FDA Regulation of COVID-19 Testing Enters a New Phase

The public health emergency (PHE) is still in effect but the honeymoon has ended. The leniency that the U.S. Food and Drug Administration (FDA) has displayed toward COVID-19 tests and test makers through much of the coronavirus crisis has been replaced with a more business-as-usual approach. Simply stated, the agency is tightening up and increasing regulatory scrutiny over COVID-19 tests, including those that have received Emergency Use Authorization (EUA).

No More Mr. Nice Guy

Throughout the PHE, FDA officials have insisted that its extensive use of the EUA process and various measures to liberalize rules with regard to pooling, asymptomatic screening, at-home sample collection, non-laboratory setting validation and other aspects of COVID-19 test development and approval represent an expedient to bring desperately needed SARS-CoV-2 diagnostics to market rather than a fundamental change in regulatory approach and philosophy. But as the development of a robust pipeline for new tests obviates the need for flexibility, the agency has signaled its determination to resume normal scrutiny.

In a recent interview with Medscape magazine, Dr. Patricia Cavazzoni, Director of the FDA Center for Drug Evaluation and Research (CDER) acknowledged that EUA represents a “different sort of standard when it comes to deciding whether to make a therapeutic available.” At the start of the pandemic “we had nothing.” However, she continued, “we’re in a very different place now where we have therapeutics. . . And so now we’re in the space where our benefit/risk calculus also has to consider the fact that we have some effective therapeutics out there, and that obviously serves as context for how we look at the data.”

FDA Takes Actions Against COVID-19 Tests

Although they address COVID-19 therapeutics and clinical trials, Dr. Cavazzoni’s remarks apply equally to SARS-CoV-2 testing. Exhibit A is the agency’s recent spate of enforcement actions targeting test makers. It began in late May, when FDA issued a Class I recall, the most serious kind, of the Lepu Medical Technology SARS-CoV-2 antigen test and Leccurate SARS-CoV-2 antibody rapid test. The agency cautioned against using the products, which were sold directly to consumers, because of their high risk of false positives.

In August, FDA issued a warning letter to Vivera Pharmaceuticals for marketing unapproved COVID-19 tests. The agency claims it found offerings for a pair of unauthorized tests on the Mission Viejo, Calif.-based company’s websites, including the COVx-RDA Saliva Antigen Test and a COVx-RDA Nasal Antigen Test. Vivera’s COVID-19 test kits are considered adulterated and misbranded, the agency said, adding that it is taking urgent measures to stop the sale of such products during the pandemic.

Revocation of EUAs

Starting in late May, the agency has also revoked about a half dozen EUAs for COVID-19 tests. In most cases, these actions were undertaken in response to the company’s request. These revocations include (in chronological order):

• The RT-PCR assay developed by the US Centers for Disease Control and Prevention (CDC), the first COVID-19 test to receive EUA, after the agency actually withdrew the EUA, recommending that laboratories that were still using the test transition to a test that can differentiate the coronavirus from influenza viruses;
• Gravity Diagnostics’ Gravity COVID-19 Assay, which the company had retired in favor of a modernized test methodology;
• Curative’s Curative-Korva SARS-Cov-2 Assay, which received EUA in April 2020 as the PHE was beginning, but which was subject of an agency alert warning for false negatives earlier this year;
• BioFire Diagnostics’ BioFire Respiratory Panel 2.1, which subsequently gained de novo clearance, making EUA no longer necessary; and
• Guardant Health’s Guardant-19 COVID-19 assay, in response to the company’s request following its strategic decision to get out of COVID testing and return its focus to oncology.

Takeaway

We have entered a new chapter in FDA regulation of COVID-19 tests. Although the EUA channel remains very much intact, the agency is signaling its intention to return to normal review procedures and standards as early as conditions permit. In the meantime, test makers are also reviewing their own COVID-19 testing products and strategies. In some cases, as with Guardant Health, that means withdrawing from COVID-19 and refocusing on core products. Others like BioFire and Curative are going in the other direction in favor of product evolution and improvement and shedding early EUA products along the path to innovation.