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New Serial Testing Pathway Enables Immediate Screening Claims for EUA Tests

NEW YORK – The US Food and Drug Administration on Wednesday expanded on a new streamlined pathway to allow developers to quickly obtain a screening claim for COVID-19 tests.

The pathway, which was first announced Tuesday, is expected to enable more widespread use of viral molecular and antigen tests to screen people without symptoms of SARS-CoV-2 infection.

Addressing test developers during a weekly town hall, Timothy Stenzel, director of the FDA's Office of In Vitro Diagnostics and Radiological Health, said that if an EUA point-of-care or over-the-counter antigen test has a positive predictive value above 80 percent in symptomatic people, it can be immediately authorized to screen asymptomatic people using a serial testing paradigm.

"A test currently authorized with at least 80 percent sensitivity/PPA or above, with the lower bound being 70 percent or greater, can seek this immediate change to a screening claim," Stenzel emphasized.

For example, if a test is already authorized for use at the point-of-care or for non-prescription over-the-counter home-use, developers can "add a screening claim on request, by agreeing to do this serial testing program and doing [a] post-market study," he said.

The screening claim should specify the interval of the serial testing, and developers would then be expected to perform a study following this design with asymptomatic people after beginning to sell the test for point-of-care or over-the-counter non-prescription screening use.

"When it comes to OTC use, we are anticipating most developers will choose to send, instead of a single test, two tests per package, using this pathway. They would instruct the user to test on day one and day two, or day one and day three, or day one and day four," Stenzel said. "We would be looking for confirmation that whatever specific scheme you call for for your serial testing is validated and shows adequate performance." This policy holds whether the test is already authorized for point-of-care or for OTC, he confirmed.

The FDA is anticipating that serial testing will bring unknown performance in an asymptomatic population up to an acceptable level, Stenzel said, but nevertheless will want to measure that for each EUA test, "to confirm that performance in an asymptomatic population reaches that 80 percent or more utilizing serial testing," he said.

As noted in a document posted online Tuesday called the "Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing," a post-authorization study should involve at least 20 positive asymptomatic individuals.

Existing over-the-counter testing templates for single-use tests are still available to developers as well, Stenzel noted.

He said that the agency is leveraging evidence of a test's strong performance in symptomatic patients combined with serial testing to "mitigate the risk of false results when testing asymptomatic individuals for the cases in which we have not reviewed the asymptomatic testing performance pre-market."

By way of background, Stenzel also noted that the FDA and other government agencies' programs — such as the National Institutes of Health's Rapid Acceleration of Diagnostics (RADx) — encouraged submission of antigen point of care tests and home-use tests as early as January 2020. This has resulted in 15 home-use antigen tests and a handful of molecular tests receiving EUA for point of care and home use.

In July, the FDA issued a template with recommendations to obtain EUA for a home-use prescription and OTC diagnostic tests, and in September the FDA emphasized that serial testing would be a path to improved sensitivity of tests in asymptomatic people.

Yet, "To date, we have received no formal EUA submission of a fixed serial testing plan showing that it is functioning," Stenzel said. "We hope that this new pathway and policy will accelerate the use of serial testing to reopen schools and workplaces and keep convalescent settings safe." 

The agency is basing the new pathway guidance in part on briefing pertaining to "a very well-designed, well-executed study," Stenzel said, that used serial testing of an EUA molecular test and antigen test.

Although the head-to-head comparison clearly showed that the antigen testing was significantly less sensitive than the molecular testing, Stenzel said, "it also demonstrated that a serial testing program for the antigen test significantly mitigated the risk of false negatives." This was "the first really firm, good evidence that we had and helped usher in this new policy."

Stenzel emphasized that the CLIA requirements are overseen by the Centers for Medicare and Medicaid Services, and the new pathway does not alter those requirements. However, home-use tests are not subject to CLIA requirements, he noted.

The new template is also not automatically changing any authorization, but rather it is providing a streamlined path for test developers seeking serial testing claims.

"In order for a test to be authorized for OTC or non-prescription use, such test needs to have previously shown asymptomatic screening data ... but now we are allowing that data for asymptomatic performance using screening to be revealed to us after authorization," Stenzel clarified.

The template provides an option for screening authorization prior to collecting data or submitting the validation for asymptomatic people, but the FDA still expects validation with symptomatic individuals as well as usability, user comprehension, and layperson-appropriate labeling for an OTC test, Stenzel said.

However, a developer that has already submitted that information does not need to submit more in order to have the test authorized for OTC, he added. "They can simply come in with a supplement or an amendment application asking to convert to OTC based on the serial testing program."

Finally, Stenzel noted that clinicians can continue to order tests as they see fit, and FDA is "not going to object to the off-label prescription use of those tests that don't have a screening claim," including the use of blanket prescriptions, except for tests that have been labeled as only for use in symptomatic individuals. The agency has already authorized approximately 20 tests with claims for screening of asymptomatic people.