Diagnostic Update: Previewing policy changes for antigen tests and monkeypox products

At a monthly town hall with FDA Diagnostics Office leadership, regulators talked about upcoming changes to the expectations for Covid-19 antigen tests and previewed a potential policy shift for monkeypox products.


  • The main update at the August town hall was a preview of impending antigen test policy changes.

    • Antigen tests and sensitivity; Early in the pandemic, the FDA established that the relative lower sensitivity associated with at-home antigen tests could be offset through a serial testing strategy. In effect, the agency has allowed over-the-counter (OTC) antigen tests for Covid-19 to be authorized even with a lower sensitivity per administration of the test, so long as the cumulative sensitivity of multiple tests undertaken in a set amount of time would meet the agency’s performance baseline. Over time, though, it appears that antigen test performance has taken a hit. As AgencyIQ has previously discussed, CDRH Office of In Vitro Diagnostics (OHT7, previously known as OIR) Director Tim Stenzel has declined to tie the increase in the percent of low positives (i.e., individuals with Covid-19 presenting with a low viral load) to the omicron variant of the virus specifically; research to identify a specific driving factor of the issue is still underway.
    • On August 11, CDRH put out a safety communication about antigen tests for Covid-19. That announcement highlighted emerging concerns about the sensitivity of antigen tests, stating that the agency was urging “repeat, or serial testing when people get a negative result with an at-home COVID-19 antigen test,” including recommending additional testing over a longer period of time. While current tests are authorized (e.g., the BinaxNOW Ag Card Home Test) to confirm a negative result after two tests, the new recommendation urges asymptomatic individuals using OTC antigen tests take three tests, each 48 hours apart, to confirm a negative result (two in 48 hours for symptomatic individuals). Per that alert, the agency “encourage[d] at-home COVID-19 antigen test developers with a current Emergency Use Authorization (EUA) to engage with us” about leveraging new evidence.
    • Today, Deputy Microbiology Branch Chief Kris Roth previewed new actions for EUA tests. The safety communication cites research currently in pre-print and not yet peer-reviewed from UMass Chan Medical School (and supported by NIH’s RADx Program). The results of that study indicate that increasing testing to 3 times, 48 hours apart was more likely to capture infections, with the updated serial testing strategy detecting over 75% of infections in asymptomatic individuals, rather than about 60% from the two-test method. As Roth stated during the town hall today, OHT7 thinks that the study “can be leveraged” to improve performance of the existing EUA authorized at-home antigen tests.
    • Industry should keep an eye out for more information. Going forward, it appears that OHT7 is currently developing a policy that might require updated labeling for OTC or at-home antigen tests, including those that already have EUAs. While Roth maintained that OHT7 believes it is “critical to public health that these tests remain on market,” changes to the tests’ labeling are likely going to be needed to implement a new testing strategy, based on the UMass study.
    • What could the policy change look like? The specifics of what OHT7 will be asking developers and manufacturers to do remains to be seen – and appears to still be under consideration. Theoretically, changes could include updates to the labeling of OTC/at-home antigen test products to incorporate the updated best-practices on serial testing strategies based on the evidence and study designs from the UMass study. The agency has done something conceptually similar once before, rolling out a mass update to its Conditions of Authorization for EUA tests to incorporate a Condition that they assess the impact of viral variants on their test performance.
    • It appears that OHT7 wants to roll the policy out cohesively. While the Office has not yet released its plan, it appears that the plan is “to communicate with all antigen tests developers at the same time,” rather than to work one-on-one with antigen developers in advance, said Roth, and “that’s part of our communication plan.” For now, it doesn’t appear that the policy is fully ready for prime time – “we’re still discussing what the plan is [going] forward for everybody,” he acknowledged.
    • Anticipated timing of such a policy roll out; “More information will be available soon, and we will provide updates on this call throughout this transition period,” said Roth. Notably, the Covid-19 diagnostics town hall calls’ frequency has declined in recent months, so the next town hall call is September 28th – which could provide a good indicator of when OHT7 intends to have such a policy change ready.
    • Speaking of transitions, there is still no word on when the transition away from emergency authorities could be coming for diagnostic products. Operationally, if it appears that CDRH is gearing up for a (labor intensive) shift in policy for OTC antigen test products, this could mean that regulators are not thinking that they will need to make a transition in the near term.

    A quick update on monkeypox

    • Quick reminder: The town hall calls are intended to focus on Covid-19. However, OHT7 leadership has provided some brief updates on the monkeypox outbreak since June, when the outbreak became of concern to U.S. regulators. At the July town hall, OHT7 Director Stenzel not only outlined the current testing landscape for monkeypox but also provided operational updates for his office, including confirmation that OHT7 has established a monkeypox division.
    • Emergency declarations for the monkeypox outbreak: In early August, the White House declared the monkeypox outbreak a public health emergency (PHE) under section 319 of the Public Health Services (PHS) Act. On August 10, FDA and HHS announced a new declaration that circumstances exist justifying emergency use (i.e., “EUA declaration”), which opens the EUA pathway for specific products, for monkeypox vaccines – announced simultaneously with a new EUA update for the JYNNEOS vaccine. However, such a declaration, which comes from a different authority than the PHE (section 564 of the Food, Drug and Cosmetics (FD&C) Act), has not come for diagnostics.
    • The current monkeypox testing landscape; There is an FDA cleared diagnostic for orthopoxvirus, sponsored by the Centers for Disease Control and Prevention (CDC), which can detect monkeypox, cowpox, and vaccinia viruses. That diagnostic is currently in use in the CDC and Defense Department’s Laboratory Response Network (LRN), a “national bioterrorism preparedness initiative” that qualifies certain member public health/DoD laboratories to respond to certain high-risk “agents of concern.” As concerns about monkeypox – and incidence of infections – have spread in the U.S., CDC/FDA have worked to expand access to the CDC assay, which is now in use in four commercial lab networks (i.e., non-LRN labs) as well. According to reporting by POLITICO, the White House indicates that 80,000 such tests can be run in the U.S. per week.
    • Previewing an emergency policy for monkeypox diagnostics. As AgencyIQ has previously discussed, POLITICO recently reported on a potential path forward for monkeypox diagnostics. At the time, regulators floated a potential return of the notification pathway, in which developers would need to individually validate their tests and then send that validation data to the FDA at a later date. Notably, this reporting came after OHT7 Director Stenzel reminded developers that the agency’s existing laboratory-developed test (LDT) enforcement discretion policy was in place for these products – although notably, that enforcement discretion has traditionally come to an end upon the declaration of a PHE – and therefore indicated to those developers that there would be a reasonable expectation to have a path to bring a test to market without seeking full 510(k) clearance.
    • While there’s still no EUA declaration specifically for monkeypox diagnostics, OHT7 Associate Director for Regulatory Programs Toby Lowe today confirmed that the agency does not actually need a 564 declaration in order to receive and review pre-EUAs, encouraging developers who are considering monkeypox product development to send in questions through that mechanism. For developers interested in monkeypox tests, the pre-EUA pathway appears to be open to seek feedback from the agency.
    • What’s next? If Lowe is encouraging pre-EUAs for monkeypox tests, it seems likely that OHT7 is expecting the EUA pathway to become available for these products. While there is no word yet on when such a declaration would be made, this would likely put additional pressures on the already capacity-stretched OHT7 – and have trickle-down implications for IVD developers who have already faced two years of regulatory delays due to the pandemic.

    Housekeeping: The town hall schedule

    • The diagnostic town hall meetings have been a mainstay of the Covid-19 pandemic. The town halls provide a forum for test developers to elevate practical or policy issues directly to leadership in CDRH’s Office of In Vitro Diagnostics (OHT7, previously OIR), including Office Director Tim Stenzel, Associate Director for Regulatory Programs Toby Lowe and Deputy Division Director for Microbiology Devices Kris Roth. In the summer of 2022, the cadence of the meetings decreased to once per month.
    • Going forward, the monthly schedule is still on. The town halls will be held on the fourth Wednesday of the month for the foreseeable future.
    • The next two dates: September 26 and October 28. Further dates have yet to be announced.

    To contact the author of this item, please email Laura DiAngelo.
    To contact the editor of this item, please email Kari Oakes.

    Key Documents and Dates

Copy link
Powered by Social Snap