Non-Clinical Testing and Labeling Requirements for Extracranial Intravascular Stents and Delivery Systems
This guidance addresses non-clinical engineering tests and labeling recommendations for self-expanding and balloon expandable extracranial intravascular stents and their associated delivery systems. It covers stents placed in coronary or peripheral arteries and saphenous vein grafts but excludes intracranial vasculature. The guidance applies to Class III devices requiring PMA approval.
What You Need to Know? 👇
What are the key non-clinical engineering tests required for intravascular stents before FDA submission?
The FDA guidance outlines comprehensive testing including material characterization, dimensional verification, mechanical properties, stress/strain analysis, fatigue testing, accelerated durability testing, particulate evaluation, MRI compatibility, and biocompatibility assessments for both stents and delivery systems.
How long should accelerated durability testing be conducted for intravascular stents?
FDA recommends testing stent durability to the equivalent of ten years of real-time use under pulsatile flow and physiologic loading. However, one year equivalent testing may be acceptable for IDE applications if supported by rigorous fatigue analysis.
What sample sizes are recommended for stent testing using the “four corners” paradigm?
The four corners paradigm tests the largest and smallest diameters at the longest and shortest lengths available. This 2x2 factorial approach ensures testing covers the extremes of the device size range to identify worst-case performance scenarios.
Are there specific MRI safety requirements for intravascular stents?
Yes, stents must be tested for MRI safety including magnetically induced deflection force, heating effects, and image artifacts. Testing should be performed at both 1.5T and 3.0T field strengths unless compelling evidence shows one represents worst-case conditions.
What biocompatibility testing is required for permanently implanted stents versus temporary delivery systems?
Permanently implanted stents require extensive testing including cytotoxicity, sensitization, systemic toxicity, hemocompatibility, genotoxicity, chronic toxicity, implantation, and carcinogenicity studies. Temporary delivery systems require fewer tests, excluding chronic toxicity, implantation, and carcinogenicity assessments.
How should particulate evaluation be conducted for coronary stents?
Particulate testing should use finished, sterilized products tracked through tortuous path fixtures mimicking worst-case anatomy. Testing must quantify particles ≥10µm, ≥25µm, and ≥50µm sizes, with ≥90% recovery validation for smaller particles and ≥75% for larger particles.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive test plan covering all required non-clinical engineering tests
- Establish test protocols with appropriate sample sizes and acceptance criteria
- Conduct material characterization including corrosion testing, especially for nitinol devices
- Perform mechanical testing including stress/strain analysis and accelerated durability testing
- Complete biocompatibility evaluation according to ISO 10993
- Conduct MRI safety and compatibility testing
- Evaluate particulate generation risk
- Validate shelf life and package integrity
- Prepare comprehensive labeling including all required sections
- Document all test results in appropriate format with raw data and statistical analysis
- Consider additional testing requirements for specific indications (bifurcation, in-stent restenosis)
- Validate sterilization process and maintain sterility during shelf life
Key Considerations
Non-clinical testing
- Material characterization including composition, shape memory properties, mechanical properties, and corrosion resistance
- Dimensional verification and functional attributes (foreshortening, recoil, integrity, radial strength, etc.)
- Stress/strain analysis and fatigue testing
- Accelerated durability testing equivalent to 10 years of use
- Particulate evaluation for risk of emboli
- Delivery system testing including dimensional verification, deployment, balloon properties, bond strength
- Shelf life testing to demonstrate package integrity and device functionality over expected lifecycle
Labelling
- Device description including materials and specifications
- Indications for use, contraindications, warnings and precautions
- MRI safety and compatibility information
- Clinical studies overview and results
- Adverse events reporting
- Patient selection and treatment guidance
- Directions for use including compliance charts
- Patient materials including implant card
Biocompatibility
- Testing based on ISO 10993 for permanent implants
- Cytotoxicity, sensitization, irritation, systemic toxicity
- Hemocompatibility testing
- Genotoxicity and carcinogenicity evaluation
- Material-mediated pyrogenicity assessment
- Nickel ion release testing for nitinol devices
Safety
- MRI safety and compatibility testing
- Radiopacity evaluation
- Crush and kink resistance testing for peripheral stents
- Additional testing for in-stent restenosis and bifurcation lesions
Other considerations
- Shelf life validation
- Package integrity testing
- Sterilization validation
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Testing and Labeling of Medical Devices for Magnetic Resonance (MR) Environment Safety and Compatibility
- Corrosion Testing and Surface Characterization Requirements for Intravascular Stents
Related references and norms 📂
- ISO 10993: Biological Evaluation of Medical Devices
- ASTM F138: Standard Specification for Wrought 18Chromium-14Nickel-2.5Molybdenum Stainless Steel Bar and Wire for Surgical Implants
- ASTM F2004: Standard Test Method for Determination of Transformation Temperature of Nickel-Titanium Alloys by Thermal Analysis
- ASTM F2079: Standard Test Method for Measuring Intrinsic Elastic Recoil of Balloon expandable Stents
- ASTM F2081: Standard Guide for Characterization and Presentation of the Dimensional Attributes of Vascular Stents
- ASTM F2129: Standard Test Method for Conducting Cyclic Potentiodynamic Polarization Measurements to Determine the Corrosion Susceptibility of Small Implant Devices
- ASTM F2394: Standard Guide for Measuring Securement of Balloon Expandable Vascular Stent Mounted on Delivery System
- ASTM F2503: Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic Resonance Environment
- IEC 60601-2-33: Medical electrical equipment – Part 2-33: Particular requirements for the safety of magnetic resonance equipment for medical diagnosis