FDA Proposal for the reclassification of

the Intervertebral body fusion devicePROPOSAL to RECLASSIFY

Intervertebral Body Fusion Devices

 

 

 

 

Regulatory History of the Intervertebral Body Fusion Device s (Cages):

 

The iIntervertebral body fusion devices (cages) was first have been marketed in the United States, after the Medical Device Amendments of 1976 (the 1976 Amendments) to the Food, Drug and Cosmetic Act (the Act) (21 USC 360C) as Class III, post-amendments devices requiring an approved Premarket Approval Application prior to marketing. 

 

The 1976 Amendments as amended by the Safe Medical Device Act (SMDA) of 1990 and the FDA Modernization Act (FDAMA) of 1997 provide regulations for the reclassification and regulation of medical devices intended for human use.  FDA may elect to reclassify a medical device, including the Class III medical devices into a lower regulatory class that can reasonably assure their safety and effectiveness for their intended use.

 

The Act established three categories (classes) of medical devices depending on the regulatory controls needed to provide reasonable assurance of their safety and effectiveness.  The three classes are Class I (general controls), Class II (special controls), and Class III (pre-market approval).  General controls are sufficient to provide reasonable assurance of the safety and effectiveness of Class I devices.  General controls include the following: prohibition against adulterated or misbranded devices, premarket notification (510(k)), banned devices, the quality system regulation that includes design controls and good manufacturing processes (GMPs), registration of manufacturing facilities, listing of device types, record keeping, etc.

 

Class II devices are those that cannot be classified into Class I because general controls by themselves are insufficient to provide reasonable assurance of the safety and effectiveness of such devices.  These devices are regulated using special controls and general controls.  Special controls include guidelines (guidance documents), performance standards, postmarket surveillance, clinical data, labeling, tracking requirements, and other appropriate actions the Secretary of the Department of Health and Human Services deems necessary to provide such assurance.

 

Class III devices are those for which insufficient information exists to determine that general and special controls are sufficient to provide reasonable assurance of the safety and effectiveness.  These devices are life sustaining, life supporting, or substantially important in preventing impairment of human health, or they present unreasonable risk of illness or injury.  Class III devices are regulated by using “valid scientific evidence” to establish the safety and effectiveness of the device.  Valid scientific evidence includes well-controlled investigations, partially-controlled studies, uncontrolled studies, well-documented case histories, and reports of significant human experience.

 

When most devices were classified in the late 1970s and early 1980s, most Class I and Class II devices were cleared for marketing via the 510(k) process.  Some Class I devices were also exempted from 510(k) clearance.  Now many Class I devices and a few Class II devices are exempt from 510(k) clearance because their safety and effectiveness can be reasonably assured by other general controls, particularly by the quality system regulation general control.

 

FDA has regulated the intervertebral body fusion device s as a Class III, Post-Amendments device.  Presently, there is not a codified regulation number and product definitiondevice identification for this device.  associated with these types of devices.   As of May 28, 1976, they have requiredNew devices require an premarket approval under section 515 of the act to allow commercial distribution. 

 

Since 19976, CDRH has approved sevensix intervertebral body fusion device PMAs:  .  six PMA devices using autograft and one PMA device as a combination product.  Table 1 identifies intervertebral body fusion devices which have received PMA approval:

 

 

Table 1:  Intervertebral Body Fusion Devices with PMA Approval

 

Product

Application Holder

Application Number

Characteristics

Indication

Approval Date

BAK-L

BAK Proximity

BAK Vista

 

 

Sulzer-Spinetech

P950002

§      Hollow, threaded cylinder

§      Titanium Alloy (BAK-L, Proximity) or

     PEEK (BAK Vista)

§      UHMWPE Endcaps

§      2 device/spinal level

§      Used with autograft

Lumbar

09-20-96

 

Ray TFC

Ray TFC Unite

Stryker

Howmedica

Osteonics

P950019

§      Hollow, threaded cylinder

§      Titanium body

§      UHMWPE Endcaps

§      2 device/spinal level

§      Used with autograft

Lumbar

10-29-96

Lumbar I/F Cage

Depuy

Acromed

P960025

§      Parallel box

§      PEEK with carbon fiber

§      Inferior/superior teeth

§      2 devices/spinal level

§      Used with autograft

Lumbar

02-02-99

Interfix

Interfix RP

LT-Cage

Medtronic

Sofamor

Danek

P970015

§      Hollow threaded cylinder

§      Titanium

§      Endcaps

§      2 devices/spinal level

§      Used with autograft

Lumbar

05-14-99

BAK-C

Sulzermedica

P980048

§      Hollow, threaded cylinder

§      Titanium body

§      UHMWPE Endcaps

§      2 device/spinal level

§      Used with autograft

Cervical

04-20-01

Affinity

Medtronic

Sofamor

Danek

P000028

§      Hollow, threaded cylinder

§      Titanium body

§      UHMWPE Endcaps

§      2 device/spinal level

§      Used with autograft

Cervical

06-13-02

AffinityInfuse

Medtronic

Sofamor

Danek

P000028P000058

§      Hollow, threaded cylinder

§      Titanium body

§      UHMWPE Endcaps

§      2 device/spinal level

§      Used with autograftrhBMP2 and collagen sponge

CervicalLumbar

07-02-0206-13-02

 


Risks to Health

 

FDA regulates many other spinal devices manufactured from similar materials using autograft or allograft as Class III, Class II, and unclassified devices.  For example, spinal plates and pedicle screw systems, manufactured from titanium or titanium alloy, are regulated as a Class II medical devices.  The vVertebral body replacement devices (VBRs), manufactured either from titanium alloy or from polymers (e.g., polyetheretherketone) using autograft or allograft isare also regulated as Class II medical devices.

 

FDA is not including for consideration combination products such as the intervertebral body fusion device using bone morphogenic proteins and scaffolds because of the new questions of safety and effectiveness raised by these combination products and the current inability to identify special controls to address the risks associated with these products.

 

In order to summarize the potential risks associated with the use of the intervertebral body fusion devices using autograft, we reviewed the adverse event reports submitted to the agency via the Medical Device Reporting (MDR) System.  which was voluntary from 1992 until 1996 when it became mandatory for manufacturers to report any device failures they were aware ofThe MDRs for the intervertebral body fusion devices received by the Agency from 1996 to the present are summarized in Table 2.

 

 

Table 2: Adverse Events Reported via MDR

 

Adverse Event

Number of MDRs

Percent Total MDRs

 

Device Related

 

Displacement

Displacement & Fracture

Drop through during surgery

Endcap separation

Extrusion

Fracture

Unknown

 

 

 

23

1

5

2

9

20

29

 

 

 

25.8

1.1

5.6

2.2

10.1

22.5

32.6

 

Patient Related

 

Bleeding

Pain

Infection

Surgical time extended

Pseudoarthrosis

Secondary Surgery

 

 

 

2

18

1

7

15

51

 

 

 

2.2

20.2

1.1

7.9

16.9

57.3

 

 

Nine The following literature articles, published between 1997 and 2003, in the bibliography for this proposed reclassification are indicative of the published literature on the intervertebral body fusion devices using autograft. They, and  discuss intervertebral body fusion devices and also describe some potential risks of using these devices. 

 

1.   Christensen FB, Hansen ES, Eiskjaer SP, Hoy K, Helmig P, Neumann P, Niedermann B, Bunger CE. 
Circumferential lumbar spinal fusion with Brantigan cage versus posterolateral fusion with titanium Cotrel-Dubousset instrumentation: a prospective, randomized clinical study of 146 patients.
Spine. 2002 Dec 1;27(23):2674-83. 
 
2.   Hodges SD, Humphreys SC, Eck JC, Murphy RB. 
Intraoperative loosening of Bagby and Kuslich cages during anterior lumbar interbody fusion.
J Spinal Disord. 2000 Dec;13(6):535-7. 
 
3.   Hacker RJ, Cauthen JC, Gilbert TJ, Griffith SL. 
A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage.
Spine. 2000 Oct 15;25(20):2646-54; discussion 2655. 
 
4.   Kuslich SD, Danielson G, Dowdle JD, Sherman J, Fredrickson B, Yuan H, Griffith SL. 
 Four-year follow-up results of lumbar spine arthrodesis using the Bagby and Kuslich lumbar fusion cage.
Spine. 2000 Oct 15;25(20):2656-62. 

 
5.   Brantigan JW, Steffee AD, Lewis ML, Quinn LM, Persenaire JM. 
Lumbar interbody fusion using the Brantigan I/F cage for posterior lumbar interbody fusion and the variable pedicle screw placement system: two-year results from a Food and Drug Administration investigational device exemption clinical trial.
Spine. 2000 Jun 1;25(11):1437-46. 
 
6.   Matge G, Leclercq TA. 
Rationale for interbody fusion with threaded titanium cages at cervical and lumbar levels. Results on 357 cases.
Acta Neurochir (Wien). 2000;142(4):425-33; discussion 434. 
 
7.   Agazzi S, Reverdin A, May D. 
Posterior lumbar interbody fusion with cages: an independent review of 71 cases.
J Neurosurg. 1999 Oct;91(2 Suppl):186-92. 
 
8.   Kuslich SD, Ulstrom CL, Griffith SL, Ahern JW, Dowdle JD. 
The Bagby and Kuslich method of lumbar interbody fusion. History, techniques, and 2-year follow-up results of a United States prospective, multicenter trial.
Spine. 1998 Jun 1;23(11):1267-78; discussion 1279. 
 
9.   Ray CD. 
   Threaded titanium cages for lumbar interbody fusions.
Spine. 1997 Mar 15;22(6):667-79; discussion 679-80. 

 

TThese articles, as well as others, and intervertebral body fusion device labels were reviewed in order to compile the risks identified in Table 3.  Tables 3 also identifies the methods that will be proposed to ameliorate these risks.

 



Table 3:  Table of Potential Risks and Controls 

 

Potential Risk

Control

Vascular injuries:  injuries to the vena cava; iliac vein hypogastric vein; segmental vein bleeder; sacral vein injury; superficial bleeder

 

Animal studies

Clinical dataSurgeon training

Product labeling

Neurological injuries:  dural tear,  footdrop; nerve root injuries; foraminal stenosis; reflex sympathetic dystrophy; numbness, warmth   or burning of legs; dysthesia; paresthesia; shooting pain in lower back, radiculopathy

with tingling extremities; back and leg pain with other symptoms; de-nervated abductor magnus muscle

 

Surgeon training

Animal studies

Clinical data

Product labeling

Urological eEvents;  retrograde ejaculation

 

Surgeon training

Animal studies

Clinical data

Product labeling

Other:  bleeding, pain, infection, adverse tissue reaction, donor site pain

 

Surgeon training

Animal studies

Clinical data

Biocompatibility data

Material standards

Product labeling

Spinal eEvents:  non-union, bone-fracture,  subsidence, disc space collapse, failure of biological fixation

 

Surgeon training

Animal studies

Clinical data

Product labeling

Device Related Events: implant loosening, implant end-cap separation, implant extrusion/migration, mal-positioned implant, implant fracture, deformation or wear.,

Surgeon training

Animal studies

Clinical data

Product labeling

Mechanical testing standards

Guidance documents

Product labeling

 

 

Special Controls:

 

The special control used to ameliorate risks associated with the intervertebral body fusion device will be a guidance document entitled “Class II Special Controls Guidance:  Intervertebral Body Fusion Device.”   This guidance, will describe compliance with the following:

 

·         material standards (e.g. ASTM F-136-02:  Standard Specification for Wrought Titanium-6Alumnium-4Vanadium ELI Alloy for Surgical Implant Applications; ASTM F-2026-02 Standard Specification for Polyetheretherketone (PEEK) Polymers for Surgical Implant Applications);

 

·         mechanical testing standards (e.g., F2077-03 Test Methods For Intervertebral Body Fusion Devices;

 

·         biocompatibility standards (e.g., ISO 10993 – Biological Evaluation of Medical Devices); and

 

·         labeling.

 

 


Proposed Reclassification:

 

The Agency is proposing that the intervertebral body fusion devices using autograft may be reclassified to a lower classification (Class II, special controls).  These devices have beenDevices of this generic type have been regulated by CDRH since 19976.  During this time the agency believes a sufficiently large body of clinical and preclinical data has become available that indicate a great deal of clinical and preclinical data has been collected that indicate that these generic devices when used in accordance with their approved labeling demonstrate relative safety and effectiveness.  when used for spinal fusion and when used in accordance with their approved labeling.  The data reportedinformation in the literature and medical device reportingMDRs have identified the greatest potential risks to the patientshealth associated with intervertebral body device use.  These risks to health are identified in Table 2.  The Agency feels believes that all of these potential risks can be addressed via special controls in the form of a guidance document. 

 

The applications affected by this reclassification would include all of those listed in Table 1.  The products within this category are currently manufactured from the following materials:

 

·         Titanium alloy (Ti-6Al-4V) conforming to American Society Testing and Materials (ASTM) Standard F136 

 

·         Polyetheretherketone (PEEK) reinforced with carbon fiber.

 


Proposed Identification for Intervertebral Body Fusion Devices for the Code of Federal Regulations:

 

Currently, there is not a CFR listing for Intervertebral Body Fusion Devices.

 

PROPOSED CFR LISTING for the Intervertebral Body Fusion Devices

 

(a) Intervertebral body fusion devices

(1) Identification. .  The iIntervertebral body fusion devices is an implantedare single or multiple component spinal devices, made from a variety of materials, including titanium alloys (e.g.  Ti-6Al-4V) and polymers (e.g., polyetheretherketone (PEEK)). ) Such a spinal implant assembly consists of a construct intended to fill the intervertebral body space (e.g., hHollow, threaded cylinder; mesh cylinder; fenestrated rectangular blocks; trapezoidal cubes; or wedge shaped solids).  These constructs may contain end-caps.  The implant iss are available in a range of sizes and may be angled to fit the patient's anatomical and physiological requirements.  The implants may have a variety of features, some of which include spiked teeth on the inferior and superior surfaces of the implant and through-holes intended to allow bony ingrowth.  The iInterbody fusion device is s are intended for spinal fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one or two levels from C2-C7 and L2-S1.  DDD is defined as discogenic neck/back pain with degeneration of the disc confirmed by patient history and radiographic studies.  These DDD patients may also have up to Grade I spondylolisthesis or retrolisthesis at the involved level.  Cage implantsThe implant is intendedare to be used with autogenous bone graft and implanted via a laparoscopic, an open posterior approach,  or an open anterior approach.

(2) Classification.  Class II (special controls).  The special control for the device is the guidance document entitled “Class II Special Controls Guidance:  Intervertebral Body Fusion Device.” Intervertebral body fusion devices must comply with the following special controls:

      (i) Compliance with material standards,
      (ii) Compliance with mechanical testing standards,
      (iii) Compliance with biocompatibility standards, and
      (iv) Labeling 

 

 


Questions for the Panel:

 

1.       Please discuss the descriptive information and intended use presented in the reclassification identification.

 

2.       Please discuss any specific pre-clinical testing criteria you believe are needed to characterize the intervertebral body fusion device.

3.       Please discuss the risks to health for the intervertebral body fusion device.

 

4.   Please discuss any other risks to health for these devices that have not been presented.

 

5.   Please discuss any additional special controls needed to adequately control the risks

1.      associated with this device.

 

 

We have proposed a description of an intervertebral body fusion device that is limited by material composition and design characteristics.  Do you believe the limitations proposed for a Class II classification are appropriate?

How do you believe intervertebral body fusion devices manufactured from other materials (e.g., resorbable materials) and with other design characteristics (e.g., designs with moving parts) should be classified?

Do you believe that a Class II intervertebral body fusion device should be limited to use with supplemental fixation?

Do you believe that intervertebral body fusion devices, which include holes for bony ingrowth should have limitations imposed on the sizes of holes. 

Do you believe Objective Performance Criteria (e.g., mechanical test criteria) should be imposed for the mechanical testing of intervertebral body fusion devices?

Are you aware of any additional risks or concerns pertaining to intervertebral body fusion devices?

Do you believe an additional special controls would benefit the regulation of intervertebral body fusion devices?