The next phase of testing for the COVID-19 pandemic will hopefully include the roll-out of tests for neutralizing antibodies for the SARS-CoV-2 virus, but there are some roadblocks. The FDA’s Tim Stenzel said the agency has a limited amount of information to offer regarding emergency use authorizations for these tests, a predicament that might not resolve until several applicants are in and the agency can see some information that will aid in development of performance and validation standards.
Stenzel, the director of the U.S. FDA’s Office of In Vitro Diagnostics and Radiological Health (OIR), acknowledged on the July 15 diagnostic town hall that the existing emergency use authorization (EUA) templates for testing offer little useful information about neutralizing antibody tests.
“We are very welcoming of EUA applications for neutralizing antibody tests,” Stenzel said, which have several uses, including determining whether a patient is a good donor for convalescent plasma. There are two types of assays that include neutralizing claims. One is a quantitative, or titered, serology test that establishes a correlation with a neutralizing reference method. This assumes that a certain titer or cutoff demonstrates a significant overlap between the detection of antibodies and a high level of neutralizing antibodies. Stenzel said this is not a direct neutralizing antibody assay.
“There are various ways to do this testing more directly,” Stenzel said, which includes semi-quantitative testing. In this instance, a minimum titer may be required to determine whether significant neutralizing antibodies are present, but in either case, the sponsor should compare the results to a validated reference method to establish a correlation with a neutralizing antibody that has some data behind it.
The FDA’s existing templates do not offer much detail on validation, but Stenzel said that the more detail EUA applicants can provide, the more the agency will have to go on in its effort to fill in the blanks in its templates. He said this is a relatively new area of review for the FDA, and before more feedback can be offered for a template, “we want to understand the assays that we first see in submission, understand their performance, [and] understand how we can establish truth to a reference standard.” At that point, the agency will be in a position to develop recommendations on the basis of those applications.
Stenzel said the agency has not authorized any assays for correlation or actual neutralizing antibodies, but said, “there’s very strong interest and we welcome them now, of course.” Saliva could be a sampling medium for measurement of immunoglobulin A (IgA), which might correlate well with some types of immunity. However, Stenzel said the FDA has no recommendations for validating such a test, another point of interest for which the agency seeks feedback.
Redfield urges hospital COVID data be sent to HHS system
The controversy over the response to the pandemic by various parts of the U.S. Department of Health and Human Services was lent new life with the announcement that the department is asking hospitals to send their pandemic-related data to an HHS data system. However, Robert Redfield, director of the CDC, attempted to assuage concerns that CDC will be sidelined as a consequence of the change.
The HHS press release explaining the shift includes Redfield’s prepared remarks, which include the observation that the CDC National Health Safety Network (NHSN) is set up to track antibiotic resistance. Redfield said the department developed the HHS Protect system in April as a method for combing through data from the CDC and other systems in both the public and private sectors. The data that had been reported into this new HHS system had arrived via the CDC mechanism, directly from the states, and from the Teletracking system, but Redfield said hospitals are now urged to send their data directly to either the Teletracking system or to HHS Protect.
The change reduces duplicative reporting, Redfield said, adding that the streamlined reporting process should not only reduce confusion for hospitals, but “enables us to distribute scarce resources using the best possible data.”
The Teletracking system is also pliable enough to allow the addition of data fields for treatments that are used on patients, but Redfield said the NHSN had to be sidelined for now in order to speed up the data collection and analysis effort. He said, nonetheless, that “no one is taking access or data away from CDC.”
The switch allows CDC to focus its resources on protecting the residents of nursing homes, and Redfield said the agency will have access to the data aggregated by HHS Protect, as will state and local officials. This change will accelerate access to data, which will in turn enable the federal health systems’ response to the pandemic, Redfield said, adding that the change “has no effect on CDC’s ability to use this data and continue churning out the daily data.” This applies also to other reports and CDC guidance for the pandemic.
Redfield said the need to modernize CDC data systems was an issue he recognized immediately upon his arrival at CDC, and HHS chief information officer Jose Arrieta noted that NHSN had been receiving input from roughly 3,000 hospitals prior to the outbreak of the pandemic. That is less than half the 6,200 hospitals in the U.S., Arrieta said, adding that Teletracking added another 1,000 hospitals to the federal government’s data stream. HHS Protect brough on board another 2,000 hospitals in 20 states, and these additional capabilities “provided increased visibility rapidly,” he said.