“Stop using the Innova SARS-CoV-2 Antigen Rapid Qualitative Test.” That was the stark warning to the public from the US Food and Drug Administration on June 10, about an unapproved rapid lateral flow test used to diagnose COVID-19. Among a litany of concerns, the FDA said that the test posed a health risk because of its potential to deliver false results. And to underscore the message, the FDA added that users should “destroy the tests by placing them in the trash.”
The antigen test, supplied by Innova Medical Group in Pasadena, California, has not been authorized for emergency use by the FDA. The company says it had distributed the test to customers “for evaluation purposes,” and it is not widely used in the US. But the communiqué dropped like a bombshell in the UK, where Innova’s test forms the backbone of the government’s Operation Moonshot COVID-19 screening program. The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) scrambled to order and review a risk assessment of the test, which is used for routine screening of millions of asymptomatic people in the UK every week.
"Our priority is to ensure patients and the public have access to safe and effective medical devices and tests,” Graeme Tunbridge, the MHRA’s director of devices, says in a June 17 press release. He says, “We have now concluded our review of the risk assessment and are satisfied that no further action is necessary or advisable at this time.”
The Innova test uses a sample from a nasal and throat swab to detect specific proteins, called antigens, from the SARS-CoV-2 virus. The test indicates a positive result as a colored line on a cellulose strip in less than 30 min. Proponents say that such tests offer a quick way to identify people infected with SARS-CoV-2, even if they show no symptoms.
But some researchers have questioned the accuracy of the Innova test, and its use in mass screening, because it misses many of the positive cases that could be identified by slower reverse transcriptase polymerase chain reaction (RT-PCR) tests, widely regarded as the gold standard diagnostic. “This is a first-generation test that can only detect high levels of virus, it was never designed as a test for asymptomatic use,” says Jonathan J. Deeks, a biostatistician at the University of Birmingham who leads an ongoing review of the accuracy of SARS-CoV-2 tests for the UK-based charity Cochrane.
The sensitivity of the test also depends on who uses it. An assessment ordered by the UK government found that when laboratory scientists conducted the tests, it caught 79% of positive samples, but when used by members of the public, that sensitivity fell to 58%. In November, a city-wide screening program in Liverpool, England calculated that the test had an overall sensitivity of 40%. This has raised fears that a negative result from the test may give people false reassurance that they are not infectious, leading them to engage in riskier behaviors that exacerbate the spread of the virus.
The controversy has not stopped the UK government from awarding Innova more than £3 billion ($4.2 billion) in contracts to supply the tests. Since April 9, people without symptoms have been able to order free tests online, while schools supply students with packs of the tests. All are advised to take the tests twice weekly, and report their results to the country’s National Health Service.
This is only possible because the MHRA issued an exceptional use authorization in December 2020 allowing the tests to be self-administered at home by asymptomatic people. However, that approval came with stringent conditions. For example, the agency said it did not support using negative results from the test as a ‘passport’ to access school, workplaces, or services. In April, the regulator complained that the government’s widening use of the tests was stretching this condition of the authorization.
By early June, about 3.5 million of Innova’s lateral flow tests were being conducted per week. In total, Innova has supplied the UK with over 1 billion tests, which have returned more than 180,000 positive results since they were first introduced. Despite this, the number of recorded COVID-19 cases in the UK has been rising since social-contact restrictions were eased in mid-May.
The FDA’s warning follows an inspection of Innova’s facilities in California in March and April. In a letter to the company, the agency said that the tests had been distributed in the US without authorization, and that some tests contained “false or misleading” performance claims that appear “unsupported by any clinical data.” Innova had previously applied to the FDA for emergency use authorization (EUA) of its test, but the company now says it withdrew its application. So far, the agency has granted EUAs to four other at-home antigen tests.
Most of the company’s tests are manufactured by Xiamen Biotime Biotechnology in Xiamen, China, and the FDA’s inspection found that Innova’s quality assurance of these imported tests was inadequate. Following the FDA’s inspection, Innova initiated a recall of more than 77,000 tests in April, and the company says that it is still working to fully comply with FDA requirements. “We have enough data to support the efficacy of the test, perhaps more than any other tests of its kind in the world,” said Robert Kasprzak, Chief Operating Officer of Innova Medical Group, in an emailed statement.
The controversy exemplifies a wider problem with the authorization of diagnostic tests, according to a report from the UK’s Royal Statistical Society (RSS) published on June 9. The regulation of medical devices around the world tends to be far less rigorous than that of drugs or vaccines, and largely relies on a ‘self-certification’ process, says Sheila M. Bird, a member of the society’s working group on diagnostic tests, and formerly Programme Leader at the MRC Biostatistics Unit in Cambridge, England.
Although manufacturers often evaluate their tests in clinical settings, she adds, these diagnostics may end up being used in very different contexts once they reach the market.
“The self-certification by Innova was for use in symptomatic persons, but it is now being used for mass screening of asymptomatic persons,” Bird says. “They need to be evaluated in each specific context of use.”
Deeks, who co-chairs the RSS’s working group, notes that there are still no published studies about how well the test can detect cases in children, or when used for self-testing by asymptomatic people—both key components of the government’s testing program.
The government’s Department of Health and Social Care has maintained its confidence in the test.
“We have a robust quality assurance process in place,” it says in a statement. On June 17, the MHRA extended the exceptional use authorization for the Innova test to Aug. 28.
This story was updated on June 16, 2021 to clarify the status of Innova Medical Group's emergency use authorization application in the US. The story previously said Innova had not yet received a decision from the US Food and Drug Administration. It has withdrawn its submission.
This story was updated on June 17, 2021, to include commentary from Graeme Tunbridge of the Medicines and Healthcare Products Regulatory Agency on the government’s risk assessment and to note the extended exceptional use authorization of the test in the UK.