After allowing unreviewed antibody tests to pervade the U.S. market for weeks, the FDA is closing its open-door policy for coronavirus blood serology tests—bringing their oversight more in line with the molecular diagnostics used to confirm active cases of COVID-19.
Since mid-March, the FDA has let manufacturers distribute unauthorized antibody tests, provided they validate the tests themselves and do not advertise them as a standalone method of diagnosing a patient. Instead, they could be used to track the spread of the virus through the population, by detecting signs of an immune response to a previous infection.
However, both the demand and reliance on these blood tests have grown, as more governments have incorporated widespread serology testing—and the potential of antibodies to bring immunity to the coronavirus—into strategies for removing lockdowns and reopening their economies, by allowing people with some level of protection to return to work.
These tests could also be used to identify people who have recovered from the disease as potential donors of convalescent plasma, which could be used to treat others.
In the U.S., several dozen test manufacturers, many from China or overseas, had notified the FDA of their intentions to sell about 170 different antibody diagnostic products in the country without seeking an agency authorization. Several more U.S. laboratories have developed their own internal blood tests.
However, the accuracy of these tests have not been established. In one example, the Spanish government was forced to return shipments of antibody tests imported from a Chinese manufacturer, after finding their performance was less than advertised.
And late last month, members of Congress called on the FDA to heighten its oversight and crackdown on COVID-19 antibody diagnostics, as part of an investigation into the government’s testing response. Still, the science is still out on whether a positive antibody test result, even an accurate one, would be a reliable gauge of immunity against the disease.
The agency’s experiment in regulatory flexibility also led to confusion among several companies, with some mistakenly claiming their tests were authorized or approved by the FDA under the policy. At the same time, truly fake tests have been sold over the Internet, promising a way for people to test for COVID-19 at home.
In an FDA blog post outlining the new policy, the agency’s device center director, Jeff Shuren, and Deputy Commissioner Anand Shah said “flexibility never meant we would allow fraud.”
“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” they wrote.
In addition, “the FDA has become aware that a concerning number of commercial serology tests are being promoted inappropriately, including for diagnostic use, or are performing poorly based on an independent evaluation by the NIH.”
Shuren and Shah said the agency has been working to intercept illegitimate tests at international mail facilities, stop companies’ false marketing, and will provide updated notices to states and healthcare providers.
Under the new policy going forward, the FDA will still allow companies to distribute and market self-validated antibody tests for a short period of time as they prepare and file their review requests—similar to the guidance given to molecular test manufacturers.
Antibody test developers will be expected to submit official requests for an Emergency Use Authorization—along with their validation results—to the FDA within 10 days. The agency also said it is recommending specific thresholds for the tests’ accuracy, specificity and sensitivity.
In addition, the makers of the aforementioned 170 antibody tests currently being marketed in the U.S. will be required to submit an EUA request within 10 days, or the agency will publicly note that these tests are unreviewed and unauthorized and may take additional actions, such as issuing injunctions or warning letters.
“To date, 12 antibody tests have been authorized under an individual EUA, most within just the past few days, and over 200 antibody tests are currently the subject of a pre-EUA or EUA review,” said Shuren and Shah, referring to pre-submissions where developers have sought advice or shared data with the agency.
The FDA has also been working with the NIH and CDC to independently validate antibody tests, submitted voluntarily by their manufacturers. Thirteen have been evaluated so far, according to the FDA, with the data still under review. The agency recently issued an umbrella EUA for antibody tests that complete the NIH validation process.