The U.S. FDA is still struggling to keep up with the volume of diagnostic emergency use authorizations (EUAs), but it is not for want of effort. Tim Stenzel, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health (OIR), said on the Feb. 3 testing town hall that the agency is processing nine such applications per day, a big jump over the rate of one per day in the early weeks of the COVID-19 pandemic.

Stenzel said, “we continue to see an amazing number of submissions,” which total to “many hundreds on a monthly basis.” He said that among the nine or so decisions per day over the previous week were both new and supplemental/amended EUAs. The agency does not typically publicize negative decisions, but Stenzel said, “we’re working harder and faster than ever, with more people.”

Stenzel said developers should monitor smartphones for updates that might affect the performance of a smartphone app used to provide interpretation of an at-home test. He said any test entities that are developing such an app will hopefully have a relationship with the manufacturer of the phone so the developer can be advised of impending updates to the phone’s operating system (OS).

The agency will want to be made aware of any performance problems with that app generated by updates to the OS, but developers are advised that they should include procedures for change controls in their EUAs to handle these situations.

Cross-reactivity a thorn for breath tests for screening

Stenzel said the agency’s thinking on breath tests as a screening mechanism is still being developed, but noted that the FDA would want to see a relatively high sensitivity in the asymptomatic population. Due to the lack of regulatory experience, the agency may want to see more positives in the asymptomatic population in the study of the device than the agency might ask of studies for molecular or antigen tests, although the difference in the required volume of enrollment for these patients will not be especially conspicuous.

Stenzel added that the problem of cross-reactivity is particularly difficult for a breath test since the analyte is not the virus itself. In one such instance, a developer is using volatile organic compounds to serve as an indicator of a positive test result. One practicable way to control for cross-reactivity would be to study the candidate system against a respiratory panel test and non-respiratory test on symptomatic individuals.

These alternative tests would have to be authorized under an EUA, but Stenzel advised that only 5% to 10% of the symptomatic patients who enroll in a study will have a SARS-specific pathogen. A solid-performing respiratory panel will disclose which of the enrollees is positive for COVID-19, but Stenzel said this is only the agency’s current thinking and may be modified as the science evolves.

The FDA does not have a fixed set of standards for smartphones that use a camera lens to aid in the interpretation of a diagnostic effort, but Stenzel said the agency is working with developers on these issues. At present, the agency is aware of variability in the performance of the components, such as smartphone CPUs and lenses, but he said he could not recall whether the agency had authorized or otherwise approved or cleared a smartphone reader for this type of application in any intended use.

The agency often learns more about a novel approach from its initial encounter with a premarket application than would otherwise ever occur, although Stenzel noted that the Center for Devices and Radiological Health has a research office that could investigate this question. He recommended that developers contact the agency before putting too much effort into such an EUA to economize the developer’s time and financial resources.

Updates to existing EUAs continue to roll in

The FDA has a number of new emergency use authorizations for diagnostic and other testing purposes, and has added 12 new or updated EUAs for diagnostic testing since Jan. 26. The most recent of these is an update to the real-time fluorescent reverse transcriptase test by BGI Genomics of New York, although the U.S. government’s Sandia National Laboratories is also among the entities that received a new or updated molecular testing EUA.

The list of new or updated antigen tests is not as heavily populated, however. Only five EUAs for antigen tests have been issued as a new or updated EUA since the beginning of 2021, including the Carestart test by Access Bio Inc., of Somerset, N.J. Stenzel noted during the Feb. 3 town hall that antigen tests are some of the more difficult test types to develop and validate. Interestingly, the umbrella EUA for lab-developed tests is still active, although this includes only two new or updated tests, such as the Jan. 29 update for a PCR test by CSI Labs Inc., of Alpharetta, Ga.