Diagnostic manufacturers are turning their attention to antibodies for those who have been vaccinated for the SARS-CoV-2 virus, and the U.S. FDA’s Tim Stenzel had some advice about this on the Feb. 10 testing town hall. Stenzel advised that developers think of such tests in the same vein as a companion diagnostic (CDx) in that these antibody test will have to be separately validated for each vaccine that is included in the test’s labeled claims.

The question of vaccine efficacy has been complicated by the emergence of several variants of the virus, and Stenzel tackled the question of validating tests for these new variants in a previous edition of the town hall. The key question for tests for response to a vaccine is sensitivity rather than specificity, and vaccine specificity will be key to quantitative antibody tests for the vaccines now being widely administered across the U.S.

Stenzel, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health (OIR), said a test developer will have to separately validate a test for the key antibodies generated by any vaccines that will be included in the product label. This is not dissimilar to validation of a CDx, in that a CDx is evaluated per a specific drug agent regardless of the target of the therapy.

Pre-test before vaccination recommended

Any validation study should include a test of the individual prior to vaccination, which will go toward demonstrating the test is not subject to a problematic level of false negatives. The validation study should depict the number of days that typically elapse before the vaccine generates a sufficient level of antibodies to confer immunity. Sponsors may want to lend as much specificity as to how they expect these parameters would play out before submitting any information for the emergency use authorization (EUA) filing, in order to economize both the developer’s and the FDA review team’s time and effort.

Toby Lowe, associate director of OIR, said unique device identifier (UDI) registration has not been typically required for tests granted access via the EUA program, although several EUAs have been authorized specifically with this requirement. Sponsors are at liberty to include a UDI index number for their tests, which is particular helpful for test kits shipped to clinical labs. Inclusion of UDI index numbers will help those labs fulfill an HHS lab reporting requirement related to UDIs as depicted in an HHS lab reporting guidance.

Stenzel said sponsors that are transferring ownership of a pending EUA submission should probably handle any related paperwork with the agency prior to the EUA filing. Post-authorization changes in ownership can be handled by notifying the lead reviewer for that filing.

One participant asked about the FDA’s agreement with NDA Partners LLC, of Rochelle, Va., to review lab-developed tests and whether the agency intends to resume review of individual EUAs for LDTs anytime soon. Stenzel had little more to say about this than to indicate the agency and the Department of Health and Human Services are discussing the predicament, although he did not directly reference the August 2020 HHS rescission order for LDT regulation.

Home-use serology template still in process

Home-use serology testing is the subject of a template that is in development at the agency, but Stenzel declined to predict when the FDA would publish the template. However, the agency will advise applicants about the agency’s current thinking about the validation requirements for such tests via the pre-EUA process.

Stenzel said the agency’s current thinking on validating an existing test for the novel variants of the SARS-CoV-2 virus may be best handled with the help of whole-genome sequencing. The agency is accepting applications for any subset of variants the developer would ask the agency to review. However, he said the agency would prefer that sponsors consider the prospect that new variants will emerge.

Any de novo applications for tests that were marketed under an EUA that come after a similar submission will be converted to a 510(k) and the difference in user fees will be refunded. Stenzel said the sponsor in this scenario would not have to revise and resubmit their dossier. The FDA is also still prioritizing submissions for tests that can meaningfully increase overall volume of testing, along with those that increase accessibility.