CEO SUMMARY: After introducing some 200 serological assays onto the market in March and April with little or no review, as of this writing the FDA website lists only 77 serology tests. Of that number, 11 assays have been evaluated independently and eight of those 11 have been pulled from the market. Also, the FDA says 45 tests should no longer be distributed, and among those tests, 21 had been granted emergency use authorizations and 11 were removed voluntarily by the manufacturers.
NEW EVIDENCE PRODUCED BY FEDERAL RESEARCHERS indicates that a substantial number of COVID-19 serological tests that currently have a Food and Drug Administration (FDA) emergency use authorization (EUA) may fail to perform to the minimum requirements established by the FDA.
This situation is a cause of great concern for pathologists and clinical laboratory administrators throughout the country because of the huge—and steadily increasing—demand for accurate and reliable COVID-19 serological tests.
Yet, the latest findings of a federal research laboratory show that 73% of the COVID-19 serology tests with an FDA EUA reviewed to date fail to meet the requirements established by the FDA!
This is extremely bad news for clinical laboratories in the United States. They rely on the FDA to issue standards and clear diagnostic instruments and tests for market that perform reliably, accurately, and produce high-quality test results for use in clinical settings.
Moreover, labs are at risk for liability, malpractice and similar other legal claims if they produce lab test results that fail to meet the standards for accuracy and clinical care. For this reason, the FDA’s careful review and clearance of a medical device or a diagnostic test is meaningful and important for clinical laboratories, the physicians who order tests, and the patients being tested.
Since June 1, the FDA has twice released sets of performance data on COVID-19 serology tests with EUAs that were generated by independent evaluations conducted by the FDA and the National Cancer Institute (NCI). Based on the assessment of each test’s performance, the FDA then assigned a marketing status to those tests.
The first data release was on June 4. The FDA announced that, of the three COVID-19 serology tests evaluated, only one could continue to be marketed.
Eleven Tests Evaluated
The next data release came on June 19. The FDA and NCI had completed evaluations on a total of 11 tests and determined that only three can continue to be marketed under the EUAs the agency granted. This meant that eight of the tests reviewed—each of which had an EUA—could no longer be marketed.
These poor results from the FDA’s own review of COVID-19 serology tests with EUAs raise major concerns. Across the nation, many labs are negotiating to purchase and validate COVID-19 serology tests that have EUAs.
The fact that of the first 11 such tests reviewed by a federal laboratory, eight tests can no longer be marketed raises a valid point: can a clinical lab be confident that when it purchases a COVID-19 serology test with an EUA for use in patient care, the test will deliver accurate and reproducible results?
In truth, the fact that the majority of COVID-19 serology tests reviewed to date by federal researchers cannot be marketed is now the latest chapter in an ongoing series of bad decisions and missteps happening at the FDA.
Experts in diagnostics and laboratory medicine have publicly criticized the FDA for certain actions it has taken in its response to the COVID-19 pandemic. At a time when state governors and the president want to unleash the full potential of clinical labs to respond to the pandemic, certain of the FDA’s directives have been counter-productive in enabling the nation’s labs to deliver the large volumes of testing required to manage the pandemic.
The FDA’s release of research lab findings that 73% of COVID-19 serology tests reviewed failed to meet requirements is the latest chapter in a story that began with the COVID-19 outbreak earlier this year. The serological test part of this story began in March.
On March 16, the FDA issued rules allowing lab test manufacturers to market serological tests for the coronavirus with little or no agency review. At the time, the agency said it was granting “regulatory flexibility for developers offering such tests without FDA review and without an emergency use authorization (EUA).”
The test manufacturers needed to notify the agency that they had validated their serological tests and provide disclaimers about the limitations of the tests. “The FDA does not review the validation or accuracy of the data for these tests unless an EUA is submitted,” said the federal agency at that time.
No Performance Analysis
The suspension of FDA review for COVID-19 serological tests was designed to both shorten the time for such tests to reach the market and increase the number such tests available for purchase and use by clinical laboratories. But listing tests without a traditional review by the federal agency created exactly the problem predicted by critics.
They foresaw that the FDA’s relaxation of rules governing COVID-19 serology tests would allow companies—many without any operating history—to list a COVID-19 assay with the FDA, supported by minimal data, then offer it in the marketplace.
After the FDA opened the floodgates to test developers, more than 200 serological tests for the coronavirus were listed on the FDA’s registry and poured into the market in March and April. It meant clinical laboratories were on their own to determine which of these tests would be accurate and high quality and which would not.
Strong evidence that FDA officials realized the folly of issuing the relaxed rules for allowing COVID-19 serology tests into the market with review came just seven weeks later. On May 4, the agency reversed course and issued new guidance on serology testing. (See TDR, “FDA Replaces March 16 Serology COVID-19 Rules,” May 11, 2020.)
Tighter Rules for COVID Tests
The FDA’s new guidance required test manufacturers to either register their coronavirus antibody assays with the agency and obtain EUAs to market the tests or to withdraw their tests. Since then, no more than 77 such COVID-19 serology tests are listed on the FDA’s site. This number fluctuates almost daily as tests are added and deleted.
Of those 77 tests, the FDA said 11 have been evaluated independently, 21 have been granted emergency use authorizations, and 45 should no longer be distributed.
About those 45 tests, however, the agency provides little detail on why they were pulled except to say that the manufacturers of 11 of the 45 tests removed those assays voluntarily.
Most significantly, the FDA, the NCI, and other federal health agencies have collaborated to conduct independent evaluations of 11 of the serological assays for the coronavirus. These evaluations are significant because eight of those 11 tests have been pulled from the market as a result of poor performance, according to the FDA and NCI, a division of the National Institutes of Health.
To the credit of the FDA, it is proceeding with an assessment of COVID-19 serology tests that are listed on its site. This work is being done at the Frederick National Laboratory for Cancer Research (FNLCR), a federal research and development center affiliated with the NCI.
Yet, it is a troubling fact that the first results of these evaluations show that eight of the 11 COVID-19 serology assays evaluated by FNLCR are to be removed from the market. These findings put a cloud over many of the COVID-19 serology tests still listed on the FDA’s site.
One expert on diagnostic testing told The Dark Report that the FDA and FNLCR testing program appeared to focus on the “poorly-performing tests coming from China and from other parts of Asia and being offered for sale in the United States.” He further noted that “the findings are unsurprising and should not be extrapolated to tests from known and reputable manufacturers.”
Test Performance Questions
There is another reason why the uncertainties about the performance of certain COVID-19 serology tests listed on the FDA’s website is a problem. It is already obvious in the marketplace that the major IVD manufacturers are devoting most of their available supplies of reagents andtest kits to their larger lab customers.
Meanwhile, community hospital labs, independent labs, and physician’s office labs that are CLIA-certified as complex labs are not able to buy sufficient quantities of COVID-19 tests from the major vendors to meet even minimum needs.
Therefore, these are the labs most likely to go to the FDA’s website and purchase COVID-19 serology tests listed there made by lesser-known companies. Labs relying on the FDA’s serology test listings should proceed cautiously.
FDA Says 45 COVID-19 Serological Tests Should No Longer Be Distributed for Clinical Use
ON THE WEBSITE OF THE FEDERAL FOOD AND DRUG ADMINISTRATION, there does not appear to be a list of the 200 or so serology tests for the SARS-CoV-2 coronavirus that were approved for marketing in March.
And, there does not appear to be a full explanation for why the FDA accounts for the disposition of only 77 serology tests for the antibodies. There is, however, a list of 45 tests that the FDA says should no longer be distributed for COVID-19.
In a statement, a spokesman for the FDA said, “Antibody tests on this new removal list include those voluntarily withdrawn from the notification list by the test’s commercial manufacturer and those for which there is not a pending emergency use authorization (EUA) request or issued EUA. FDA expects that the tests on the removal list will not be marketed or distributed.”
Of the 45 tests on the “not to be marketed or distributed” list, there are 11 that the manufacturers have removed voluntarily.
• Artron BioResearch/Artron Labs: COVID-19 IgM/IgG Antibody Test
• BioMedomics: COVID-19 IgM-IgG Rapid Test
• Diazyme Laboratories: Diazyme SARS-CoV-2 Antibody Rapid Test
• Genlantis Diagnostics: CovidQuik Coronavirus (COVID-19) IgM/IgG Antibody Test
• Hangzhou Testsea Biotechnology: One Step SARS-CoV-2(COVID-19) IgG/IgM Test
• Hunan RunKun Pharmaceutical: SARS-CoV-2 lgM/lgG Test Kit (Colloidal Gold)
• IMMY: clarus SARS-CoV-2 Total Antibody EIA
• Phamatech: COVID-19 IgG/IgM Rapid Test
• Saladax Biomedical: COVID-19 IgG/IgM Rapid Antibody Test
• Shenzen Landwind Medical: COVID-19 IgG/IgM Rapid Test
• Zhuhai Encode Medical Engineering: Novel Coronavirus (COVID-19) IgG/IgM Rapid Test
Three Serology Tests Can Remain on Market
IN ITS JUNE 19 ANNOUNCEMENT ABOUT THE TEST REVIEW, the FDA stated that three COVID-19 serology assays can remain on the market and that each had sensitivity and specificity levels of 90% or higher. Those three tests were:
• Euroimmun: SARS-CoV-2 ELISA (IgG)
• Hangzhou Biotest Biotech: COVID-19 IgG/IgM Rapid Test Cassette
• Healgen: COVID-19 IgG/IgM Rapid Test Cassette.
Eight tests the FDA said should not be distributed for sale all had sensitivity and specificity levels well below that of the three tests that were authorized for sale.
Among the eight that should not be distributed, the FDA revoked the EUA for Chembio Diagnostics’ DPP COVID-19 IgM/IgG System. About this test the FDA said: “On June 16, FDA determined that the statutory criteria for issuing an EUA … are no longer met. Specifically, FDA determined that it is not reasonable to believe the product may be effective in detecting antibodies against SARSCoV-2 or that the known and potential benefits of the device when used for this purpose outweigh its known and potential risks.
FDA also concluded that based on the risks to public health from false test results, revocation is appropriate to protect the public health or safety.”
The manufacturers of three other tests withdrew their assays voluntarily. When the FDA shows the marketing status as “should not be distributed—voluntarily withdrawn,” the manufacturer has stopped distribution and asked the FDA to remove the test from among those offered for sale.
When the marketing status is “should not be distributed—removed,” either an EUA request was not submitted on time or the FDA determined not to issue an EUA for the test, the agency noted.