Applying Previously Cleared IVD Assays to Additional Automated Laboratory Instruments

What You Need to Know? 👇

What is the Replacement Reagent Policy for IVD devices?

The Replacement Reagent Policy allows manufacturers to apply a previously cleared assay to additional cleared instruments without submitting a new 510(k), provided specific conditions are met including risk assessment, validation testing, and documentation requirements.

When does the Instrument Family Policy apply to IVD modifications?

The Instrument Family Policy applies when modifying an instrument to create a new family member with the same general architecture, design, tolerance limits, and capabilities, sharing common hardware/software components related to test reaction and interpretation.

What documentation is required when applying these policies without a 510(k)?

Manufacturers must document design/production changes in the device master record, conduct risk-based assessments, perform validation testing with pre-specified acceptance criteria, and maintain detailed protocols and results per 21 CFR 820 requirements.

Are there specific IVD device types excluded from these policies?

Yes, exclusions include Class III devices, blood banking devices, prescription/OTC home use devices, CLIA-waived test systems, and devices with specific FDA guidance stating these policies don’t apply, though this guidance modifies some previous exclusions.

What testing is typically required for replacement reagent validation?

Common testing includes CLSI guideline-based studies for precision (EP-05), linearity (EP-06), method comparison (EP-09), interference (EP-07), carry-over studies, matrix equivalence (EP-35), and on-board stability testing, based on risk assessment.

How does CLIA categorization work for devices using these policies?

Manufacturers must submit CLIA categorization requests including signed cover pages, instrument/assay specifications with 510(k) numbers, package inserts, and operator manuals. FDA assigns CR numbers and categorizes within 30 days without substantial equivalence determination.

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What You Need to Do 👇

Recommended Actions

1. Confirm assay and instrument are previously cleared or part of cleared instrument family
2. Assess if changes affect:
   • Key components or fundamental test principles
   • Instrument and software principles
   • Indications for use
3. Conduct risk assessment to identify new/modified risks
4. Perform verification/validation testing:
   • Use established protocols and acceptance criteria
   • Document results and justifications
   • Consider need for clinical validation
5. Update labeling as needed
6. Document changes and assessments in device master record
7. Submit CLIA categorization request if proceeding without new 510(k)
8. Consider consulting FDA if unclear about applicability to specific technology

Key Considerations

Clinical testing

• Clinical validation may be needed in some cases when analytical validation alone is not adequate
• If clinical study is necessary, a new 510(k) is likely required

Non-clinical testing

• Verification and validation testing should be based on manufacturer’s quality processes and risk assessment
• Testing protocols should be sufficiently robust to identify significant performance changes
• Acceptance criteria should be clinically justified
• Sample sizes should be statistically justified if different from original 510(k)

Software

• Software modifications for system integration, signal processing, data acquisition or interpretation likely require new 510(k)
• Software validation required per FDA guidance

Labeling

• Must comply with 21 CFR parts 801 and 809
• Package inserts must include procedural steps for new instrument
• Application sheets should be referenced in package insert
• Clearly state which instruments were tested
• Update operator manuals with new specifications

Other considerations

• Risk assessment required to identify new or modified risks
• Document changes and approvals in device master record
• Submit CLIA categorization request for database update
• Instrument family members must share same architecture, design, tolerances and capabilities

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Relevant Guidances 🔗

• Research Use Only and Investigational Use Only In Vitro Diagnostic Products - Labeling and Distribution Requirements
• In Vitro Diagnostic Device Studies Exempt from Investigational Device Exemption Requirements
• Administrative Procedures for CLIA Categorization of In Vitro Diagnostic Tests
• CLIA Waiver Applications for In Vitro Diagnostic Devices - Demonstrating Simplicity and Insignificant Risk of Erroneous Results
• Dual 510k and CLIA Waiver by Application for In Vitro Diagnostic Tests

Related references and norms 📂

• CLSI EP-17: Detection capability
• CLSI EP-05: Precision evaluation
• CLSI EP-06: Linearity evaluation
• CLSI EP-07: Interference testing
• CLSI EP-09: Method comparison
• CLSI EP-35: Matrix equivalence studies

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Original guidance

• Applying Previously Cleared IVD Assays to Additional Automated Laboratory Instruments
• HTML / PDF
• Issue date: 2022-08-17
• Last changed date: 2022-08-16
• Status: FINAL
• Official FDA topics: Medical Devices, Laboratory Tests
• ReguVirta ID: 5aa6f0ed4878ede86b14156ff9b30cbb