FDA Likely Regretting ‘Unapproved’ Antibody Test Policy

FDA is likely regretting its policy introduced last month that allowed dozens of Covid-10 serology (antibody) tests to come onto the market without normal vetting or review under the agency’s emergency use authorization pathway. Now that the floodgate is open for test developers, 117 “unauthorized” antibody tests are on the market, and almost daily FDA is taking some action due to concerns about their accuracy. The agency recently updated its Web site to better clarify which tests have been authorized by FDA and which have not.

Because of the initial slow rollout and criticism involving Covid-19 testing, FDA said it wanted more flexibility for serological tests in an effort to give laboratories and health care providers early access to the tests with the understanding that the FDA had not reviewed or authorized (“approved”) them, at least not initially, and that the tests should not be used for diagnosing or excluding active infections. Last month’s FDA policy change tried to explain that the agency would not object when developers of serological tests market or use their tests without prior FDA review where: (1) the tests are validated by the developer to determine that they are accurate and reliable, (2) notification of the developer’s validation is provided to FDA, and (3) the tests are labeled appropriately, including that they are not to be used as a sole basis for diagnosis.

In a 3/18 post, FDA commissioner Stephen Hahn said that some test developers have misused the serology test kit notification list to falsely claim their serological tests are FDA approved or authorized. “Others have falsely claimed that their tests can diagnose Covid-19,” he said. “When we become aware of these issues, we have and will continue to take appropriate action .... such as issuing Warning Letters requesting that companies stop their unlawful promotion and detaining and refusing fraudulent test kits at the border.”

Hahn said the agency is continuing to allow interested serology test developers to request FDA authorization through the EUA process, and so far four EUAs for serological tests have been granted. He said FDA is also collaborating with the National Institutes of Health’s National Cancer Institute, National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention to “establish a capability at NIH to evaluate serological tests for developers. This effort includes tests already available for use, as well as tests not yet on the market where additional validation data is needed to support an EUA. Performance assessments for serological tests will begin soon, and we expect to start seeing results shortly thereafter. We will review NIH’s results expeditiously, and performance results from NIH’s assessment may complement and inform the determination of whether FDA issues an EUA for a particular test.”

Additionally, Hahn said that all clinical tests should be validated prior to use. “We have provided regulatory flexibility regarding the independent check by FDA for antibody tests that are limited in their clinical applications, but still expect all developers to validate their tests prior to offering them for limited clinical uses,” he said. To reduce the number of false positive results, serological tests must be “well-designed to specifically identify antibodies” against Covid-19 and must not “cross-react,” or provide positive results when encountering antibodies against other respiratory viruses.

Meanwhile, FDA 4/21 issued a “Dear Healthcare Provider” letter telling them to be aware of the limitations of serological tests and the risks to patients and the community if the test results are used as the sole basis to diagnose Covid-19. It said the agency is not aware of an antibody test that has been validated for diagnosing Covid-19 infections. “While the FDA remains open to receiving submissions for these tests for such uses, based on the underlying scientific principles of antibody tests, the FDA does not expect that an antibody test can be shown to definitively diagnose or exclude SARS-CoV-2 infection,” the letter said.