The question of screening for the COVID-19 pandemic continues to absorb the interest of both the U.S. FDA and test developers, and Tim Stenzel, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health (OIR), said in a July 22 webinar that the FDA is “very interested” in a fingerstick test at the point of care for screening purposes, adding that the agency sees any such applications as a priority.

The weekly pandemic testing town hall has covered a number of subjects, and Stenzel said on the July 16 edition that the agency is interested in tests that pick up neutralizing antibodies. One of the points of emphasis for neutralizing antibodies is their utility in development of convalescent plasma treatments, the subject of an April 2020 guidance the FDA updated May 1.

One of the callers on the July 22 session called on behalf of physicians and other health care professionals in search of clarity on the question of screening. The question revolved around the FDA policy that allows fingerstick testing for two antibody isotypes (immunoglobulins M and G) without an explicit emergency use authorization (EUA). The presumption in this instance is that the test be labeled to indicate that it is not to be relied upon as the sole basis for a diagnosis.

Stenzel said the agency has allowed such tests to market on the proviso that the analysis be handled in a lab that is certified to conduct high-complexity tests under the CLIA regulations. A lab thus certified could set up a patient blood draw station, he said, adding that the agency has received no acceptable applications for a true point-of-care serology test using a fingerstick blood draw.

“We’re very interested in it, and as soon as someone submits acceptable data, we’ll authorize it as a high priority,” Stenzel said.

FDA pulls umbrella program for serology tests

Toby Lowe, associated director of OIR, said the agency has revoked the umbrella EUA for serology tests, stating that no tests have been added to this program in the three months since the agency instituted the program. “We have found it is more appropriate for us to individualize the EUAs for each specific test,” she added, which allows the agency to authorize tests for broader indications than would otherwise be possible.

Lowe said the agency believed the umbrella policy would streamline the administrative process, “but it turns out that doing the individual EAUs is a more streamlined process for us.” However, that does not suggest the underlying performance standards have changed, and Lowe said the FDA is still using the validation process conducted by the National Cancer Institute to corroborate the sponsor’s test validation.

Stenzel said that what was previously referred to as the template for home testing for molecular diagnostics and direct antigens is now designated as the template for non-laboratory testing “because the setting may not always be home,” a reference to testing at schools and workplace sites.

The FDA is working on updates to regular molecular testing templates to provide more information about pooling, such Dorfman pooling and pooling for swabs, Stenzel said. There are also updates for multi-analyte testing that covers the SARS-CoV-2 virus and other pathogens, such as one of the influenzas or the SARS-CoV-1 virus.

Stenzel said the FDA has received request to update the template for the direct antigen template with recommendations for multi-analyte testing, and as is the case with molecular testing, the sponsor can include targets such as influenza A and B along with SARS-CoV-1.

The FDA has been working with other federal agencies to adopt new criteria to assess some of the more novel technologies, and Stenzel said the FDA will provide a template that will deal with semi-quantitative, quantitative and neutralizing serology assays when the agency has developed a solid understanding of the underlying scientific issues.

Stenzel said a template for fully at-home testing will bear a title that addresses other locations for testing, adding that the agency receives queries about such a template on a weekly basis. The related umbrella template “is very far along,” he said, but he did not disclose when the template might surface other than to note that the FDA would issue it as soon as possible.

In response to a question about multiplex assays that report antibody isotypes separately, Stenzel said the agency has issued an EUA for a multiplex assay with IgM, but that he is unaware of any EUAs listing IgA. The agency expects to see a percent positive agreement of 70% for IgM with other analytes, while a 90% rate of positive agreement is the bar for IgG when part of a multiplex assay. The threshold for IgM alone is 90%, a set point he said was selected “to make these tests as useful as possible.”

The FDA has not yet issued an EUA for a multiplex assay for both IgA and IgM, but Stenzel said, “I expect we would still want to see at least one of those analytes to be positive to at least the 90% level.” The FDA has made no formal policy decision on this point yet, however.

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