Migration Studies for In Vitro Diagnostic Devices Moving to New Systems
This guidance outlines FDA's regulatory approach for approval of Class III in vitro diagnostic devices, as well as certain licensed or cleared in vitro diagnostic devices when migrating (transitioning) to another system for which assay performance has not been evaluated by FDA. It focuses on study designs and performance criteria for analytical and comparison studies to demonstrate that the safety and effectiveness of the assay is not compromised when moving to the new system.
What You Need to Know? 👇
What is the purpose of assay migration studies for IVD devices?
Assay migration studies provide a least burdensome regulatory pathway for transferring previously approved/licensed assays from an old system to a new system without requiring full clinical studies, while ensuring safety and effectiveness are maintained.
When should the migration studies paradigm NOT be applied?
Migration studies should not be used for over-the-counter devices, prescription home use systems, devices with significant system changes, or when scientific evidence suggests migration studies cannot predict actual clinical performance.
What are the key acceptance criteria for qualitative assay migration studies?
Systematic differences between systems must be clinically insignificant, precision ratios should be acceptable, and positive/negative percent agreements must have lower 95% confidence intervals above 90% with discordant results only near cutoffs.
How many samples are required for quantitative assay comparison panels?
At least 180 samples are required, with 150 spanning the measuring range (equal distribution across low/medium/high concentrations) and 30 samples at or near zero concentration if clinically important.
What special considerations apply to molecular assays in migration studies?
Molecular assays require additional studies including viremic profile panels, mandatory carryover studies due to amplification risks, sample stability evaluation for DNA/RNA, and validation of control materials and calibrators.
What documentation must accompany migration study submissions?
Submissions must include device descriptions, similarities/differences tables, risk analyses, software validation summaries, system operator manuals, proposed labeling modifications, and appropriate Quality Systems documentation for new instruments.
What You Need to Do 👇
Recommended Actions
- Determine if assay migration studies approach is appropriate based on critical considerations
- Prepare and submit documentation including:
- Device descriptions and block diagrams comparing old and new systems
- Similarities/differences tables for assay parameters and hardware/software
- Risk analysis of new system
- Software validation data
- System operator manuals
- Proposed labeling modifications
- Conduct required analytical studies:
- Performance at low analyte levels
- Within-laboratory precision studies
- Multi-site reproducibility studies
- Comparison studies using appropriate panels
- Additional studies specific to assay type (qualitative/quantitative/molecular)
- Perform statistical analysis to demonstrate:
- No clinically significant systematic differences between systems
- Comparable precision between systems
- Acceptable agreement in comparison studies
- Investigate and assess risk of any significant differences found between systems
- Consult with FDA early in process, especially for manual to automated system migrations
Key Considerations
Non-clinical testing
- Analytical studies including performance at low analyte levels, precision studies (within-laboratory and reproducibility)
- Comparison studies between old and new systems using comparison panels
- Statistical analysis of data to demonstrate equivalence between systems
- For quantitative assays: linearity studies
- For molecular assays: additional specific testing for carryover, sample stability, sample processing
Software
- Documentation of software design controls, verification and validation
- Summaries validating functional operation of alerts and alarms
- Testing should use final release candidate software
Labelling
- Proposed modifications to labeling to appropriately describe prior data and new migration study information
- Consultation with FDA on dual or separate package inserts
- Inclusion of old system’s analytical and performance data where appropriate
Safety
- Risk analysis of the new system (software/hardware/assay)
- Documentation of design controls and quality systems
Other considerations
- Intended use and indications must remain unchanged except for inclusion of new system
- Reagent and assay parameters should be unchanged except for minor optimizations
- Assay and system technologies should remain unchanged
- No expected change to assay performance on new system
Relevant Guidances 🔗
- Software Validation for Medical Device Production, Quality Systems, and Device Components
- Content of Premarket Submissions for Device Software Functions
- Off-The-Shelf Software in Medical Devices: Documentation Requirements for Premarket Submissions
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
Related references and norms 📂
- ISO 14971:2007: Medical devices – Application of risk management to medical devices
- CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
- CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures
- CLSI EP09-A2-IR: Method Comparison and Bias Estimation Using Patient Samples
- CLSI EP12-A2: User Protocol for Evaluation of Qualitative Test Performance
- CLSI EP15-A2: User Verification of Performance for Precision and Trueness
- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
- CLSI EP21-A: Estimation of Total Analytical Error for Clinical Laboratory Methods