Impact of Viral Mutations on SARS-CoV-2 Tests: Evaluation and Monitoring Recommendations
This guidance provides recommendations for evaluating the potential impact of emerging and future viral mutations of SARS-CoV-2 on COVID-19 tests. It applies to: - Developers of SARS-CoV-2 molecular, antigen, and serology tests with EUA - Developers whose tests fall within FDA's policy for COVID-19 tests - Developers pursuing EUA for COVID-19 molecular, antigen, and serology tests
Recommended Actions
- Implement routine monitoring of viral mutations through sequence database analysis
- Design test with multiple targets when possible to minimize impact of mutations
- Develop and document procedures for:
- Evaluating impact of new mutations
- Conducting melting temperature calculations
- Performing wet testing when needed
- Notifying FDA of significant findings
- Update test labeling to include:
- Limitations regarding variants
- Time period and location of clinical validation
- Performance variation statements
- Create plan for:
- Routine monitoring of mutations
- Assessment of mutation impact on test performance
- Investigation of performance changes
- Communication with FDA
- Maintain records of all evaluations and be prepared to submit to FDA upon request
- Engage with FDA early during test development regarding approach to variant impact evaluation
Key Considerations
Non-clinical testing
- Perform sequence alignment of primer/probe sequences with public SARS-CoV-2 genomes
- Evaluate hybridization changes when mutations are identified
- Conduct melting temperature calculations
- Perform wet testing with clinical samples or synthetic RNA targets when mutations are identified
- Establish limit of detection for both original and mutated targets
Labelling
- Include statements about time period and geographic location of clinical specimens used in evaluation
- Indicate that clinical performance has not been established for all circulating variants
- State that performance may vary depending on variants and their prevalence
Other considerations
- Design tests to minimize impact of viral mutations on performance
- Include multiple targets when possible to provide redundancy
- Routinely monitor for viral mutations that may impact test performance
- Notify FDA if mutations potentially change benefit-risk profile
- Consider impact of mutations on antigen and serology test performance
- Develop monitoring plan for new genetic mutations and variants
Relevant Guidances
- Content of Premarket Submissions for Device Software Functions
- Design Controls for Medical Device Manufacturers
- In Vitro Diagnostic Devices for Detection and Differentiation of Influenza Viruses - Performance Testing and Validation Requirements
- Dual Use Molecular Diagnostic Instruments with FDA-Approved and Non-Approved Functions
Related references and norms
- 21 CFR 866.3981: Devices to detect and identify nucleic acid targets in respiratory specimens
Original guidance
- Impact of Viral Mutations on SARS-CoV-2 Tests: Evaluation and Monitoring Recommendations
- HTML / PDF
- Issue date: 2023-01-12
- Last changed date: 2024-12-30
- Status: FINAL
- Official FDA topics: Medical Devices, Premarket, Coronavirus, IVDs (In Vitro Diagnostic Devices)
- ReguVirta summary file ID: d537c015312b49605abc3b147938cfd6
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