**FDA Proposal for the reclassification of**

**the Intervertebral body fusion device**

**Regulatory History of the** **Intervertebral Body Fusion Device**
**(Cage):**

The intervertebral body fusion device (cage) was first 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 classification 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 as a Class III,
Post-Amendments device. Presently, there is not a codified regulation
number and device identification for this device. New devices require an
premarket approval under section 515 of the act to allow commercial
distribution. 

Since 1996, CDRH has approved seven 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**

 

+------------+--------+---------+---------------------+------+-------+
| *          | *      | **Appl  | **Characteristics** | **   | **App |
| *Product** | *Appli | ication |                     | Indi | roval |
|            | cation | N       |                     | cati | D     |
|            | Ho     | umber** |                     | on** | ate** |
|            | lder** |         |                     |      |       |
+------------+--------+---------+---------------------+------+-------+
| BAK-L      | Sulz   | P950002 | -   Hollow,         | Lu   | 09-   |
|            | er-Spi |         |     threaded        | mbar | 20-96 |
| BAK        | netech |         |     cylinder        |      |       |
| Proximity  |        |         |                     |      |       |
|            |        |         | -   Titanium Alloy  |      |       |
| BAK Vista  |        |         |     (BAK-L,         |      |       |
|            |        |         |     Proximity) or   |      |       |
|            |        |         |                     |      |       |
|            |        |         | > PEEK (BAK Vista)  |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   UHMWPE Endcaps  |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   2 device/spinal |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     autograft       |      |       |
+------------+--------+---------+---------------------+------+-------+
| Ray TFC    | S      | P950019 | -   Hollow,         | Lu   | 10-   |
|            | tryker |         |     threaded        | mbar | 29-96 |
| Ray TFC    |        |         |     cylinder        |      |       |
| Unite      | How    |         |                     |      |       |
|            | medica |         | -   Titanium body   |      |       |
|            |        |         |                     |      |       |
|            | Ost    |         | -   UHMWPE Endcaps  |      |       |
|            | eonics |         |                     |      |       |
|            |        |         | -   2 device/spinal |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     autograft       |      |       |
+------------+--------+---------+---------------------+------+-------+
| Lumbar I/F | Depuy  | P960025 | -   Parallel box    | Lu   | 02-   |
| Cage       |        |         |                     | mbar | 02-99 |
|            | A      |         | -   PEEK with       |      |       |
|            | cromed |         |     carbon fiber    |      |       |
|            |        |         |                     |      |       |
|            |        |         | -                   |      |       |
|            |        |         |   Inferior/superior |      |       |
|            |        |         |     teeth           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   2               |      |       |
|            |        |         |     devices/spinal  |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     autograft       |      |       |
+------------+--------+---------+---------------------+------+-------+
| Interfix   | Med    | P970015 | -   Hollow threaded | Lu   | 05-   |
|            | tronic |         |     cylinder        | mbar | 14-99 |
| Interfix   |        |         |                     |      |       |
| RP         | S      |         | -   Titanium        |      |       |
|            | ofamor |         |                     |      |       |
| LT-Cage    |        |         | -   Endcaps         |      |       |
|            | Danek  |         |                     |      |       |
|            |        |         | -   2               |      |       |
|            |        |         |     devices/spinal  |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     autograft       |      |       |
+------------+--------+---------+---------------------+------+-------+
| BAK-C      | Sulzer | P980048 | -   Hollow,         | Cerv | 04-   |
|            | medica |         |     threaded        | ical | 20-01 |
|            |        |         |     cylinder        |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Titanium body   |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   UHMWPE Endcaps  |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   2 device/spinal |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     autograft       |      |       |
+------------+--------+---------+---------------------+------+-------+
| Affinity   | Med    | P000028 | -   Hollow,         | Cerv | 06-   |
|            | tronic |         |     threaded        | ical | 13-02 |
|            |        |         |     cylinder        |      |       |
|            | S      |         |                     |      |       |
|            | ofamor |         | -   Titanium body   |      |       |
|            |        |         |                     |      |       |
|            | Danek  |         | -   UHMWPE Endcaps  |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   2 device/spinal |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     autograft       |      |       |
+------------+--------+---------+---------------------+------+-------+
| Infuse     | Med    | P000058 | -   Hollow,         | Lu   | 07-   |
|            | tronic |         |     threaded        | mbar | 02-02 |
|            |        |         |     cylinder        |      |       |
|            | S      |         |                     |      |       |
|            | ofamor |         | -   Titanium body   |      |       |
|            |        |         |                     |      |       |
|            | Danek  |         | -   UHMWPE Endcaps  |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   2 device/spinal |      |       |
|            |        |         |     level           |      |       |
|            |        |         |                     |      |       |
|            |        |         | -   Used with       |      |       |
|            |        |         |     rhBMP2 and      |      |       |
|            |        |         |     collagen sponge |      |       |
+------------+--------+---------+---------------------+------+-------+

# 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 vertebral body replacement device
(VBR), manufactured either from titanium alloy or from polymers (e.g.,
polyetheretherketone) using autograft or allograft is 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 device using autograft, we reviewed the
adverse event reports submitted to the agency via the Medical Device
Reporting (MDR) System. The MDRs for the intervertebral body fusion
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       | **Percent Total   |
|                              | MDRs**            | MDRs**            |
+------------------------------+-------------------+-------------------+
| [Device Related]{.underline} | 23                | 25.8              |
|                              |                   |                   |
| Displacement                 | 1                 | 1.1               |
|                              |                   |                   |
| Displacement & Fracture      | 5                 | 5.6               |
|                              |                   |                   |
| Drop through during surgery  | 2                 | 2.2               |
|                              |                   |                   |
| Endcap separation            | 9                 | 10.1              |
|                              |                   |                   |
| Extrusion                    | 20                | 22.5              |
|                              |                   |                   |
| Fracture                     | 29                | 32.6              |
|                              |                   |                   |
| Unknown                      |                   |                   |
+------------------------------+-------------------+-------------------+
| [Patient                     | 2                 | 2.2               |
| Related]{.underline}         |                   |                   |
|                              | 18                | 20.2              |
| Bleeding                     |                   |                   |
|                              | 1                 | 1.1               |
| Pain                         |                   |                   |
|                              | 7                 | 7.9               |
| Infection                    |                   |                   |
|                              | 15                | 16.9              |
| Surgical time extended       |                   |                   |
|                              | 51                | 57.3              |
| Pseudoarthrosis              |                   |                   |
|                              |                   |                   |
| Secondary Surgery            |                   |                   |
+------------------------------+-------------------+-------------------+

 

 

Nine 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 device using
autograft. They also describe some potential risks of using these
devices. 

These 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]{.underline}:         | Surgeon training          |
| injuries to the vena cava; iliac vein    |                           |
| hypogastric vein; segmental vein         | Product labeling          |
| bleeder; sacral vein injury; superficial |                           |
| bleeder                                  |                           |
+------------------------------------------+---------------------------+
| [Neurological injuries:]{.underline}     | Surgeon training          |
| dural tear*,* footdrop; nerve root       |                           |
| injuries; foraminal stenosis; reflex     | Product labeling          |
| 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                   |                           |
+------------------------------------------+---------------------------+
| [Urological events;]{.underline}         | Surgeon training          |
| retrograde ejaculation                   |                           |
|                                          | Product labeling          |
+------------------------------------------+---------------------------+
| [Other]{.underline}*:* bleeding, pain,   | Surgeon training          |
| infection, adverse tissue reaction,      |                           |
| donor site pain                          | Biocompatibility data     |
|                                          |                           |
|                                          | Material standards        |
|                                          |                           |
|                                          | Product labeling          |
+------------------------------------------+---------------------------+
| [Spinal events:]{.underline} non-union,  | Surgeon training          |
| bone-fracture, subsidence, disc space    |                           |
| collapse, failure of biological fixation | Product labeling          |
+------------------------------------------+---------------------------+
| [Device Related Events:]{.underline}     | Surgeon training          |
| implant loosening, implant end-cap       |                           |
| separation, implant extrusion/migration, | Product labeling          |
| mal-positioned implant, implant          |                           |
| fracture, deformation or wear.           | 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 device using
autograft may be reclassified to a lower classification (Class II,
special controls).  Devices of this generic type have been regulated by
CDRH since 1996. During this time the agency believes a sufficiently
large body of clinical and preclinical data has become available that
indicate that these generic devices when used in accordance with their
approved labeling demonstrate relative safety and effectiveness. The
information in the literature and MDRs have identified the greatest
potential risks to health associated with intervertebral body device
use.  These risks to health are identified in Table 2.  The Agency
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 CFR LISTING for the** **Intervertebral Body Fusion Device**

 

\(a\) Intervertebral body fusion device---

\(1\) Identification. The intervertebral body fusion device is an
implanted single or multiple component spinal device 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., hollow, threaded cylinder; mesh cylinder; fenestrated rectangular
blocks; trapezoidal cubes; or wedge shaped solids). These constructs may
contain end-caps. The implant is available in a range of sizes and may
be angled to fit the patient\'s anatomical and physiological
requirements. The implant 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 interbody
fusion device is 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. The implant
is intended 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."

**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

4.  

5.  associated with this device.