The U.S. FDA’s device center has declared it will not review emergency use authorization (EUA) requests for lab-developed tests (LDTs) for the COVID-19 pandemic, but on the agency’s most recent town hall, on Oct. 14, FDA officials were uncertain as to whether labs should file those EUAs, leaving labs in a state of limbo yet again.

Tim Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health, said on the Oct. 7 town hall that the agency would decline to review EUA submissions from clinical labs for their tests for the COVID-19 pandemic. Stenzel essentially recited the update to the FAQ in making the announcement and offered no additional insight into the question. That policy change followed the rescission order issued by the Department of Health and Human Services (HHS) in August declaring the FDA had no statutory authority to regulate LDTs in most instances, although the HHS notice gave no indication at that time that the FDA would cease reviewing EUA filings for LDTs.

Stenzel has said on several occasions, however, that OIR is struggling to keep pace with the flow of EUA submissions, a predicament he alluded to on the Oct. 14 town hall. He said the agency had received more than 2,400 EUA filings in total as of the end of September, adding, “we are making decisions as soon as we can.” The comment was in response to a question about processing times for EUA filings, and Stenzel acknowledged that the FDA has a triage system in place to prioritize the applications. The caller noted that some filings are processed in six days whereas others are still in queue after 100 days and counting.

On the question of whether labs should file EUAs despite the absence of any FDA intent to review them, Toby Lowe, associate director of OIR, said, “we’re generally not prioritizing review of LDTs,” adding that the Oct. 7 update to the FAQ is more recent than any FDA guidance on the subject. Stenzel said the agency is working on “some additional clarification in the FAQS, and this is a good question for us to potentially address,” given the discordance between the FAQ and the prior policy.

FDA spokesman James McKinney told BioWorld that Stenzel’s comments on the Oct. 14 town hall were intended to confirm that the agency’s guidance for LDT EUAs “does not reflect the most recent update from HHS” regarding the agency’s statutory authority. However, McKinney said an update to the FAQ “will likely be helpful” in providing greater clarity as to the agency’s stance.

BioWorld reached out to the American Clinical Laboratory Association for clarification, but received no response. Whether the FDA is amenable to a resumption of reviews for EUA filings for LDTs after the backlog is eliminated is not clear.

Retest still advised for any positive antigen tests for screening

Stenzel said the use of antigen tests as a screening mechanism in an asymptomatic population is backed by mixed data. The data suggest that in some cases, viral levels as determined by cycle thresholds are similar between those who are symptomatic and those who are not, but in others are “very different,” he said. The lack of clarity on the question has impeded the agency’s efforts to devise a policy.

A test developer can use one of several methods to validate an antigen test for asymptomatic screening, such as comparing the test to another high-sensitivity test that already enjoys authorization, and Stenzel said the agency is amenable to the use of banked samples to validate the candidate test. The question arose in the context of state officials in Nevada who ordered nursing homes to halt the use of an antigen test for nursing home screening, and Stenzel noted that physicians are within their professional authority to order the use of an antigen test off label. He said also that the Centers for Medicare & Medicaid Services has committed to pay for such testing.

Stenzel said the predicament with false positives in Nevada was difficult to avoid, given that false positives are not infrequent when prevalence of COVID-19 is low. He pointed out that the agency has recommended that anyone testing positive via an antigen test be repeat tested by a different test, a policy he said applies to all test types. Assistant Secretary of Health Brett Giroir advised Nevada state officials that their ban on the use of point-of-care antigen tests in nursing facilities flies in the face of EUAs issued for the tests and is preempted by federal law. The state’s concerns regarding positive predictive values for the test are “based on speculation” and may cost lives, Giroir said.

Stenzel said that holders of EUAs for direct antigen tests may have to file a new EUA package when moving the test to a high-throughput system for multi-analyte testing. This might require a new effort to establish analytical validity, and there is an interest at the FDA in ensuring that a reworked test for multiple pathogens doesn’t affect the performance for the SARS-CoV-2 virus. However, Lowe noted that any elements of the existing EUA that are still relevant can be referenced in the new EUA filing.

HHS pushes community testing program forward

The HHS reported recently that communities taking part in the federal testing surge effort will have access to a test that uses saliva samples obtained via a sterile container. The test, from Fluidigm Corp., of South San Francisco, uses a microfluidics platform that provides a level of accuracy comparable to other molecular tests for the SARS-CoV-2 pathogen.

The HHS statement said Waco, Texas, is the first area to offer this test under the Community-Based Testing Site program, and that three sites in Waco will have the test kits available. The Fluidigm is credited with a daily capacity of 6,000 runs, and was financed in part by the Rapid Acceleration of Diagnostics (RADx) program administered by the National Institutes of Health. The company has shipped 10,000 tests to Waco, but additional capacity is provided by clinical labs operating in the Waco area, HHS said.