Applying Previously Cleared IVD Assays to Additional Automated Laboratory Instruments
This guidance pertains to In Vitro Diagnostic (IVD) test systems regulated by CDRH and comprised of a cleared assay that runs on an automated laboratory instrument specified by the assay manufacturer. It specifically addresses the application of a previously cleared assay to an additional instrument that was either previously cleared or is a member of an instrument family from which another member has been cleared. The guidance does not apply to: - Modifications other than application of cleared assay to additional instrument - Class III devices - Blood banking devices - Home use devices (prescription or OTC) - CLIA-waived test systems
Recommended Actions
- Confirm assay and instrument are previously cleared or part of cleared instrument family
- Assess if changes affect:
- Key components or fundamental test principles
- Instrument and software principles
- Indications for use
- Conduct risk assessment to identify new/modified risks
- Perform verification/validation testing:
- Use established protocols and acceptance criteria
- Document results and justifications
- Consider need for clinical validation
- Update labeling as needed
- Document changes and assessments in device master record
- Submit CLIA categorization request if proceeding without new 510(k)
- 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
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
Original guidance
This post is licensed under CC BY 4.0 by the author.