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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

  1. Implement routine monitoring of viral mutations through sequence database analysis
  2. Design test with multiple targets when possible to minimize impact of mutations
  3. Develop and document procedures for:
    • Evaluating impact of new mutations
    • Conducting melting temperature calculations
    • Performing wet testing when needed
    • Notifying FDA of significant findings
  4. Update test labeling to include:
    • Limitations regarding variants
    • Time period and location of clinical validation
    • Performance variation statements
  5. Create plan for:
    • Routine monitoring of mutations
    • Assessment of mutation impact on test performance
    • Investigation of performance changes
    • Communication with FDA
  6. Maintain records of all evaluations and be prepared to submit to FDA upon request
  7. 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

  • 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
This post is licensed under CC BY 4.0 by the author.