Testing Your Device: What the FDA Looks

For

ConfidentialConfidential

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

BIO

Integrated Services: US & International Regulatory, Reimbursement , Compliance, Clinical Services Quality Assurance

• 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)

Background510(k) Concept

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

Demonstrating Mechanical EquivalencePoints to Consider

Test the worst case material for each testWhat 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 testWhat 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?

Materials & SizesWhat the FDA Looks for

Other Considerations

• 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?

What the FDA Looks for

Design Features

• 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?

What the FDA Looks for

Justify All Testing, Sizes, and Constructs

Mechanism of ActionWhat 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

Failure ModesWhat 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

Wear ConsiderationsWhat 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

Non-standardized testingWhat 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

Demonstrating Substantial EquivalenceWhat 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

Thank you