Serology testing capable of distinguishing whether SARS-CoV-2 antibodies in a person’s systems are due to a current or previous COVID-19 infection could play a pivotal role in the re-opening process and post-pandemic world. As with any new diagnostic tests, the FDA represents the gateway serological SARS-CoV-2 antibody tests must pass to reach the market. So, it’s not surprising that the agency’s policy—or, as some describe it, lack thereof—has become the focal point of attention now that the COVID-19 case curve has flattened out and society prepares to reemerge from lockdown.
The FDA’s Serology Testing Pathways
After initially resisting the idea, the agency has taken a test-now/regulate-later approach to COVID-19 diagnostic testing, permitting high-complexity CLIA and commercial labs to provide their own tests immediately upon validation without waiting from, and in some cases, even seeking Emergency Use Authorization (EUA) from the FDA. Among the four new pathways or “Policies,” two can be used by test makers to launch SARS-CoV-2 antibody serology tests:
Manna from Heaven or Junk Science?
- Policy C, which allows for the launch of tests for use at the point of care upon validation without an EUA, provided that the test maker notifies the FDA immediately and submits an EUA application within 15 business days; and
- Policy D, an even less rigorous pathway which allows for launching of validated tests without having to secure EUA at all.
The positive aspect of the FDA policy is that new COVID-19 serology tests have become available in record time. The downside is that the tests are, to put it generously, unproven. Thus, among the 148 serology tests being provided, only seven have actually gotten EUA clearance, including assays from Dia Sorin, Chembio, Cellex and Abbott. The other 141 have passed through the Policy D pathway.
In addition to false claims by Policy D serology test makers about the capabilities of their products and suggesting that they have FDA approval, there’s major concern about their lack of accuracy and reliability. Serology tests are especially vulnerable to specificity issues that can produce false positive results, leading people who are still susceptible to COVID-19 into falsely believing they’re immune.
The FDA has come under fire for relying too heavily on serology testing and allowing “junk tests” to reach the market. Test makers are taking advantage of Policy D to market fraudulent tests, according to an April 24 House Oversight and Reform Subcommittee preliminary investigation report.
Meanwhile, FDA efforts to encourage test makers to get clearance through Policy C and voluntarily submit their tests for independent validation are being ignored.
The congressional report cites the FDA for failing to “put forth standards and guidelines for serological antibody tests, departing from practices governing molecular tests.” Compounding the problem, the agency has failed to take any enforcement action against any company for making false claims about its Policy D serology SARS-CoV-2 antibody test products.
The FDA is doing everything it can to promote rapid development of serology testing that scientists and policy makers can rely on to evaluate the current scope of the COVID-19 pandemic and identify individuals who can safely return to work. But because of the low prevalence of COVID-19 among the general population, extremely high accuracy of test results is of critical importance. Regrettably, lack of specificity makes SARS-CoV-2 antibody testing prone to false positives, an accuracy flaw that carries potentially dangerous consequences. So, the current FDA policy of clearing such tests without the usual regulatory scrutiny is a roll of the dice with monstrously high stakes.
FDA Creates New Pathway for SARS-CoV-2 Serology Tests
On April 29, as we were going to press, the FDA announced that it has created a new “umbrella” pathway for EUA clearance of serology tests requiring test makers to submit tests for evaluation by an interagency testing group at the National Cancer Institute. Tests under review will be run against a panel of samples confirmed positive for anti-SARS CoV-2 IgM and IgG antibodies.
Tests will also be run against confirmed antibody negative samples or pre-COVID-19 samples, with 10 of these 80 negative samples being HIV positive. To receive clearance, tests reporting on both IgM and IgG must perform with overall sensitivity of 90 percent and specificity of 95 percent. Tests reporting the immunoglobulins separately must have sensitivity for IgM of at least 70 percent and 90 percent for IgG. Tests must also show no cross-reactivity with HIV.