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Dual 510k and CLIA Waiver by Application for In Vitro Diagnostic Tests

This guidance assists manufacturers in using the Dual 510(k) and CLIA Waiver by Application pathway for In Vitro Diagnostic (IVD) tests. It focuses on study design recommendations that can support both 510(k) clearance and CLIA waiver in a single submission. The guidance is particularly suitable for simple devices with fail-safe mechanisms, minimal pre-analytical steps, and subject to premarket notification requirements.

  1. Submit Pre-Submission to FDA to discuss planned study designs and comparative method selection
  2. Conduct comprehensive risk analysis and implement appropriate control measures
  3. Design and execute analytical studies to establish performance characteristics
  4. Perform comparison studies with untrained operators at representative sites
  5. Conduct reproducibility studies at minimum 3 sites with untrained operators
  6. Develop appropriate labeling for waived settings
  7. Prepare comprehensive documentation package including:
    • Device description demonstrating simplicity
    • Risk analysis results
    • Failure alert and fail-safe mechanisms validation
    • Flex studies results
    • Analytical studies data
    • Comparison and reproducibility studies results
    • Proposed labeling
  8. Submit complete Dual 510(k) and CLIA Waiver application package

Key Considerations

Clinical testing

  • Most IVD 510(k) submissions do not require clinical performance studies
  • Clinical studies may be needed for some devices (to be discussed with FDA in Pre-Submission)

Non-clinical testing

  • Analytical studies required including:
    • Analytical sensitivity (LoD/C5-C95)
    • Measuring interval
    • Analytical specificity
    • Linearity (quantitative tests)
    • Precision
    • Carry-over (if applicable)
    • Reagent stability
    • Sample stability

Human Factors

  • Testing should be performed by untrained operators representative of intended users
  • Studies should be integrated into daily workflow with multitasking
  • Testing sites should represent intended use settings
  • Subject populations should represent intended patient populations

Labelling

  • Must include instructions for use consistent with a “simple” device
  • Should be appropriate for waived settings

Safety

  • Risk analysis required identifying potential sources of error
  • Must include failure alert and fail-safe mechanisms
  • Flex studies demonstrating insensitivity to environmental and usage variations
  • Validation of control measures to mitigate risks

Other considerations

  • ISO 14971: Medical devices - Application of risk management to medical devices
  • CLSI EP21: Evaluation of Total Analytical Error for Quantitative Medical Laboratory Measurement Procedures
  • CLSI EP27: How to Construct and Interpret an Error Grid for Quantitative Diagnostic Assays
  • CLSI EP12: User Protocol for Evaluation of Qualitative Test Performance
  • CLSI EP17: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
  • CLSI EP05: Evaluation of Precision of Quantitative Measurement Procedures

Original guidance

  • Dual 510k and CLIA Waiver by Application for In Vitro Diagnostic Tests
  • HTML / PDF
  • Issue date: 2020-02-26
  • Last changed date: 2021-01-26
  • Status: FINAL
  • Official FDA topics: Medical Devices, Postmarket, 510(k), Premarket, CLIA (Clinical Laboratory Improvement Amendments)
  • ReguVirta summary file ID: cfb7faa2eaf7748de41163b9cd08427a
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