FDA Influenza IVD Performance Guidance

01 What the document says

This guidance sets out the data FDA recommends for Class I and Class II premarket submissions for tests that detect influenza viruses or distinguish influenza A from B. It was finalized in 2011 after a 2008 draft and remains the current version. It applies to antigen-based rapid tests and to nucleic acid-based tests alike, with some recommendations specific to each technology.

The analytical section describes limit of detection studies across representative circulating and historical strains, analytical reactivity against a panel of influenza strains, cross-reactivity and microbial interference against other respiratory pathogens and normal flora, interference from common substances found in respiratory specimens, and reproducibility. The guidance includes lists of strains and organisms FDA recommends and a suggested format for presenting cross-reactivity data, which is why it is still consulted when planning bench work.

The clinical section recommends prospective studies using fresh specimens collected from symptomatic patients during the influenza season, at several geographically distinct sites, with performance calculated against an appropriate reference method and reported separately for each specimen type and for influenza A and B. It also discusses the limited role of archived or frozen specimens, the need for a plan when circulating strains change, and labeling statements about the effect of prevalence on predictive values.

Separately from this guidance, FDA later reclassified antigen-based rapid influenza tests into Class II with special controls that include minimum clinical performance criteria against a molecular or culture comparator. Sponsors of antigen tests should read this guidance together with that classification regulation.

02 What it means when you plan a study

• Clinical enrollment is tied to the influenza season, so a study that misses the seasonal peak may need a second season; site selection across regions hedges against local timing differences.
• Fresh prospective specimens are the expectation; archived specimens are at most a supplement, which means specimen collection, transport, and reference testing must run in parallel in real time.
• The comparator must be a method FDA considers appropriate for the claim; in current practice that is typically a cleared molecular assay or viral culture, and the comparator's own specimen requirements shape the collection protocol.
• Sample size depends on how many influenza A and influenza B positives are collected, and B positives are often the limiting factor in a mild season; plan enrollment targets by subtype, not just total positives.
• Analytical reactivity panels need to reflect currently circulating strains, so the bench study plan should be refreshed close to the clinical season rather than copied from a prior submission.

03 Pathways it applies to

• 510(k) Clinical Studies
• CLIA Waiver Studies
• Dual Submission Studies

Source document: Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection or Detection and Differentiation of Influenza Viruses (fda.gov).