Coronary and Carotid Embolic Protection Devices - Performance Testing and Labeling Requirements
This guidance addresses coronary and carotid embolic protection devices designed to capture and remove embolic material during interventional treatment of carotid arteries or saphenous vein bypass grafts. It covers devices used along with other interventional devices for: - Treatment of diseased saphenous vein grafts in patients with stable ischemic coronary artery disease - Treatment of diseased carotid arteries that could potentially contribute to strokes or neurological adverse events
What You Need to Know? 👇
What are the key biocompatibility testing requirements for embolic protection devices?
FDA recommends biocompatibility testing per ISO-10993 for external devices contacting circulating blood for limited duration (<24 hours). Testing should include cytotoxicity, sensitization, hemocompatibility (hemolysis, complement activation, thromboresistance), material-mediated pyrogenicity, and endotoxin testing using both polar and nonpolar extractants.
Can I submit an Abbreviated 510(k) for coronary and carotid embolic protection devices?
Yes, FDA recommends Abbreviated 510(k) submissions as the least burdensome approach. The submission must include required elements per 21 CFR 807.87, proposed labeling, and a summary report describing how you used this guidance during device development and testing.
What animal testing is required for embolic protection devices before clinical trials?
FDA recommends GLP or GLP-like animal studies using appropriate models (swine carotid arteries for SVG devices, tortuous subclavian vessels for carotid devices). Studies should include acute (24-72 hours) and chronic (1 month) assessments with pathology evaluations and embolic capture testing using thrombosis models.
Are clinical studies always required for 510(k) clearance of embolic protection devices?
Generally yes, because bench and animal testing alone are typically inadequate due to limitations in flow modeling, lack of ideal animal models for diseased vessels, and absence of proven embolic material models. However, clinical data may not be needed for minor design changes with appropriate scientific rationale.
What are the recommended primary endpoints for coronary embolic protection device studies?
FDA recommends major adverse cardiac events (MACE) at 30 days as the primary endpoint, including cardiac deaths, myocardial infarctions (Q-wave and non-Q-wave), target vessel revascularization, and emergency coronary artery bypass grafting. Post-procedure CK or CK-MB levels are essential for detecting non-Q-wave MI.
What sterilization requirements apply to embolic protection devices?
Devices must be sterilized to sterility assurance level (SAL) of 1 x 10⁻⁶ using validated sterilization cycles per 21 CFR Part 820. Since these devices contact circulating blood, pyrogenicity testing is required using methods like LAL testing, with shelf life testing addressing package integrity and device functionality.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive bench testing plan covering all required performance characteristics
- Plan and execute animal studies following GLP requirements with both acute and chronic timepoints
- Design clinical study with appropriate endpoints and follow-up requirements
- Implement biocompatibility testing program per ISO 10993-1
- Validate sterilization process and establish shelf life
- Develop comprehensive labeling including all required warnings, contraindications and instructions
- Consider early engagement with FDA through Pre-IDE process, especially for novel technologies
- Establish quality system controls for design, manufacturing and testing
- Prepare documentation demonstrating compliance with all applicable standards
- Develop training program for healthcare practitioners
Key Considerations
Clinical testing
- Primary endpoint of major adverse cardiac events (MACE) at 30 days for coronary devices
- Primary endpoint of major adverse cardiac and cerebrovascular events at 30 days for carotid devices
- Independent Clinical Events Committee and Data Monitoring Committee recommended
- Core laboratory recommended for data analysis
- Office visits required for follow-up (no telephone follow-up)
Non-clinical testing
- Animal studies required with acute (24-72h) and chronic (1 month) timepoints
- Animal model should mimic target anatomy
- Study protocol should simulate clinical procedure
- Assess vascular injury, inflammation, and neointimal response
- Evaluate hemolysis potential
- Assess device removal with full embolic load
Software
- Software validation required if device contains software
- Follow FDA guidance for software in medical devices
Labelling
- Clear instructions for use by healthcare practitioners
- Description of device failure modes and mitigations
- List of contraindications
- Specific warnings and precautions
- Summary of clinical study results
- Training program recommendations
Biocompatibility
- Testing per ISO 10993-1 for blood-contacting devices
- Cytotoxicity testing
- Sensitization testing
- Hemocompatibility testing
- Material-mediated and endotoxin-mediated pyrogenicity testing
Safety
- Sterilization validation to SAL 10-6
- Shelf life testing for package integrity and device functionality
- Pyrogenicity testing required
Other considerations
- Bench testing required for:
- Embolic capture efficiency
- Stent compatibility
- Flow characteristics
- Radial force
- Tensile and torque strength
- Dimensional verification
- Coating integrity
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Content of Premarket Submissions for Device Software Functions
- Software Validation for Medical Device Production, Quality Systems, and Device Components
Related references and norms 📂
- ISO 10993-1: Biological Evaluation of Medical Devices - Evaluation and Testing
- ISO 10993-12: Biological Evaluation of Medical Devices - Sample Preparation and Reference Materials
- ASTM F2065: Standard Practice for Testing for Alternative Pathway Complement Activation in Serum by Solid Materials
- ASTM F1984: Standard Practice for Testing for Whole Complement Activation in Serum by Solid Materials
- EN 60601-1: General Requirements for Safety
- EN 60601-1-1: Safety Requirements for Medical Electrical Systems
- EN 60601-1-2: Electromagnetic Compatibility – Requirements and Tests