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More Serological Tests Removed Since Initial Listings: Changing FDA Regulations Complicate Selecting and Using SARS-CoV-2 Serology Assays


The FDA’s unusual process by which SARS-CoV-2 serology tests have been permitted for use in the US has complicated the process of selecting which serology assay clinical laboratories should be using.

Under federal policy issued March 16, 2020, the FDA granted what it called “regulatory flexibility for developers offering such tests without FDA review and without an emergency use authorization.” (Italics by COVID-19 STAT Intelligence Briefings Service)

Under these modified rules of March 16, COVID-19 serology test manufacturers were simply required to notify the agency that they had validated their tests and provide disclaimers about the limitations of the tests. At the time, the FDA added also that it “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.

“The reasoning the 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. “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,” said Klein in an interview for The Dark Report

Roger D. Klein, MD, JD, is 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.

With about 200 serology tests pushed into the market without federal oversight, many tests were of dubious quality, said Roger D. Klein, MD, JD, in an interview for The Dark Report. Most were the product of “marginal foreign manufacturers.” The number of tests removed from the market since keeps ticking up. (Photo used with permission.)

Many Early Antibody Tests Were from “Marginal Foreign Manufacturers” 

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 the 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. 

“The reason the FDA reacted when it did was probably for several reasons,” Klein 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.”

Since this interview with Klein, the 10-business-day timeframe that required action from serological test manufacturers has expired. Many manufacturers chose not to apply for an FDA EUA, or they withdrew their notification.

Rejected or Withdrawn SARS-CoV-2 Serological Tests Have Ticked Up

On May 21, 2020, the FDA issued a list of SARS-CoV-2 serology tests for which commercial manufacturers had previously notified the FDA of their validations and intent to distribute, but had not submitted or been issued an EUA. The FDA also lists manufacturers that have voluntarily withdrawn their notification. The list has recently grown to 41. The new list provided by the FDA clearly states “Removed – Should Not Be Distributed” under the status section for each test on the list. An asterisk is placed beside tests that have been voluntarily withdrawn. The FDA has reported that this list will be kept up to date for any future developments.

“FDA expects that the tests on this list will not be distributed unless and until an EUA is issued for the test, and FDA may take additional actions as appropriate,” the FDA states on its website.

Meanwhile, respective of the EUA-authorized serological tests that remain on the market, the FDA clarifies its website listing information as “an incomplete representation of the performance.” Additionally, “FDA also is providing a calculator that will allow users to see the estimated performance of a single test or two independent tests based on their performance characteristics and the estimated prevalence of SARS-CoV-2 antibodies in the target population.”

Clinical laboratories should be aware of the status of both available and removed serology assays. Avoiding tests that are no longer permitted for use or distribution by the FDA, as well as carefully studying how available tests have performed, will help clinical laboratories and pathology groups to avoid misguided capital expenses and the expenses of sourcing unneeded reagents, while also reducing the potential risk of litigation due to inaccurate tests.

To assist in the assurance of quality and accuracy of COVID-19 serology tests, COVID-19 STAT and Dark Daily hosted a webinar, June 11, in collaboration with Westgard QC. The information presented may be accessed here.

Caleb Williams

—By Caleb Williams, Editor, COVID-19 STAT

Related Resources:

Expert Offers Comments on FDA and Revised Serology Test Rules

EUA Authorized Serology Test Performance

EUA Template for SARS-CoV-2 Serology Tests

List of SARS-CoV-2 Serology Tests Removed from FDA Notification List