In Vitro Diagnostic Device Studies Exempt from Investigational Device Exemption Requirements

What You Need to Know? 👇

What are the key exemptions from IDE requirements for IVD studies?

IVD studies are exempt from most IDE requirements if they use pre-amendments devices according to original labeling, substantially equivalent devices per FDA review, or meet five specific criteria: proper labeling, noninvasive nature, no significant risk invasive sampling, no energy introduction, and confirmation by established diagnostic procedures.

How do I determine if my IVD study poses significant or non-significant risk?

Significant risk IVD devices present potential for serious harm through misdiagnosis leading to life-threatening consequences or permanent impairment. Consider false positive/negative results’ impact on treatment decisions, psychological trauma, and disease spread. Non-significant risk devices don’t meet these criteria and follow abbreviated IDE requirements.

Can foreign clinical data support US IVD marketing applications?

Yes, foreign data can support US applications if applicable to US populations and medical practices, conducted by competent investigators, and validated through FDA inspection or other means. For sole support, consider population demographics, disease prevalence, laboratory practices, and medical standards differences.

What human subject protections apply to IVD studies using leftover specimens?

All IVD studies using human specimens involve human subjects and require compliance with 21 CFR Parts 50 and 56. FDA exercises enforcement discretion for informed consent regarding certain leftover specimens that are not individually identifiable, following specific guidance document requirements.

When is IRB expedited review available for IVD investigations?

IVD studies are often eligible for expedited IRB review for both initial approval and continuing review. However, expedited review cannot be used when subject identification could reasonably place subjects at risk of liability or harm to reputation, employment, or insurability.

What records and reporting requirements apply to exempt IVD studies?

Even exempt studies should maintain detailed records including raw measurements, subject co-variables, and specimen information. Electronic spreadsheets are recommended. While not subject to full IDE reporting, studies supporting FDA applications must follow Parts 50, 56, and investigator disqualification provisions.

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What You Need to Do 👇

Recommended Actions

1. Determine if study qualifies for IDE exemption under 21 CFR 812.2(c)(3)
2. If not exempt:
   • Assess risk level (significant vs non-significant)
   • Submit IDE application if significant risk
   • Follow abbreviated requirements if non-significant risk
3. Establish quality systems approach including:
   • Device accountability and traceability
   • Staff training documentation
   • Data monitoring procedures
   • Adverse event reporting system
4. Develop comprehensive protocol including:
   • Study objectives and design
   • Statistical analysis plan
   • Subject population definition
   • Specimen handling procedures
5. Implement human subject protection measures:
   • IRB review and approval
   • Informed consent process
   • Privacy protections
   • Subject safety monitoring
6. Maintain detailed records of:
   • All correspondence
   • Device receipt and disposition
   • Subject case histories
   • Protocol deviations
   • Adverse events
7. Submit required reports:
   • Progress reports (at least annually)
   • Adverse event reports
   • Final study report
   • Any FDA-requested information
8. Ensure proper labeling compliance throughout study
9. Avoid any promotion or commercialization of investigational device

Key Considerations

Clinical testing

• Studies should be performed in a representative sample of the intended use population
• Multiple testing of same subject should be avoided as it may skew performance statistics
• Clinical investigators must use medically established means of diagnosis for all subjects in exempt studies
• For studies without medically established diagnostic confirmation, IDE approval may be required

Human Factors

• All IVD studies using human specimens involve human subjects and require human subject protection
• Informed consent requirements apply unless specific exemption criteria are met
• IRB review and approval required for studies supporting FDA applications

Labelling

• Must comply with 21 CFR 809.10(c) for investigational devices
• Must include “For Investigational Use Only” statement
• Must describe performance characteristics not yet established

Safety

• Risk determination based on potential harm from misdiagnosis
• False positive/negative results must be evaluated for safety impact
• Significant risk devices require full IDE approval
• Non-significant risk devices follow abbreviated IDE requirements

Other considerations

• Quality systems approach recommended for study conduct
• Detailed records must be maintained for all study aspects
• Electronic records should comply with 21 CFR Part 11
• Promotion and commercialization of investigational devices prohibited
• Foreign data may be accepted if applicable to US population

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Relevant Guidances 🔗

• Electronic Records and Electronic Signatures - Scope and Application
• Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures
• Continuing Review of Clinical Investigations by Institutional Review Boards (IRBs)
• Quality System Information Requirements for Premarket Submissions

Related references and norms 📂

• 21 CFR Part 11: Electronic Records; Electronic Signatures
• 21 CFR Part 50: Protection of Human Subjects
• 21 CFR Part 56: Institutional Review Boards
• 21 CFR Part 809: In Vitro Diagnostic Products for Human Use
• 21 CFR Part 812: Investigational Device Exemptions
• 21 CFR Part 820: Quality System Regulation

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Original guidance

• In Vitro Diagnostic Device Studies Exempt from Investigational Device Exemption Requirements
• HTML / PDF
• Issue date: 2010-06-25
• Last changed date: 2020-02-28
• Status: FINAL
• Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Laboratory Tests, Premarket, IVDs (In Vitro Diagnostic Devices), Biologics
• ReguVirta ID: fd88e55efa0376ec23880ef6744faa84