Retinal Prostheses: Clinical, Non-Clinical, and Safety Recommendations for Electrical Stimulation Devices

What You Need to Know? 👇

What are the key pre-clinical testing requirements for retinal prostheses before starting human trials?

Pre-clinical testing must include biocompatibility studies, animal testing for at least 6 months, electrode stimulation characterization, durability testing for minimum 5 years simulated use, electronics validation, software verification, electromagnetic compatibility assessment, and sterilization validation. All testing should follow FDA-recognized standards and Good Laboratory Practice requirements.

How long should clinical follow-up be for retinal prosthesis IDE studies?

FDA recommends following subjects for three years or longer in IDE studies. The protocol should include consent for long-term follow-up of 5-10 years post-implantation, as FDA may require continued studies as a condition of future marketing approval under 21 CFR 814.82(a)(2).

What effectiveness endpoints are recommended for retinal prosthesis clinical trials?

Primary effectiveness endpoints should include low vision letter acuity tests, grating acuity assessments, spatial mapping of phosphene fields, and form vision evaluation. Functional assessments like orientation and mobility evaluations, activities of daily living, and patient-reported outcomes using validated questionnaires are also recommended for comprehensive effectiveness demonstration.

Are retinal prostheses considered significant risk devices requiring FDA IDE approval?

Yes, FDA considers retinal prostheses significant risk devices under 21 CFR 812.3(m). Sponsors must submit an IDE application and obtain both FDA and IRB approval before beginning clinical investigations in the United States. The devices must also comply with informed consent regulations under 21 CFR Part 50.

What biocompatibility testing is required for implanted retinal prosthesis components?

All subject-contacting components require biocompatibility testing per ISO-10993 standards. This includes bacterial endotoxin testing, leachables testing in saline at 35°C for five years equivalent exposure, pyrogen testing using Rabbit Pyrogen Test, and histology evaluations. Testing should use finished devices or facsimiles with identical manufacturing processing.

What are the key labeling requirements for investigational retinal prostheses?

Labeling must include “CAUTION–Investigational device. Limited by Federal law to investigational use,” contraindications, warnings about MRI/electromagnetic compatibility, surgical procedure details, post-operative care instructions, and patient materials including user guides and implant cards. All relevant hazards, adverse effects, and precautions must be described per 21 CFR 812.5(a).

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What You Need to Do 👇

Recommended Actions

1. Develop comprehensive pre-clinical testing plan including animal studies, durability testing, and biocompatibility evaluation
2. Design clinical protocol with:
   • Clear inclusion/exclusion criteria
   • Defined safety and effectiveness endpoints
   • Statistical analysis plan
   • Long-term follow-up strategy
3. Create detailed device description documentation including:
   • Engineering drawings
   • Material specifications
   • Software documentation
   • Manufacturing process description
4. Establish risk management process and documentation
5. Develop complete labeling package including:
   • Surgical procedure
   • Warnings and precautions
   • Patient information
   • Training materials
6. Create sterilization validation protocol
7. Prepare IDE submission package with all required elements
8. Consider requesting Pre-Submission meeting with FDA to discuss study design and requirements

Key Considerations

Clinical testing

• Follow subjects for minimum 3 years
• Evaluate visual performance at intervals of max 3 months for first year, max 6 months thereafter
• Include assessments of:
  • Visual function (acuity, grating, spatial mapping)
  • Functional vision in real-world situations
  • Patient reported outcomes
• Use independent professionals for orientation/mobility assessments
• Include statistical analysis plan with sample size justification

Non-clinical testing

• Conduct animal testing on active finished device before human trials
• Perform acute tests (24h) and long-term tests (6+ months) in animal models
• Evaluate histology and device functionality post-explantation
• Conduct accelerated lifetime tests for durability
• Validate welding/bonding processes
• Test flexion under simulated use conditions

Human Factors

• Evaluate usability of portable controller
• Assess tactile controls and indicators
• Consider impact resistance and water resistance
• Ensure ease of battery replacement
• Validate all patient and clinician software

Software

• Describe physician fitting software and patient controls
• Include fail-safes and protection against programming errors
• Validate software according to level of concern
• Include resets/presets and device feedback mechanisms

Labelling

• Include contraindications, warnings, precautions
• Describe surgical procedure in detail
• Provide patient information and implant card
• Include electromagnetic compatibility warnings
• Detail storage conditions and battery information

Biocompatibility

• Provide material biocompatibility profiles
• Conduct bacterial endotoxin testing
• Perform leachables testing
• Conduct pyrogen testing
• Test material stability in saline environment

Safety

• Identify primary safety endpoint
• Track surgical complications and adverse events
• Define acceptable risk levels
• Report unanticipated adverse effects within 10 days
• Monitor device hermeticity

Other considerations

• Sterilize implanted components to SAL 10-6
• Validate sterilization processes
• Test package integrity
• Consider MRI compatibility
• Evaluate electromagnetic interference

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Relevant Guidances 🔗

• Spinal Plating Systems and Vertebral Body Replacement Devices - Content and Testing Requirements for 510k Submissions
• Design Controls for Medical Device Manufacturers
• Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
• Content of Premarket Submissions for Device Software Functions
• Applying Human Factors Engineering and Usability Engineering to Medical Devices
• Benefit-Risk Determinations for Medical Device Premarket Review

Related references and norms 📂

• ISO 15004-1:2006: Ophthalmic instruments - Fundamental requirements and test methods
• IEC 60601-1-2:2001: Medical Electrical Equipment - Electromagnetic compatibility
• ISO 10993-7: Biological Evaluation of Medical Devices - Ethylene Oxide Sterilization Residuals
• ISO 17665-1:2006: Sterilization of health care products - Moist heat
• ISO 11135-1:2007: Sterilization of health care products - Ethylene oxide
• ISO 11607-1/2:2006: Packaging for terminally sterilized medical devices
• ASTM F1980-07: Standard Guide for Accelerated Aging of Sterile Barrier Systems

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Original guidance

• Retinal Prostheses: Clinical, Non-Clinical, and Safety Recommendations for Electrical Stimulation Devices
• HTML / PDF
• Issue date: 2013-03-06
• Last changed date: 2020-02-28
• Status: FINAL
• Official FDA topics: Medical Devices, Ophthalmic, Investigational Device Exemption (IDE)
• ReguVirta ID: e13dd67789cd29e513af7961e968e722