COVID-19 Antibody Test Proliferation
These antibody tests received a great deal of media attention over the past several months, as concerns rose about test quality of the assays flooding the market.
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Explore This IssueSeptember 2020
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The U.S. Food & Drug Administration (FDA) oversees issuance of emergency use authorizations (EUAs), intended to help make testing and treatments available to the public for serious or life-threatening conditions when no other approved, adequate alternatives are available. EUA approval is granted by the FDA based on information submitted by the companies, including information about test sensitivity and specificity—even if tests or treatments haven’t gone through the full testing needed for FDA approval.
In March, the FDA loosened its standards around the use of EUAs for serological antibody tests being developed in commercial labs. The FDA began allowing such tests to be marketed without first applying for an EUA, as long as companies notified the FDA and provided certain labeling notifications. For example, labeling had to disclose the tests were not FDA approved and specify they should not be used for diagnosis. The FDA also did not authorize any antibody tests to be released or marketed for home use.9
Ninety to 100 percent of adults have antibodies to common coronaviruses, a potential source of false positivity.
Some companies applied for EUAs and had them granted. Others began marketing such tests without applying for EUAs. Despite the labeling requirements specified by the FDA, many companies began marketing their products inappropriately. Some companies marketed their products as diagnostic tests for COVID-19.6 Other tests were falsely labeled as being FDA authorized or FDA approved, when an EUA had not been granted. Some were inappropriately advertised for at-home testing.10
Concerns also arose about these tests’ reliability. An independent analysis by the National Institutes of Health revealed that some tests were performing poorly.9
In May, the FDA released new guidance for commercial manufacturers. All such companies are now expected to submit official requests for an EUA to the FDA (including information about their validation results). This puts FDA guidance in line with similar parameters given to manufacturers of the molecular tests developed to test for active infection. The FDA also provided specific performance recommendations for specificity and sensitivity that should be met for commercial and non-commercial test developers.9
Non-commercial labs are regulated by a slightly different system, under the Clinical Laboratory Improvement Amendments (CLIA) by the Centers for Medicare & Medicaid Services. No sort of FDA authorization has been required for such tests, although they must be performed in a laboratory certified to perform high-complexity testing (as specified by CLIA). Such labs have been instructed to perform their own test validation and provide notification to the FDA of their tests. At this time, these labs are encouraged but not required to submit EUAs.9
The FDA has announced it will take action against tests falsely advertised as FDA authorized that have not been granted EUA status, and it has issued a limited number of cease and desist letters. The FDA also claims it has turned away illegitimate test kits at the border.11
However, the new policy does not specify additional actions the FDA will take if test developers fail to comply. Instead, the FDA “encourages states, hospitals and consumers to be on high alert and to make informed purchasing decisions regarding these tests.”11
On May 21, the FDA posted a list of antibody tests being removed from their earlier list under the new policy.12 Some manufactures have also voluntarily withdrawn their products from the market. Dr. Kadkhoda adds, “Initially it was a large number of lateral flow assays that had very questionable quality. At least those, for the most part, are gone now.”
Tests with Current EUA Approvals
The FDA has granted EUAs to tests of several types, including ELISAs and lateral flow assays. As of this writing, 39 COVID-19 antibody tests have been granted EUAs. The FDA provides a list of all tests granted EUAs, along with basic information about test characteristics and performance based on data supplied by the manufacturers.13,14
Although the FDA requires that companies validate their results with such parameters as specificity and sensitivity using known COVID-19 samples, data from PRNT tests demonstrating antibody neutralization are not required for EUAs. Dr. Calabrese notes that such tests are ordinarily performed as part of a standard process for FDA approval of a new test.