Keratoprostheses - Special Controls and Testing Requirements for 510k Submissions
This guidance serves as a special control for the regulation of temporary and permanent keratoprostheses through 510(k) submissions. It specifically applies to devices intended for use in patients with opacified corneas, where temporary devices are used intraoperatively for visualization, and permanent devices are implanted to provide a transparent optical pathway.
What You Need to Know? 👇
What are the key biocompatibility testing requirements for keratoprostheses under FDA guidance?
Keratoprostheses must undergo cytotoxicity, genotoxicity, sensitization, intramuscular and ocular implantation tests. Chemical testing limits residual monomers to ≤1.0 wt%. Testing should use polar and nonpolar extractants on finished products.
How many subjects are required for clinical investigations of permanent keratoprostheses?
The FDA recommends a minimum of 20 subjects for clinical investigations of permanent keratoprostheses. The study design should account for potential subject loss during follow-up, with at least one year duration.
What are the dioptric power tolerance requirements for permanent keratoprostheses?
Permanent keratoprostheses must demonstrate dioptric power accuracy within ±2.0 D of the labeled power. The power must be included in the device labeling and tested on the finished marketed product.
Can temporary keratoprostheses be provided non-sterile according to FDA guidance?
Yes, temporary keratoprostheses may be provided non-sterile. However, if non-sterile, manufacturers must consult FDA’s reprocessing guidance and address pertinent reprocessing issues in their labeling and documentation.
What are the ethylene oxide residue limits for keratoprostheses sterilization?
EO residue limits are pro-rated based on device mass (using 20mg intraocular lens as reference). Ethylene chlorohydrin should not exceed 2.0 µg per device per day, maximum 5.0 µg per device.
Do temporary keratoprostheses require clinical data for 510(k) submissions?
No, clinical data are not required for temporary keratoprostheses in 510(k) submissions. Clinical investigations are only mandatory for permanent keratoprostheses, which are considered significant risk devices requiring IDE approval.
What You Need to Do 👇
Recommended Actions
- Determine device classification (temporary or permanent) and applicable requirements
- Develop comprehensive biocompatibility testing plan
- Establish and validate sterilization processes
- Design and validate packaging system
- Prepare detailed labeling according to requirements
- For permanent devices:
- Plan clinical investigation under IDE
- Develop protocol with required elements
- Establish data collection and analysis procedures
- Conduct optical performance testing
- Prepare documentation demonstrating compliance with dimensional and surface quality requirements
- Establish shelf-life validation program
- Create quality control procedures for manufacturing and testing
Key Considerations
Clinical testing
- Required for permanent keratoprostheses only
- Minimum of 20 subjects
- One-year follow-up duration
- Specific reporting periods from pre-operative to 330-420 days postoperatively
- Documentation of all adverse events and complications
Non-clinical testing
- Optical testing for dioptric power (±2.0 D tolerance for permanent devices)
- Field of view and magnification requirements for temporary devices
- Dimensions and surface quality inspection at 6X magnification
Labelling
- Manufacturer name and trade name
- Material description and device diagram
- Dioptric power (permanent) or field of view/magnification (temporary)
- Lot/batch number
- Indications for use
- Instructions for use
- Clinical results including adverse events
- Sterility information
- Single-use statement where applicable
Biocompatibility
- Cytotoxicity testing
- Genotoxicity testing
- Maximization sensitization test
- Intramuscular animal implantation test
- Ocular implantation test
- Chemical testing for residual monomers
- Extractables and hydrolytic stability testing (permanent devices only)
Safety
- Sterility validation for permanent devices
- Package integrity testing
- Shelf-life validation
- Residual limits for sterilization methods
Other considerations
- Packaging must protect device and maintain sterility
- Real-time aging preferred for shelf-life determination
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Submission Requirements for Terminally Sterilized Medical Devices
- Refuse to Accept Policy for 510k Submissions: Minimum Threshold Requirements for Administrative and Technical Review
- Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence
Related references and norms 📂
- ISO 10993-5: Biological evaluation of medical devices - Tests for cytotoxicity
- ISO 10993-3: Biological evaluation of medical devices - Tests for genotoxicity, carcinogenicity and reproductive toxicity
- ISO 10993-10: Biological evaluation of medical devices - Tests for irritation and sensitization
- ISO 11607: Packaging for terminally sterilized medical devices
- ANSI/AAMI/ISO 11134-1993: Sterilization of health care products - Requirements for validation and routine control - Industrial moist heat sterilization
- ANSI/AAMI/ISO 11135-1994: Medical devices - Validation and routine control of ethylene oxide sterilization
- ANSI/AAMI/ISO 11137: Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization