Post

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.

Posted
By ReguVirta
3 min read

What You Need to Know? 👇

What is the Dual 510(k) and CLIA Waiver by Application pathway?

It’s a streamlined FDA pathway allowing manufacturers to submit a single application for both 510(k) clearance and CLIA waiver simultaneously, reducing overall review time compared to separate sequential submissions for IVD tests.

Who should use untrained operators in dual submission studies?

Studies should use untrained operators representative of waived settings - test operators with limited or no laboratory testing experience who would actually use the device in CLIA-waived environments like physician offices.

What types of devices are most suitable for dual submissions?

Devices that are simple to use, have fail-safe and failure alert mechanisms, require few pre-analytical steps, and are subject to premarket notification requirements are especially appropriate for dual submissions.

Follow FDA-recognized consensus standards like CLSI EP21 and EP27. Include regression analysis, bias calculations at medical decision levels, and total error estimation across the entire measuring interval and subintervals.

How many sites should be included in reproducibility studies?

A minimum of 3 sites that are representative of intended waived test use, with the same number of untrained operators (likely 2 or 3) at each site to facilitate statistical analysis.

Should manufacturers contact FDA before conducting dual submission studies?

Yes, FDA strongly recommends using a Pre-Submission to discuss planned study designs for comparison and reproducibility studies that will support both 510(k) clearance and CLIA waiver before conducting studies.

What You Need to Do 👇

  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

  • Comparison studies required comparing device performance between untrained and trained operators
  • Reproducibility studies required at minimum 3 sites with untrained operators
  • Device must be demonstrated to be “simple” to use

Relevant Guidances 🔗

Related references and norms 📂

  • 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 ID: cfb7faa2eaf7748de41163b9cd08427a
FDA guidance, Final
Medical Devices Postmarket 510(k) Premarket CLIA (Clinical Laboratory Improvement Amendments)
This post is licensed under CC BY 4.0 by the author.