False Positive Recalls Casts Doubt on Rapid COVID Screening Tests at the Worst Possible Time

Late last year, the US Food and Drug Administration (FDA) began issuing emergency use authorization (EUA) for a new breed of COVID-19 tests designed not so much to diagnose but screen for the virus on a rapid and scalable basis at the point of care. But in recent months, accuracy problems have come to light that have resulted in a series of recalls of these tests. The most recent recall came on October 15 when the FDA issued a Class 1 recall for a pair of high throughput tests from Abbott Laboratories.

The Rapid COVID-19 Testing Linchpin

The stakes are incredibly high. As the pandemic has drawn on, the focus of diagnostic testing has shifted to rapid point-of-care and over-the-counter, at-home products allowing for screening the asymptomatic population. Many of these tests are sold over the counter by retail giants like Amazon, CVS, Walmart and Target. Last month, the Biden Administration unveiled a plan calling for the federal government to spend $2 billion to make these tests more widely available to the public.

But while they offer scalability and speed, questions remain about whether rapid at-home and high throughput COVID-19 screening tests are accurate enough to provide a reliable solution. And the recent recalls threaten to undermine public faith in these tests just at a time when they are being counted on the most.

The Ellume Recall

On December 15, 2020, the Ellume COVID-19 Home Test became the first fully at-home SARS-CoV-2 testing kit to receive EUA for over-the-counter sale. In studies, the 20-minute antigen test registered an overall sensitivity of 96 percent and specificity of 100 percent. In February, the Australian test maker cut a $231.8 million deal with the Departments of Defense and Health and Human Services to establish a US production facility and crank out 8.5 million of the tests for distribution across the country.

On October 5, Ellume recalled 200,000 of the test kits shipped to US retailers from April through August due to concerns that they were reporting a higher than expected rate of false positive results. The recalled lots also included 227,000 kits that had already been used. Ellume said it plans to email customers who used the kit over the previous two weeks that if they tested positive, they should immediately schedule another test to confirm the results. The FDA issued a statement of its own recommending that those individuals immediately get a molecular test. The manufacturing issue causing the false positives problems apparently did not apply to the negative test results.

The Abbott Recall

Abbott Laboratories has also been among the leaders in developing tests to meet the demand for high throughput COVID-19 test products. In addition to its BinaxNOW rapid, point-of-care test, Abbott’s COVID-19 products suite includes tests run on its Alinity system, including the Alinity m SARS-CoV-2 AMP Kit, a real-time reverse transcription (RT) polymerase chain reaction (PCR) kit for qualitative detection of nucleic acid from the virus, which originally received EUA in May 2020 and has since been granted multiple revisions, including for use on asymptomatic screening and in pooled samples. In December, Abbott also received EUA for the Alinity m Resp-4-Plex AMP Kit, a multiplex respiratory test which detects SARS-CoV-2, influenza A and B, and respiratory syncytial virus.

But problems with the Alinity products have recently begun to surface. In early September, one month before the Ellume recall, Abbott notified its laboratory and other healthcare provider customers that it had detected an issue with the software used by special laboratory processing equipment to prepare swab samples and mix the chemicals for testing with the assays. The problem was that too much liquid might have been getting added to samples under certain mixing parameters, resulting in overflow into the neighboring process tray. False positives may occur when a positive sample overflows into a nearby negative one.

Upon receiving notification of the problem from Abbott, the FDA posted an alert on its website warning testing laboratories, providers and patients of the potential for false positive tests from the Alinity kits. In October, the agency upped the ante by issuing a Class 1 recall for the products.

According to the FDA recall notice, 187 software installations are undergoing corrections. Altogether, those programs are responsible for analyzing the results of more than 10 million already distributed tests: more than 9.9 million Alinity m SARS-CoV-2 tests and just over 48,000 of the Resp-4-Plex assays.

The Class 1 label indicates that the agency considers the issue serious, and involves a high risk of causing serious adverse events or death. Some potential risks of false positives include unnecessary treatments or isolation, delayed diagnosis of the actual cause of a test-taker’s illness and the continued spread of the virus if people with seemingly positive results are quarantined together, the agency notes.

Even so, the FDA is not actually recalling the tests; for now at least, it is just warning customers to be wary of the results. Like Abbott’s previous note did, FDA has advised laboratories and providers to treat all positive results from the two affected assays as “presumptive.”

The FDA recommends retesting positive patient specimens with an alternate authorized test and notifying patients who have receive positive results from the kits since June that they may have had false positive test results and that since they might not have actually had COVID-19, they may not be carrying antibodies against the virus.

Meanwhile, the agency said it is working with Abbott to resolve the issues. The update for the SARS-CoV-2 test is nearly complete, while the update for the 4-plex test is expected to be finished in the next few weeks.

Takeaway

The Ellume and Abbott recalls are not the first affecting a COVID-19 test that has received EUA clearance. is hardly the first FDA recall of COVID-19 test products. In July, the agency issued a Class I recall of one of the first COVID-19 tests to receive EUA, the Quidel Lyra PCR assay for COVID-19. However, the issue with the Lyra test was not false positives but false negatives. More significantly, the most recent recalls target the rapid, high throughput test products that have become integral to widespread screening necessary to keep society open while the virus remains unconquered.

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This article originally appeared in G2 Intelligence, Diagnostic Testing & Emerging Technologies, November 2021.