USFDA Guidance: Validation of IVD Devices for Emerging Pathogens During Public Health Emergencies
The U.S. Food and Drug Administration (FDA) has issued a final guidance titled Validation of Certain In Vitro Diagnostic Devices for Emerging Pathogens During a Section 564 Declared Emergency, providing recommendations for manufacturers developing diagnostic tests during public health emergencies.
Issued on 10 November 2026, the guidance replaces the draft published on 7 January 2025. It outlines validation recommendations for certain in vitro diagnostic devices (IVDs) intended to detect emerging pathogens during an applicable emergency declaration under Section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
The guidance applies to data submitted in pre-Emergency Use Authorization (pre-EUA) submissions, EUA requests, and tests offered under applicable FDA enforcement discretion policies.
Key Recommendations
1. Scope and Applicability
The guidance covers diagnostic tests, including molecular and antigen tests, intended to detect pathogens causing serious or life-threatening infectious diseases during an applicable Section 564 declaration. It applies across different stages of an outbreak and recognises that validation approaches may need to change depending on the availability of clinical specimens, testing materials and public health needs.
Serology and antibody tests intended to assess adaptive immune responses are generally outside its scope.
2. Clinical Performance Evaluation
FDA recommends evaluating test performance using clinical specimens representative of the intended-use population and testing environment. Prospective studies using natural clinical specimens and an appropriate comparator method are preferred.
Where suitable clinical specimens are available, FDA generally considers at least 30 positive and 30 negative specimens appropriate for certain viral nucleic acid tests using established technologies. The study should assess positive percent agreement (PPA), negative percent agreement (NPA) and their corresponding 95% confidence intervals.
3. Alternative Specimens During Early Outbreaks
When natural clinical specimens are unavailable during the initial stages of an outbreak, manufacturers may consider archived positive and negative specimens or contrived specimens prepared using negative human clinical matrix.
Synthetic materials may also be considered when pathogen stocks are unavailable, provided they closely mimic the natural target material. Where validation relies on contrived or synthetic specimens, FDA may include a condition of authorization requiring a post-authorization clinical performance evaluation using natural patient specimens when feasible.
4. Analytical Validation Testing
The guidance recommends analytical validation covering key performance characteristics, including:
Limit of Detection (LoD): Establishes the lowest concentration consistently detected by the test. The final LoD is generally confirmed using at least 20 replicates, with at least 95% detection.
Inclusivity: Evaluates the ability to detect relevant pathogen species, isolates and variants. Molecular tests should include in-silico sequence analysis and wet testing where appropriate. FDA recommends monthly evaluation of inclusivity for antigen tests to monitor emerging variants.
Specimen Stability: Evaluates specimen performance under proposed storage, transport and temperature conditions.
Additional Testing: May include cross-reactivity, microbial interference, endogenous and exogenous interference, carry-over and high-dose hook-effect studies, depending on the test type and risk.
5. Software, Safety and Usability
Manufacturers should address basic safety, software validation, cybersecurity and electromagnetic compatibility (EMC), where applicable. For point-of-care and home-use tests, usability studies should demonstrate that intended users can correctly perform the test workflow.
User comprehension studies should also assess whether lay users understand critical instructions, warnings and test results. FDA recommends clear instructions, supported by pictures and diagrams, particularly for tests intended for home use or untrained operators.
6. Change Protocols
Manufacturers may consider developing change protocols for anticipated modifications to an EUA-authorised test. These protocols should describe the proposed changes, validation activities, acceptance criteria and any required labelling updates.
When reviewed by FDA and included in the initial authorisation, changes implemented in accordance with the protocol may be covered by that authorisation, subject to the applicable conditions.
7. Additional Considerations for Specific Test Types
The guidance also provides recommendations for specific diagnostic formats:
Multi-Analyte Panels: Each analyte should be validated, with consideration of cross-reactivity and microbial interference between targets.
Home Collection and Home-Use Tests: Testing should consider the complete user workflow, specimen collection, transport, safety, accessibility and clear instructions.
Point-of-Care (POC) Tests: Clinical performance should be evaluated in representative settings by intended users. For tests intended for CLIA Certificate of Waiver settings, the guidance provides recommendations for study sites, operators and near-LoD testing.
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