2Bio Vice President, Regulatory and Clinical Affairs MCRA Graduated Tulane University in Biomedical Engineering; MS in Bioengineering ClemsonDevelop comprehensive regulatory strategies for complex musculoskeletal devices and biologicsReview and write regulatory submissions (510(k)s, IDEs, PMAs) for orthopedic, spinal, and biological companies across the worldDesign and implement mechanical, biomechanical, and animal testing and clinical study strategy and initiation for orthopedic and spinal companiesFormer Branch Chief, Orthopedic Devices Branch, DSORD, CDRHFormer Spine Team Leader, DSORD, CDRHDeveloped and/or reviewed over 1,000 submissionsMCRACurrent Consultant to 200 CompaniesFounded February 25, 200436 Employees and Independent ExpertsOffices in Washington, DC New York ConnecticutMy name is Rosco Barthalemew Glennius Quissenart StiegmanIntegrated Services: US & International Regulatory, Reimbursement , Compliance, Clinical Services Quality Assurance
3Background 510(k) Concept Demonstration of substantial equivalence of your device to a valid predicateWhat’s a valid predicate?A spinal system that is currently being used in the same fashion (intended use) for the same indicationsNeed to demonstrate equivalency in design and performanceExamples: material, mechanical characteristics, mechanism of action, sizes, sterilization, labelingIf “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 modeMay need to have side by side testingHave to demonstrate substantial equivalence in 2 cycles“3 Strikes and you’re out” (original submission + 2 responses)
4Demonstrating Mechanical Equivalence Points to ConsiderWhen developing testing protocol and plan, consider:Case MaterialWorst Case SizeOther Worst Case ConsiderationsDesign FeaturesMechanism of ActionFailure ModesWear CapabilitiesNon-Standardized TestingDemonstrating Substantial Equivalence
5Materials & Sizes What the FDA Looks for Test the worst case material for each testWhat does that mean?Weakest material – Polymer versus MetalDepends on the test!Higher stiffness but lower yield?Higher yield due to lower stiffness?Most devices use same material; so material selection not commonTest the worst case size for each testSmallest size usually worst caseDepends on the testFDA: Tall device for torsion vs smallest footprint for compressionFEA becoming more popular: Taller devices can have more holes/visualization windows, confounds basic mechanicsInterbody Cage: Dual cages or single cage?
6Other Considerations What the FDA Looks for Sterilization Device must be fully sterilizedIf different sterilization processes used, which process is more-worst case?FDA very sensitive to gamma sterilization of polymersLaser MarkingDemonstrate laser marking does not affect performanceSize vs. IndicationAIS indications: pediatric populationLarger screws too big for anatomySmall screws too small for skeletally matureCoatingsHA on polymer?Porous coating on metal?Nitinol?
7Justify All Testing, Sizes, and Constructs Design FeaturesWhat the FDA Looks forConstructs (ASTM F1717)Standard 76mm length for pedicle screw systemsDoes system include offset connector? Transverse connector?Cages (ASTM F2077)FEA more common to identify worst-caseBasic mechanics less reliable to predict worst-case height due to holesAnterior Cervical Plates (ASTM F1717)Screw back-out preventionTDRs (ASTM F2423)Design dependent, but smallest insert or size usually worst-caseOCT (ASTM F2706)Plate, hooks, screws?Justify All Testing, Sizes, and Constructs
8Characterize how the device works Mechanism of ActionWhat the FDA Looks ForCharacterize how the device worksTesting must be compared to predicate device with same indications and intended useHow does the device stabilize the spine?InterbodyScrewsBladesNothingInterspinousAnterior/PosteriorJust because in same anatomical location, the treatment effect differenceExample: Interspinous Devices can not be compared to pedicle screwsExample: Interbody cage with screws compared to interbody cage w/no screws
9Characterize how the device breaks/fails Failure ModesWhat the FDA Looks ForCharacterize how the device breaks/failsDemonstrating better results not good enoughBegan with Dynamic Stabilization DevicesFDA expects failure modes to be identical to predicate devicesCommon failure modesScrew breakageRod bendingCage cracking“Bone” fractureNew failure mode?Usually due to novel design feature or materialCompany must present risk assessment proactivelyFDA may request clinical data
10When is wear data needed? Wear ConsiderationsWhat the FDA Looks ForWhen is wear data needed?Articulating devices or mixed-material devicesExample: Cages with screwsTitanium alloy screws interfaced with PEEK cageWear in compression, torsion, compression-shearTDRsUsually softer articulating surface (e.g., PE on metal) wearsStandards dictate tested wear patternMetal on metal?Must address wear specific to the tested materialHas to be same materialLimited published data to address wear safetyIf no public information available, rabbit neurotoxicity study with same wear particulate needed
11Non-standardized testing What the FDA Looks ForPurposeSubstantial Equivalence?Safety?Testing for a 510(k)Non-standard testing requires predicate to be tested side-by-sideOr ability to recreate “unique” testing with reference to resultsOccasionally, FDA asks for specific test to address specific issueBottom-line: Need for non-standardized testing = difficult SE argumentTesting for an IDENeed to demonstrate safetyNon-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
12Demonstrating Substantial Equivalence What the FDA Looks ForFDA’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 comparisonsWas worst-case device tested?Mechanical results comparison to predicate a MUSTReviewers tend not make comparisons on their ownSeek Assistance Because Setting a Bad Precedent Could Kill a Submission