Total Artificial Disc Devices - Pre-clinical Testing and Clinical Trial Design Requirements

What You Need to Know? 👇

What are the key preclinical testing requirements for total artificial disc IDE submissions?

FDA recommends comprehensive mechanical testing including static/dynamic characterization, durability/wear testing, subluxation/expulsion assessment, and animal studies. Testing should use final sterilized components and demonstrate device performance under physiological conditions for 10 million cycles.

How should clinical endpoints be defined for total artificial disc studies?

Primary endpoints should include pain assessment and activities of daily living function. Secondary endpoints must evaluate device migration, failure, fusion absence, motion preservation, neurologic status, and disc height maintenance. Success criteria should account for placebo effects.

What animal testing is required for artificial disc devices before human trials?

FDA recommends functional animal studies using appropriate models (sheep, goats, primates) and particulate studies in small animals to evaluate biocompatibility and tissue response to wear debris. Studies should include 3 and 6-month timepoints with comprehensive histological analysis.

What are the inclusion and exclusion criteria recommendations for artificial disc studies?

Include patients with degenerative disc disease and adequate bone density. Exclude patients with <5mm disc space, severe spondylolisthesis (>Grade I), myelopathy, spinal stenosis, or conditions requiring posterior element removal that could cause instability.

How long should clinical follow-up be for total artificial disc studies?

FDA recommends minimum 2-year follow-up for primary endpoints, with provisions for 5-10 year post-approval studies. Protocols should include patient consent for long-term follow-up and sufficient enrollment to maintain statistical power despite expected attrition.

What special considerations apply to metal-on-metal artificial disc devices?

All metal-on-metal articulating devices must include serum metal ion level analyses to evaluate potential risks of tumor formation and carcinogenesis. Protocols should address metal ion release safety concerns similar to those identified in hip implants.

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What You Need to Do 👇

Recommended Actions

1. Develop comprehensive pre-clinical testing plan addressing mechanical, wear, and biocompatibility requirements
2. Design clinical study protocol with minimum 2-year follow-up
3. Establish clear success criteria for both individual subjects and overall study
4. Prepare detailed surgical technique manual and labeling
5. Implement retrieval analysis program
6. Develop monitoring and data collection procedures
7. Create comprehensive risk analysis documentation
8. Plan for potential long-term post-approval studies
9. Establish metal ion level monitoring for metal-on-metal devices
10. Prepare detailed Case Report Forms capturing all required data points

Key Considerations

Clinical testing

• Multi-center, randomized, prospective, concurrently controlled clinical trial recommended
• Minimum 2 years follow-up data required
• Study endpoints should include pain, function, neurological status, and radiographic assessments
• Subject success criteria must account for placebo effect
• Metal ion level analyses required for metal-on-metal devices

Non-clinical testing

• Static and dynamic mechanical characterization testing
• Durability and wear testing with particle analysis
• Subluxation and expulsion risk assessment
• Creep and stress relaxation testing for viscoelastic materials
• Subsidence risk evaluation
• Device migration assessment
• Coating durability testing if applicable

Labelling

• Must include intended uses, device description, contraindications, precautions, warnings
• Surgical technique manual required with explantation and revision procedures
• Instructions affecting safety should be highlighted
• Informed consent documents required with specific risk disclosures

Biocompatibility

• Testing according to ISO 10993-1
• Additional animal studies may be needed for novel materials
• Polymer characterization required if applicable
• Extraction analysis required for materials with potential leachables

Safety

• Comprehensive risk analysis required
• Retrieval study plan recommended
• Adverse event monitoring and reporting procedures
• Safety endpoints include device migration, neurological status, complications

Other considerations

• Statistical analysis plan required
• Monitoring procedures must be defined
• Case Report Forms must capture all protocol requirements
• Shelf life evaluation for applicable devices

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Relevant Guidances 🔗

• Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
• Design Controls for Medical Device Manufacturers
• Testing of Non-Articulating, Mechanically Locked Modular Implant Components in Orthopedic Devices
• Testing Requirements for Orthopedic Implants with Modified Metallic Bone-Interface Surfaces
• Medical Device Reporting (MDR) Requirements and Procedures for Manufacturers

Related references and norms 📂

• ASTM F2345-05: Standard Test Methods for Static and Dynamic Characterization of Spinal Artificial Discs
• ASTM F2423: Standard Guide for Functional, Kinematic, and Wear Assessment of Total Disc Prostheses
• ASTM F561: Standard Practice for Retrieval and Analysis of Medical Devices
• ASTM F1877: Standard Practice for Characterization of Particles
• ISO 10993-1: Biological evaluation of medical devices

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Original guidance

• Total Artificial Disc Devices - Pre-clinical Testing and Clinical Trial Design Requirements
• HTML / PDF
• Issue date: 2008-04-11
• Last changed date: 2020-03-20
• Status: FINAL
• Official FDA topics: Medical Devices, Investigational Device Exemption (IDE), Orthopedic, Premarket
• ReguVirta ID: f5d2abe5941132e7246f9adf3ee60128