a result after a few minutes.

The tests are very accurate in detecting individuals with a relatively high viral load (symptomatic or not).  They generally have a high Positive Predictive Value (PPV), which means that when users test positive, there is a high likelihood that they are infected.  A positive result, however, is treated as a screen.  A follow up laboratory‑run molecular diagnostic (RT‑PCR) test is considered the gold standard for actual diagnosis.

On the minus side, a rapid antigen test may miss an infected individual with a low viral load (e.g., early in an infection).  Therefore, if a test is negative, the test‑taker is a presumptive negative, meaning that there has not yet been a rule out of SARS‑CoV‑2.  That is just another way of saying, however, that the rapid antigen tests are best positioned as a screening tool.

By law, a rapid antigen test may only be marketed after FDA grants an Emergency Use Authorization (EUA).  We have worked with dozens of clients trying to obtain an EUA for prescription and OTC rapid antigen tests.  Unfortunately, in these cases, FDA has acted less like a gatekeeper and more like a brick wall.

Unrealistic Performance Standard

A significant obstacle to approval of these tests is the performance standard that FDA applies.  As context, a rapid antigen test is uniformly evaluated by comparing the results to the RT‑PCR gold standard.  For OTC intended use, until very recently, FDA had been requiring 90% positive percent agreement (PPA) in detecting positive cases between the rapid antigen tests and RT‑PCR.

This threshold is unreasonable given the differences in the technology.  A rapid antigen test analyzes the sample as‑is, while the RT‑PCR can amplify the sample many times to create a detectable signal.  In the case of a person who is positive but with a low viral load, the RT‑PCR analytical instrument may detect it, while the rapid antigen test may be called incorrectly simply due to an incorrect visual reading by a lay user.  Despite this significant difference in technological characteristics and human factor impact, FDA’s 90% agreement requirement has effectively required rapid antigen tests to perform as though they were RT‑PCR tests, even for specimens with a low viral load.

FDA’s unreasonable requirement has excluded perfectly good rapid antigen tests from the American market.  These tests could have been a valuable screening tool for COVID during the past year or so.  True, these tests will never provide the same diagnostic quality results as RT‑PCR, nor will they perform as well in patients with a low viral load.  All things being equal, we would only need RT‑PCR tests.

But all things are not equal.  For one thing, there is limited laboratory capacity to test specimens.  This capacity limitation does not apply to OTC lateral flow antigen tests, which can be manufactured in the hundreds of millions per month at a much lower cost than RT‑PCR tests.  Additionally, the RT‑PCR tests generally require that a specimen be collected and mailed to a laboratory, creating at least a 2‑day turnaround.  They are not rapid.  In short, the low-cost OTC rapid antigen tests are not a replacement for RT‑PCR tests, but they provide a testing option better suited for mass screening.

On November 9, 2021, FDA lowered the threshold from 90% to 80% positive percent agreement for OTC rapid antigen tests.  Both of these thresholds appear to be arbitrary.  FDA has never publicly explained how it chose either threshold.

It would be sensible, given the inherent technological characteristics of rapid antigen tests, to avoid an overly high (and arbitrary) PPA threshold that many candidate tests will struggle to meet.  Sometimes, the ability to hit the threshold depends randomly on how many low viral load subjects enroll in a study.  That is not a real measure of the test performance, but rather, the luck of the draw.

An alternative would be to significantly lower the PPA threshold to a level that most rapid antigen tests, if they are performing correctly, can meet.  For instance, consider the blood tests that detect the antibodies produced by SARS‑CoV‑2 infection.  FDA only requires a PPA of 70% (when compared to RT‑PCR) for devices that detect IgM antibodies produced by a SARS-CoV-2 infection.  Why not apply this same threshold to rapid antigen tests?

Another alternative might be to allow a calculation of PPA limited to specimens exceeding a set minimum viral load.  That would exclude the low viral load specimens that all rapid antigen tests struggle with.  It also would help standardize the performance evaluation among the different tests by focusing on the viral load range that all of these tests should be able to handle well.

Or, perhaps FDA could eliminate the PPA threshold but require disclosure of a test’s performance in lay language on the outer box.  FDA has taken a similar approach to other devices like OTC blood glucose meters.

Any number of alternatives would be worth considering to escape the unsatisfactory status quo.  But what FDA must first do is to stop demanding near‑diagnostic quality results from OTC rapid antigen tests.  They need to be reviewed in a manner that is appropriate in light of their inherent technological characteristics and intended screening use.  Then, the other players in the healthcare system may determine whether the tool is right for this pandemic and how best to deploy it.

These players include the federal and state public health authorities, the healthcare profession, third party payors, and patients.  They all have a role to play, but right now they all are sitting on the sidelines because FDA has not let the OTC rapid antigen tests out of the locker room.

Not A Priority

FDA’s flawed review approach is compounded by its failure to make the review of these tests a priority.  To the contrary, FDA has strangled these tests with red tape and delays.

For example:

  • The EUAs for prescription and OTC rapid antigen tests can sit for months before FDA even assigns a reviewer. By its (in)action, FDA has strongly signaled that OTC rapid antigen tests are not a priority.
  • FDA requires companies to select RT‑PCR comparators for their clinical studies but refuses to publicly designate which ones are acceptable. We have had more than one client spend considerable time and money conducting a clinical study, only to be told that the comparator is not acceptable.
  • FDA recommends that the choice of comparator be discussed as part of a confidential pre‑EUA (PEUA) submission. Unfortunately, this option has been proven to be impractical.  Once submitted, PEUAs are reviewed in an unpredictable timeframe spanning anywhere from two months to never.  On average, our experience with PEUAs is closer to 6 months from submission to feedback.
  • During the EUA review process, FDA sets deadlines for responding to deficiencies that are impossible to meet. They can be as short as 24 to 48 hours.  Sometimes, FDA will issue a deficiency letter and, on the same day, close the file.  The sponsor must gather the requested information and cycle through with a brand new EUA filing.

When all is said and done, FDA’s review system does not efficiently process EUA submissions for OTC rapid antigen tests.  There is no sign that FDA understands what it has done wrong or that the agency is taking steps to fix it.

The Biden Administration announced almost a month ago that it hopes to streamline the review process.  Apparently, the National Institutes of Health (NIH) will spend $70 million on a new program to accelerate test-makers through FDA’s process. It was reported as follows:

HHS said in a statement that as part of the new program, government health experts will conduct studies on over-the-counter tests and work with the companies ‘to compile proper data, work towards the right benchmarks for performance and support other needs that will help ensure they are providing the best submissions possible for FDA’s regulatory review.

This statement is another way of saying that FDA has not been doing its job properly.  So now taxpayers will pony up $70 million for NIH to help companies navigate FDA’s flawed process.  It would be better if FDA were to fix the process itself.

This announcement also looks like it may be regulatory vaporware.  We have not seen any evidence of a stood‑up program.  FDA has not responded to our request for details and none have been publicized.  All we have so far is an announcement.

Needed Reforms

FDA should urgently initiate a rapid reboot of its current review of OTC rapid antigen tests.  The following quick reforms would go a long way:

  • Publish a list of acceptable RT‑PCR comparators (with the option to discuss other comparators in a PEUA). That would significantly facilitate clinical study design.
  • Significantly lower or eliminate the PPA requirement (or modify it to exclude low viral load subjects). Consider requiring disclosure of performance data in lay language on the outer box.
  • Remove deadlines for sponsors to respond to deficiencies. It costs FDA nothing to put an EUA file on inactive status rather than requiring a brand-new filing.

If these reforms (and others) were carried through, FDA would be in a better position to ensure that sponsors wishing to offer high quality OTC rapid antigen tests for COVID can readily do so.  Whether the other players in the American healthcare system would choose to use these tests is not guaranteed, but at least the option would be available.

Categories: Medical Devices