Testing Your Device: What the FDA Looks For

1. Testing Your Device: What the FDA Looks For

2. Bio Vice President, Regulatory and Clinical Affairs • Graduated Tulane University in Biomedical Engineering; MS in Bioengineering Clemson • Develop comprehensive regulatory strategies for complex musculoskeletal devices and biologics • Review and write regulatory submissions (510(k)s, IDEs, PMAs) for orthopedic, spinal, and biological companies across the world • Design and implement mechanical, biomechanical, and animal testing and clinical study strategy and initiation for orthopedic and spinal companies • Former Branch Chief, Orthopedic Devices Branch, DSORD, CDRH • Former Spine Team Leader, DSORD, CDRH • Developed and/or reviewed over 1,000 submissions MCRA • Current Consultant to 200 Companies • Founded February 25, 2004 • 36 Employees and Independent Experts • Offices in Washington, DC  New York  Connecticut Integrated Services: US & International Regulatory, Reimbursement , Compliance, Clinical Services  Quality Assurance

3. Background 510(k) Concept • Demonstration of substantial equivalence of your device to a valid predicate • What’s a valid predicate? • A spinal system that is currently being used in the same fashion (intended use) for the same indications • Need to demonstrate equivalency in design and performance • Examples: material, mechanical characteristics, mechanism of action, sizes, sterilization, labeling • If “significant” difference, burden on company to demonstrate the risks of the differences can be mitigated. • Need to focus on stiffness, yield load, ultimate load, and failure mode • May need to have side by side testing • Have to demonstrate substantial equivalence in 2 cycles • “3 Strikes and you’re out” (original submission + 2 responses)

4. Demonstrating Mechanical Equivalence Points to Consider When developing testing protocol and plan, consider: • Case Material • Worst Case Size • Other Worst Case Considerations • Design Features • Mechanism of Action • Failure Modes • Wear Capabilities • Non-Standardized Testing • Demonstrating Substantial Equivalence

5. Materials & Sizes What the FDA Looks for Test the worst case material for each test What does that mean? • Weakest material – Polymer versus Metal • Depends on the test! • Higher stiffness but lower yield? • Higher yield due to lower stiffness? • Most devices use same material; so material selection not common Test the worst case size for each test What does that mean? • Smallest size usually worst case • Depends on the test • FDA: Tall device for torsion vs smallest footprint for compression • FEA becoming more popular: Taller devices can have more holes/visualization windows, confounds basic mechanics • Interbody Cage: Dual cages or single cage?

6. Other Considerations What the FDA Looks for • Sterilization • Device must be fully sterilized • If different sterilization processes used, which process is more-worst case? • FDA very sensitive to gamma sterilization of polymers • Laser Marking • Demonstrate laser marking does not affect performance • Size vs. Indication • AIS indications: pediatric population • Larger screws too big for anatomy • Small screws too small for skeletally mature • Coatings • HA on polymer? • Porous coating on metal? • Nitinol?

7. Design Features What the FDA Looks for • Constructs (ASTM F1717) • Standard 76mm length for pedicle screw systems • Does system include offset connector? Transverse connector? • Cages (ASTM F2077) • FEA more common to identify worst-case • Basic mechanics less reliable to predict worst-case height due to holes • Anterior Cervical Plates (ASTM F1717) • Screw back-out prevention • TDRs (ASTM F2423) • Design dependent, but smallest insert or size usually worst-case • OCT (ASTM F2706) • Plate, hooks, screws? Justify All Testing, Sizes, and Constructs

8. Mechanism of Action What the FDA Looks For • Characterize how the device works • Testing must be compared to predicate device with same indications and intended use • How does the device stabilize the spine? • Interbody • Screws • Blades • Nothing • Interspinous • Anterior/Posterior • Just because in same anatomical location, the treatment effect difference • Example: Interspinous Devices can not be compared to pedicle screws • Example: Interbody cage with screws compared to interbody cage w/no screws

9. Failure Modes What the FDA Looks For • Characterize how the device breaks/fails • Demonstrating better results not good enough • Began with Dynamic Stabilization Devices • FDA expects failure modes to be identical to predicate devices • Common failure modes • Screw breakage • Rod bending • Cage cracking • “Bone” fracture • New failure mode? • Usually due to novel design feature or material • Company must present risk assessment proactively • FDA may request clinical data

10. Wear Considerations What the FDA Looks For • When is wear data needed? • Articulating devices or mixed-material devices • Example: Cages with screws • Titanium alloy screws interfaced with PEEK cage • Wear in compression, torsion, compression-shear • TDRs • Usually softer articulating surface (e.g., PE on metal) wears • Standards dictate tested wear pattern • Metal on metal? • Must address wear specific to the tested material • Has to be same material • Limited published data to address wear safety • If no public information available, rabbit neurotoxicity study with same wear particulate needed

11. Non-standardized testing What the FDA Looks For • Purpose • Substantial Equivalence? • Safety? • Testing for a 510(k) • Non-standard testing requires predicate to be tested side-by-side • Or ability to recreate “unique” testing with reference to results • Occasionally, FDA asks for specific test to address specific issue • Bottom-line: Need for non-standardized testing = difficult SE argument • Testing for an IDE • Need to demonstrate safety • Non-standard testing more prevalent since standards don’t exist yet for newer devices (e.g., interspinous process devices) • Must justify test set-up, protocol, results based on worst-case expected, clinically relevant loading/motion

12. Demonstrating Substantial Equivalence What the FDA Looks For • FDA’s Questions: • Is there a valid predicate? • Does predicate have same indications and intended use? • How does the design compare to the predicate? • How does the device perform compared to the predicate? • Was standard method used? • If deviations, how does it affect results and comparisons • Was worst-case device tested? • Mechanical results comparison to predicate a MUST • Reviewers tend not make comparisons on their own Seek Assistance Because Setting a Bad Precedent Could Kill a Submission

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