FDA leaders recount flaws in 2020's open-door policy for COVID-19 antibody tests

To get tests into the hands of healthcare providers as fast as possible during the early throes of the COVID-19 pandemic, the FDA opened its gates to commercial diagnostic developers nearly one year ago, letting them enter the market without first obtaining federal permission—and, in the case of antibody tests, allowed them to be sold and shipped unreviewed as long as they carried certain caveats, while the agency instead focused on evaluating a deluge of new molecular diagnostics for active coronavirus infections.

Now, the leaders of the FDA’s medical device and testing divisions say that move was a mistake.

Over last March and April, companies began to flood the market with antibody blood tests—including some mislabeled as carrying the FDA’s official seal of approval—and still more offered unverified claims of accuracy, while independent researchers found high rates of false results.

Still, governments worldwide sought to procure millions of tests, pitching them as a prerequisite for lifting lockdowns and reopening economies, though at the time it was a scientific unknown which types of antibodies and what amounts would be necessary for a positive test result to be equated with any kind of protection from the virus.

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“We planned to revisit this policy after authorizing several serology tests. In hindsight, however, we realized that the policy outlined in our March 16 guidance was flawed,” wrote the FDA’s device center director, Jeff Shuren, M.D., with the agency’s in vitro diagnostics chief, Timothy Stenzel, M.D., Ph.D., in an editorial published in The New England Journal of Medicine.

Within two weeks, 37 commercial manufacturers had alerted the agency of their plans to move forward with selling antibody tests. By the end of the next month, that number had grown to 164.

“This series of events differed from our experience with commercially manufactured diagnostic tests,” Shuren and Stenzel said, adding that serological tests had previously played limited roles in past viral outbreaks and were rarely used in immediate clinical care.

“In that case, very few tests were offered under notification; manufacturers generally marketed their own tests, rather than products made by other, typically non-U.S. manufacturers, as occurred with some serology tests; and false claims and data falsification were much less common,” they said.

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Though the FDA would roll back this policy in early May and increase its oversight, it would later name more than two dozen products to be removed from the market entirely—and ultimately nix listings for 225 tests from the agency’s website, issue at least 15 warning letters and place import alerts on 88 companies to allow their shipments to be seized at the border over the rest of the year.

The agency also launched a concerted effort with researchers at the National Institutes of Health, the National Cancer Institute, the Biomedical Advanced Research Development Authority and the Centers for Disease Control and Prevention to appraise the accuracy of antibody tests themselves—the first time the federal government evaluated a diagnostic product on its own to help FDA reviewers make their decisions.

Since the beginning of the pandemic, the FDA has officially authorized an average of nearly one test per day across all different diagnostic types and settings ranging from the laboratory to the point of care to in the home.

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When it comes to lessons learned, Shuren and Stenzel said the experience “underscores the importance of authorizing medical products independently, on the basis of sound science, and not permitting market entry of tests without authorization.”

The two FDA officials also called for the federal government to prepare a public-private research plan to coordinate the study of future epidemics and measures of immunity—and to build the capacity to evaluate the performance of tests before outbreaks occur.

“Our collaboration with the NCI showed us the value of this approach,” they said. “Combined with FDA authorization, this strategy could permit rapid independent assessment of molecular diagnostic, antigen, and serology test accuracy and minimize the need for developers to find patient specimens or other clinical samples to validate their tests, thereby expediting the availability of accurate tests.”

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They also called for national and international systems for sharing pandemic research data and information as it evolves to help avoid misuse or over-reliance on certain types of diagnostic tests.

“Knowing what we know now, we would not have permitted serology tests to be marketed without FDA review and authorization, even within the limits we initially imposed,” Shuren and Stenzel said. “Although other factors may have driven unauthorized products to flood the marketplace, our March 16 policy allowed it to happen.”