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CLIA Waiver Applications for In Vitro Diagnostic Devices - Demonstrating Simplicity and Insignificant Risk of Erroneous Results

This guidance provides recommendations for device manufacturers seeking CLIA waiver applications to demonstrate that their in vitro diagnostic devices meet the statutory criteria of being simple and having an insignificant risk of an erroneous result. It covers requirements for demonstrating simplicity, risk analysis, validation studies, and labeling requirements.

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By ReguVirta
3 min read

What You Need to Know? 👇

What are the key requirements for obtaining CLIA waiver for an in vitro diagnostic device?

A device must be “simple” and have “insignificant risk of erroneous result.” This includes being fully automated or unitized, using direct unprocessed specimens, requiring minimal operator intervention, and having fail-safe mechanisms or failure alerts to prevent errors.

How do I demonstrate that my device is “simple” under CLIA waiver criteria?

Your device should be fully automated or self-contained, use direct specimens like fingerstick blood or urine, need no technique-dependent manipulation, require no operator intervention during analysis, and include instructions written at 7th grade reading level or lower.

What study design options are available to demonstrate accuracy for CLIA waiver applications?

Four options exist: comparing untrained vs trained operators with your device, using assay migration study approaches, conducting flex and human factors studies, or directly comparing untrained operators using your device against trained operators using comparative methods.

What are fail-safe mechanisms and failure alert mechanisms in CLIA waiver applications?

Fail-safe mechanisms prevent result output when conditions are inappropriate (e.g., lock-out functions for expired reagents). Failure alert mechanisms notify operators of malfunctions or problems (e.g., “out of range” messages, external controls, internal procedural controls).

How many operators and testing sites are required for CLIA waiver studies?

Studies should include minimum three representative testing sites with 1-3 untrained operators per site (at least 9 total untrained operators). Sites should represent intended use settings like physician offices or outpatient clinics across different demographics.

What labeling requirements apply specifically to CLIA waived devices?

Labeling must include a Quick Reference Guide written at 7th grade level, package insert identifying the test as CLIA waived, step-by-step instructions with pictures, quality control procedures, and manufacturer contact information for technical assistance.

What You Need to Do 👇

  1. Conduct comprehensive risk analysis to identify all potential sources of error
  2. Design and implement appropriate fail-safe and failure alert mechanisms
  3. Develop simple instructions written at 7th grade reading level
  4. Perform flex studies under stress conditions
  5. Validate all control measures and fail-safe mechanisms
  6. Conduct clinical studies at minimum 3 sites with at least 9 untrained operators
  7. Create Quick Reference Guide with clear instructions and pictures
  8. Establish quality control procedures and recommendations
  9. Prepare comprehensive labeling including all required elements
  10. Set up technical support system for users
  11. Implement medical device reporting procedures
  12. Consider submitting Pre-Submission to FDA for feedback before conducting studies

Key Considerations

Clinical testing

  • Minimum of 3 testing sites representative of intended use settings
  • At least 9 untrained operators across all sites
  • Testing should be integrated into daily workflow
  • Prospective patient specimens preferred, with option to supplement with archived/surrogate samples
  • Split samples required for comparison testing

Non-clinical testing

  • Flex studies required to challenge system under stress conditions
  • Validation studies needed for fail-safe and failure alert mechanisms
  • Risk analysis and control measures validation required

Human Factors

  • Untrained operators should have limited/no laboratory testing experience
  • No additional training beyond provided instructions allowed during studies
  • Operator questionnaire required after study completion
  • Instructions must be written at 7th grade reading level or lower

Software

  • Software should incorporate data retention and error detection capabilities
  • Lock-out functions required for expired reagents, failed controls, etc.
  • Electronic system checks required

Labeling

  • Quick Reference Guide required with simple instructions and pictures
  • Package insert must include CLIA waiver information
  • Quality control procedures must be clearly explained
  • Educational materials recommended
  • MedWatch reporting information required

Safety

  • Universal precautions compliance required
  • Safety considerations for untrained users must be included in labeling
  • Physical features required to prevent improper device use

Other considerations

  • Quality control materials and procedures required
  • External controls recommended when feasible
  • Device maintenance requirements must be simple
  • Technical support contact information required

Relevant Guidances đź”—

Related references and norms đź“‚

  • ISO 14971: Medical devices - Application of risk management to medical devices

Original guidance

  • CLIA Waiver Applications for In Vitro Diagnostic Devices - Demonstrating Simplicity and Insignificant Risk of Erroneous Results
  • HTML / PDF
  • Issue date: 2020-02-26
  • Last changed date: 2024-08-09
  • Status: FINAL
  • Official FDA topics: Medical Devices, CLIA (Clinical Laboratory Improvement Amendments), Biologics
  • ReguVirta ID: 223892ded6afa235feb621f7de040016
FDA guidance, Final
Medical Devices CLIA (Clinical Laboratory Improvement Amendments) Biologics
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