Expert Offers Comments on FDA and Revised Serology Test Rules

Tougher rules issued on May 4 show FDA’s concern about faulty or fraudulent COVID-19 serological tests

CLINICAL LABORATORY DIRECTORS are asking what caused the federal Food and Drug Administration (FDA) to issue a highly questionable policy in March to allow serological tests for SARS-CoV-2 and then change that policy seven weeks later.

Under a policy the agency issued March 16, the FDA granted what it called “regulatory flexibility for developers offering such tests without FDA review and without an emergency use authorization.” (Italics by TDR.)

No Agency Review of Tests

Under the modified rules of March 16, test manufacturers were simply required to notify the agency that they had validated their serological tests and provide disclaimers about the limitations of the tests. The agency added, however, that “The FDA does not review the validation, or accuracy, of the data for these tests unless an EUA is submitted.”

In the ensuing weeks, the market was flooded by more than 200 COVID-19 antibody tests. Some of these tests were faulty and others were fraudulent, according to published reports.

Many lab professionals questioned why a federal agency known for its often-rigorous review of lab tests and other medical devices could be so lax about serology tests in the midst of a pandemic.

“The reasoning FDA gave on March 16 for allowing COVID-19 serological tests without review was the simplistic notion that these tests are less complex than molecular tests,” commented Roger D. Klein, MD, JD, a former adviser to the FDA and a faculty fellow at the Center for Law, Science and Innovation at the Sandra Day O’Connor School of Law at Arizona State University.

“Further, FDA stated that because serologic tests have limited usefulness for diagnosis, the agency assumed the tests would be used primarily for epidemiologic purposes,” added Klein. “This explanation isn’t wholly satisfactory, however, because serology testing performed for epidemiologic purposes doesn’t require FDA authorization,” continued Klein. “In addition, the potential of using serology tests as a surrogate for immunity to COVID-19—which could permit some individuals to safely return to work—has been a topic of discussion for some time.

Surrogate for Immunity

“This additional potential use—the serology test result as a surrogate for COVID-19 immunity—should have been apparent to the agency,” he commented. “I suspect FDA’s March 16 policy was in part a reaction to the FDA’s role in delaying the introduction of diagnostic testing early in the epidemic, for which it has been widely criticized,” Klein added. (See “Regulators Acted Slowly as Labs Developed Tests for Coronavirus,” TDR, March 30, 2020.)

Next, Klein addressed why the agency changed its policy for review and clearance of COVID-19 serological tests on May 4 to require test manufacturers to withdraw their serological assays or seek emergency use authorizations for these products.

“It’s likely that FDA did not anticipate a flood of serology test products, many of which are from China and other Asian countries and some of which are of questionable quality,” Klein explained. “It appears that significant numbers of COVID-19 serology tests were introduced from marginal foreign manufacturers.” But why did the FDA take so long to address this situation? “The reason the FDA reacted when it did was probably for several reasons,” he noted. “It’s likely the agency recognized some of these tests were of dubious quality, and in part it was a response to news reports in major media outlets that raised questions about many of the 200 or more tests offered without review. As well, some of those news reports cited a study that appeared to highlight some of the poor or uncertain performance among some of the tests.

Use in Non-CLIA Lab Settings

“Plus, FDA intended for serology tests to be performed in CLIA-certified laboratories, but some companies used them outside CLIA settings,” Klein added. “There were also cases where certain manufacturers falsely claimed that the FDA authorized their COVID-19 serology tests for use.”

The FDA’s new policy announced May 4, could generate a significant amount of work for the agency, he said. “It could raise new concerns about how long reviews will take and whether there will be significant delays in getting tests on the market.”

As of May 8, the FDA had approved emergency use authorization for 12 of the original 200 or more serological assays and listed 116 of those tests as “Not FDA Authorized.” It was not clear if the manufacturers had withdrawn the remaining assays.

Klein noted, however, that all of the test manufacturers were supposed to have validated their tests prior to offering them. Therefore, they should have already done that work before the FDA does its EUA review, which should help shorten the time to authorization, he added.

Properly-Validated Tests

“Also, the number of submissions may be far less than the numbers of tests currently offered,” Klein said. “Most of the reputable manufacturers that properly validated their serological tests will submit theirdata to FDA. However, those companies that did not fulfill these basic requirements may not respond at all.

“I expect the legitimate manufacturers that validated their serological tests and provided validation summaries and performance specifications to customers will submit their data to the FDA under the new rules,” Klein commented. “If they do, then it seems likely suchtests will continue to be legally sold after submission and before final review, unless FDA sees red flags or other potential risks in specific tests,” he added. “For these companies, the review times need not be long because so much of the necessary work has been completed.

“Some manufacturers—and perhaps even a large percentage of them—will not submit data to the FDA,” Klein said. “And, I suspect that some sellers in this group may even continue to sell their products here illegally.

“It should also be noted,” he continued, “that FDA has already granted EUAs to about a dozen or so tests from reputable manufacturers with acceptable or even excellent performance. That means clinical laboratories currently have multiple choices when deciding which serological test for COVID-19 they want to use.”

Pathologists and clinical laboratory managers can expect to see continuing news headlines about serological testing because of the need to test large numbers of individuals to determine if they have been infected with COVID-19. TDR

Contact Roger Klein, MD, JD, at



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