1. Currently, the FDA Guidance for Spinal Implant 510(k) s, which extensively 
    covers devices intended for fusion, recommends various static and fatigue 
    testing for spinal devices. Because devices not intended for fusion are intended 
    to stabilize the spinal motion segment and retain functional motion, they 
    must be designed to last for the lifetime of the individual rather than until 
    a fusion occurs. Therefore, the current testing requested for devices intended 
    for fusion and non-fusion may not be adequate. The FDA currently requests 
    the following testing for spinal devices: 
  
 
    
Fusion devices (devices intended to stabilize by fusing 
      motion segments, e.g., pedicle screw systems, intervertebral fusion devices, 
      vertebral body fusion devices, etc.)
  
  

    
Fatique - The fatigue testing should involve a minimum 
      of six samples of the worst case construct to generate a stress (load) versus 
      number of cycles (S/N) curve that characterizes the asymptotic endurance 
      limit (e.g., a minimum of two samples per load level with one load level 
      reaching a run out value of five million cycles) compared 
      to a appropriate control device. Rationale for the components chosen as 
      worst case should be provided. The interconnection mechanisms/systems may 
      be tested in the same set of constructs or each in a separate set of constructs. 
      Each interconnection mechanism should be tested or an adequate rationale 
      for not testing an interconnection should be provided. Additionally, testing 
      should be performed out to a minimum run out of 10 million cycles for intervertebral 
      body replacement devices intended for tumor patients because these patients 
      may present a great difficulty in achieving fusion, and, therefore, the 
      device is acting more as a stabilizer.

    
    
Static - The testing should involve a minimum of five 
      samples of the worst case construct. As with the fatigue testing, the components 
      tested and the loading mode should be justified.

      

      Examples of the types of construct testing typically performed for a given 
      type of spinal system in order to establish relative safety are as follows: 
      

    
    
For lumbar and thoracic pedicle screw systems that are intended for fusion, 
      static and fatigue bending testing should be provided (e.g., ASTM F1717).

    
    
For cervical, pedicle or lateral mass systems intended for fusion, static 
      and fatigue testing should be provided. The loading mode (torsional or bending) 
      is dependent on the design and material.

    
    
For intervertebral body fusion devices, static, fatigue, and expulsion 
      (push-out testing) testing should be provided. The loading mode (axial, 
      torsional, bending, and/or shear) is dependent on the design, material, 
      and levels of use.

    
    
For vertebral body replacement devices, static and fatigue testing in 
      bending and torsional loading modes should be provided. 
      
Non-Fusion devices (devices intended to stabilize yet 
        retain functional motion, e.g., disc nucleus replacements, intervertebral 
        disc prosthesis, screw or hook based stabilization spinal systems without 
        attempting fusion)
    
  
  
 
    
These are the current recommendations by the FDA for testing of these types 
      of devices.
  
  

    
Compression Fatigue - The fatigue testing should involve 
      a minimum of six samples of the worst case construct to generate a stress 
      (load) versus number of cycles (S/N) curve that characterizes the asymptotic 
      endurance limit (e.g., a minimum of two samples per load level with one 
      load level reaching a run out value of ten million cycles) compared to a 
      appropriate control device. Rationale for the components chosen as worst 
      case should be provided. 

    
    
Durability Testing - The durability testing should involve 
      cyclic loading testing several loading modes (e.g., flexion/extension, lateral 
      bending, and axial rotation) and involve a minimum of six samples of the 
      worst-case construct out to ten million cycles. This test can either be 
      combined to incorporate all testing directions into one test, or separated 
      into each loading mode. Durability testing establishes loading direction, 
      stability of the device, and wear generation potential. Clinical justification 
      for the loads and angles chosen should be provided. 

    
    
Static Compression - The testing should involve a minimum 
      of five samples of the worst case construct. As with the fatigue testing, 
      the components tested and the loading mode should be justified.

    
    
Other potential tests - 

      

        
Migration/Expulsion testing
        
Static and Dynamic Shear Testing
        
Creep and Strees Relaxation Testing
      
      
Examples of the types of construct testing typically performed for a 
        given type of spinal system in order to establish relative safety are 
        as follows:
    
    
For vertebral disc replacements, static and fatigue tests in multiple 
      loading modes should be provided out to 10 million cycles.

    
    
For a stabilization pedicle screw system intended for non-fusion, dynamic 
      shear testing and torsion testing should be provided. 

    
    
For nucleus replacements, expulsion testing should be provided.

    
    
For nucleus replacements, fatigue compression tests on new and “aged” 
      devices should be provided. 

    
    
For devices with polymer components (e.g., polyethylene cords, poyletheretherketone 
      components, etc) creep and/or stress relaxation testing should be provided.

    
    
Depending on the design of the system, the sponsor may need to perform 
      different tests in lieu of those identified above, perform additional tests 
      in different testing modes, provide testing on individual components of 
      the subject system, etc.
    
While there is a voluntary testing standard available for pedicle screw 
      systems intended for fusion and intervertebral body fusion devices (i.e., 
      ASTM F1717 and ASTM 2077, respectively), many sponsors use modified versions 
      to address different types of spinal systems. Because there are testing 
      standards in development, sponsors are advised to contact appropriate standards 
      bodies (e.g., ASTM, ISO) for information regarding test set-ups, parameters, 
      etc. for their specific device type.
    
Please comment on the currently recommended preclinical mechanical, debris, 
      or wear testing to evaluate new materials, device properties/integrity and 
      wear debris for fusion and non-fusion devices.

    
    
Discuss what additional testing, if any, should be added to current testing 
      recommendations for the following devices 

      

        
Stabilization devices for non-fusion
        
Intervertebral disc/joint replacements (cervical/thoracolumbar)
        
Devices manufactured out of new materials.
        
Intervertebral disc nucleus replacements
      
    
  
  
 
 
    
2. The FDA is currently recommending that any device in the area of the 
      spinal cord and nerve roots, that has the potential to generate debris, 
      be tested for neurotoxicity. For those incorporating new materials (e.g.., 
      polymers, composites, etc.) or designs, both fusion and non fusion, the 
      FDA recommends that manufacturers perform wear simulations and fatigue tests 
      to evaluate the potential for the device to generate wear debris. The FDA 
      believes the wear debris generated from these tests should be collected 
      and characterized. For those devices where toxicity may be an issue, the 
      FDA suggests two options to evaluate neurotoxicity:
    

      
Injection study of various sized particles into the spinal cord area 
        of small animals
      
Functional animal models
    
    
Because of the limitations of the current testing methods and models, should 
      devices made of new materials and/or those intended to retain motion be 
      tested for neurotoxicity independent of the type of material or the amount 
      of wear debris generated? If you suggest that testing be performed, please 
      describe the testing you recommend. For example,
    

      
Discuss viability and usefulness of injection animal study including 
        amount and distribution of sizes and shapes of wear debris should be injected 
        in the animal in predicting what may occur clinically for the life of 
        the implant;
      
Discuss recommendations, viability and usefulness of functional animal 
        models in predicting what may occur clinically for the life of the implant; 
        or 
      
Discuss alternatives.
    
  

II. Clinical Questions

1. For spinal assemblies not intended to fuse motion segments (Non-fusion spinal devices, e.g., disc replacement devices, nucleus replacement devices, joint replacement, spinal stabilization without fusion, etc.), the goals of treatment may be to stabilize the spine, maintain “normal/functional” motion, treat disease early in its course to prevent further progression and to conserve motion instead of fusing segments of the spine to alleviate pain and restore function. These types of devices provide challenges in choosing the best methods to evaluate safety and effectiveness.

Our current Spinal Guidance describes methods to assure that data collected provide adequate characterization of the safety and effectiveness of devices. These sections suggest appropriate patient inclusion and exclusion criteria (Section 4 and 5), effectiveness evaluations (Section 8: 8.1-8.4) safety evaluations (Section 9) and patient and study success criteria (Section 10). The FDA believes that the populations and goals of treatment may be different for devices that maintain functional motion. Therefore:

a. Please discuss study designs which may be better suited to evaluate Non-Fusion spinal devices. In your discussion, please comment on:

i. enrollment criteria,
ii. patient populations,
iii. controls,
iv. success criteria and
v. goals of the study
that would be suitable for these types of Non-fusion spinal devices

b. Devices intended to stabilize the spine yet retain functional motion are expected to have an upper limit of motion beyond which one would consider the device to be unstable and a lower limit below which one would consider the device to have inadequate motion or possibly even consider the segment to be fused. Please discuss the amount of motion and on what scale, to define a patient as a functional and clinical success (i.e., a clinically significant improvement in condition) for each of cervical, thoracic and lumbar levels for Non-Fusion spinal devices.