FDA Clears the Way for Serial Use At-Home and Point-of-Care Asymptomatic Screening Tests

At-home and point-of-care (POC) serial testing for purposes of screening the asymptomatic is, arguably, the most promising, long-term market for new SARS-CoV-2 diagnostics. On March 16, 2021, the U.S. Food and Drug Administration (FDA) issued new guidance to help developers of these tests bring their products to market faster. Here is a rundown of the new “Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing” (Template) and what it portends for the laboratory test development business. The Diagnostic Challenge Notwithstanding the slight uptick in early March, COVID-19 case, hospitalization and death rates across the U.S. are falling and, knock on wood, will continue to do so in the coming months. Regrettably, though, COVID-19 is not going away; nor is the need for SARS-CoV-2 testing. However, what will change are testing demands and utilization patterns. As the virus retreats, the emphasis is bound to shift from testing the symptomatic for the purposes of providing medical treatment to testing the asymptomatic for screening. Of course, these products will have to get past the FDA goalie and secure Emergency Use Authorization (EUA) to reach the market. And therein lies the problem. Previously, all of the templates that the agency had created to help developers get EUA were for products designed to test patients with COVID-19 symptoms, recent exposure and other risk factors. Although the agency had signaled its interest in authorizing such tests, it had not developed a template for tests to be performed on asymptomatic individuals on a serial basis as part of a screening program. And without guidance, many developers have been understandably reluctant to invest in serial tests. The Template may allay these fears and drive development of SARS-CoV-2 serial tests for use in screening. The SARS-CoV-2 Screening Test Template The Template is more than just guidance and advice. It opens a streamlined and expedited path for EUA of serial tests, specifically POC or at-home tests with demonstrated strong performance in symptomatic persons. For the first time, the FDA has indicated that it will grant EUA for such tests for over-the-counter (OTC) use without first requiring them to be validated in asymptomatic individuals. In a statement, the FDA expressed its belief “that evidence of a test’s strong performance in symptomatic patients combined with serial testing can mitigate the risk of false results when testing asymptomatic individuals.” The Template’s target audience is developers of molecular and antigen tests for serial use by asymptomatic individuals at home as part of a testing program, such as by health care workers under an employer screening program designed to prevent workplace infection. The FDA suggests that individuals in such programs be tested twice over two to three days with a minimum of 24 hours and maximum of 36 hours between tests. However, developers can still seek clearance for less frequent testing regimens, such as twice a week. Exception: Only “higher sensitivity molecular tests” will be considered for tests of once or week or wider frequencies. The Template explains what developers must do to demonstrate the effectiveness of a test’s performance in symptomatic individuals to qualify for expedited EUA. Specifically, developers may generate validation data by testing symptomatic individuals serially according to the guidelines. According to the Template, the FDA will consider authorizing serial tests for OTC use at-home and POC tests if they have a positive percent agreement of 80 percent or greater (compared to PCR) with 70 percent at the lower bound of the two-sided 95 percent confidence interval. Serial tests with sensitivity in symptomatic individuals below 80 percent could still receive EUA; but the Template says that “clinical evaluation in an asymptomatic population would generally be expected prior to authorization of a screening claim, including for OTC use” for tests below the 80 percent mark. Tests authorized for screening based on symptomatic data will also have to be validated in asymptomatic individuals within a certain timeframe. The FDA also says that it may revise or revoke the EUA of tests that are not validated and that do not show adequate performance in asymptomatic individuals. Takeaway Generating data to demonstrate the performance on asymptomatic individuals has been a major bottleneck to development of serial SARS-CoV-2 tests designed for asymptomatic screening. But under the Template, developers may no longer need that data to secure EUA for their products. Companies in a strong position to benefit from this new regime include Quidel, which is currently developing an OTC version of its QuickVue SARS test, as well as those who have products already cleared for at-home use (see the box below). To date, only three companies have gotten EUA for OTC COVID-19 diagnostic products:

• Ellume for its all-in-one Ellume COVID-19 Home Test*; and
• Cue Health for its Cue COVID-19 Test*; and
• LabCorp for the Pixel by LabCorp COVID-19 Test Home Collection Kit.

COVID-19 Products with EUA Clearance for At-Home Testing

• TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific)
• BinaxNow COVID-19 Ag Card (Abbott Laboratories)
• EmpowerDX At-Home COVID-19 PCR Test Kit (Clinical Enterprise, Inc.)