Endotoxin Testing for Single-Use Intraocular Ophthalmic Devices
This guidance applies to single-use intraocular ophthalmic devices used within the eye, including: - Intraocular fluids (Class III viscoelastic surgical aids) - Anterior segment solid devices like intraocular lenses, capsular tension rings, glaucoma devices - Phacofragmentation system accessories (irrigation/aspiration sleeves and tubing) The guidance specifically focuses on endotoxin testing recommendations to prevent Toxic Anterior Segment Syndrome (TASS).
Recommended Actions
- Implement endotoxin testing as part of release testing for all applicable devices
- Validate endotoxin test methods specifically for OVDs following the prescribed protocol
- Adjust extraction parameters for solid devices based on size while maintaining required sensitivity
- Review and update product labeling to ensure compliance with inflammatory claims guidance
- Consider submitting a Pre-Submission to FDA for feedback if planning animal testing for OVDs
- Ensure test methods account for device-specific characteristics (e.g., high molecular weight materials)
- Document validation of all test methods and maintain records of endotoxin testing results
- Review existing quality control procedures to prevent endotoxin contamination during manufacturing
Key Considerations
Non-clinical testing
- For OVDs: Endotoxin test method validation required with 3 lots tested in triplicate at 0.1, 0.2 and 0.5 EU/mL
- For solid devices: Extraction testing at 37-40°C with agitation for minimum 60 minutes
- Animal testing optional for OVDs to support “low inflammatory potential” claim - requires intracameral injection and 72-hour monitoring
Labelling
- OVDs should not use “non-inflammatory” claim
- “Low inflammatory potential” claim allowed only with supporting animal testing data
Biocompatibility
- Endotoxin limit for OVDs: ≤0.2 EU/mL
- Endotoxin limit for anterior segment solid devices: ≤0.2 EU/device
Safety
- Special consideration for high molecular weight OVDs may require enzyme digestion
- For cannulated/lumened devices, fluid pathway must be tested
- Standard 40mL/device extraction ratio can be adjusted for small devices
Relevant Guidances
- Immunological Testing for Medical Devices: Evaluation and Assessment of Adverse Effects
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
Related references and norms
- USP <85>: Bacterial Endotoxin Test
- ANSI/AAMI ST72: Bacterial Endotoxins - Test Methodologies, Routine Monitoring and Alternatives to Batch Testing
- ISO 15798: Ophthalmic implants - Ophthalmic viscosurgical devices
- ISO 11979-8: Ophthalmic implants - Intraocular lenses - part 8: Fundamental requirements Amendment 1
Original guidance
This post is licensed under CC BY 4.0 by the author.