A number of controversies have swirled around the U.S. FDA’s handling of the COVID-19 pandemic, including the question of the emergency use authorization (EUA) program for testing. The FDA’s Tim Stenzel said on an Aug. 26 testing town hall that he would not answer questions about the rescission order for FDA regulation of lab-developed tests (LDTs), but also said, “we are simply overwhelmed” with EUA filings for testing.

Several callers to the town hall complained about lag times in the FDA’s handing of EUA submissions, including one caller who indicated that he had contacted the FDA in connection with the Yale Salivadirect EUA. The caller said he had received a “very terse, if not dismissive response” in connection with an inquiry. Stenzel responded to one such complaint about lag times by noting that contract manufacture of test components should not hold up test distribution pending an FDA review of that contract manufacturing site’s compliance data.

The Department of Health and Human Services said in the rescission order that the FDA would no longer require any sort of premarket submission from clinical labs for lab-developed tests for the pandemic, but the underlying language suggests a durability intended to outlast the pandemic. One issue associated with the order, however, is that LDTs that do not go through the EUA or a conventional premarket review process will not enjoy immunity from product liability litigation under the public health emergency.

Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health (OIVR), said the non-lab EUA template for home testing currently offers details regarding molecular and direct antigen tests, but that the agency is interested in EUAs for serology tests for this environment. The agency is interested in hearing from test developers regarding methods of recording data drawn from these home tests as well, however, a consideration that appears in the template. He vowed that the data collection consideration will not affect the agency’s review of home testing technologies.

For contract manufacturing of items that are marketed under an existing EUA, Stenzel said a developer should notify the lead reviewer, who will update the EUA, adding that any formalities and associated paperwork could be handled later.

Mina controversy, direct antigen tests revisited

One of the callers to the Aug. 26 town hall made reference to Harvard epidemiologist Michael Mina, who has argued that the FDA’s approach to testing is deficient due to a bias toward diagnostic rather than surveillance testing. The caller noted that there are several antigen tests that are very specific at a cycle threshold (CT) of 30 and below, but that these tests do not meet the FDA requirement of 90% specificity compared to PCR. Stenzel said the recommended sensitivity for non-lab prescription tests with home sample collection is 80%, but that this figure rises to 90% if there is no prescribing health care professional.

Of the three direct antigen tests authorized to date, one met the 80% set point while the other two reached 90% or better sensitivity, but Stenzel said the agency does see value in a test that picks up asymptomatic individuals when CT values exceed 30. Validation of a test for this purpose will likely have to include symptomatic individuals as well because of the difficulty of establishing when asymptomatics will begin to shed virus, he said, adding that the concerns regarding antigen test sensitivity revolve in part around the difference in performance compared to PCR when viral loads begin to drop.

One of the EUA direct antigen tests is authorized for up to 12 days post-onset of symptoms, which Stenzel said “is quite long” for a direct antigen test. There are several non-instrumented, direct antigen tests in the EUA pipeline as well, and the FDA expects at least some “will be highly successful,” Stenzel said.

Tongue scrapings should be compared to NP

On the Aug. 12 town hall, the most recent transcript posted by the agency, Kris Roth, a supervisory chemist at the Center for Devices and Radiological Health, said samples drawn from tongue scrapings should probably be compared to nasopharyngeal (NPs) samples so long as the two samples are taken within 24 hours or so of each other.

The agency has a template for validation of alternative sample types, and while there are no recommendations specific to tongue scrapings, Roth said the discussion of respiratory samples may offer the best insight into validating tongue scrapings. A test developer that wants to add pooling to an EUA-authorized test does not have to repeat the steps needed to evaluate sensitivity and specificity, although developers may want to include data that depicts any possible shift in sensitivity.

One caller said their submission has been in queue for more than three months, and had been assigned a reviewer since the second half of June, although an agency response was still absent. Complaints have routinely surfaced about the backlog under the EUA program, perhaps one of the motives for the HHS declaration that lab-developed tests would no longer be forced into an FDA review cycle.

CDC tweaks testing guidelines

The U.S. CDC has posted a revision to its testing advisory, an update that drew blistering criticism in the media. Previously, the agency had stated that testing was recommended for all who are “close contacts” of anyone with a confirmed infection, and that such testing be conducted quickly. However, the Aug. 24 update states that testing should be done for “people who have had close contact” with someone with a confirmed infection. The term “close contact” is defined in the update as anyone who was within six feet of an infected individual for at least 15 minutes.

The CDC website was updated with an Aug. 26 statement quoting director Robert Redfield as saying that a new report reinforces the value of mitigations in suppressing COVID-19 transmission. The associated Morbidity and Mortality Weekly Report for Aug. 26, labeled an early release, addresses rates of transmission in four overnight camps in Maine during which more than 1,000 campers were in attendance. The report cites the instance of camps in Georgia that led to proliferation of the SARS-CoV-2 virus in the absence of mitigations, but added that only three asymptomatic cases were identified at the Maine camps post-arrival. Redfield said the outcome demonstrated the value of conventional non-pharmacological measures in thwarting the spread of the virus.