[Federal Register Volume 71, Number 27 (Thursday, February 9, 2006)]
[Proposed Rules]
[Pages 6710-6713]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-1736]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 888

[Docket No. 2006N-0019]


Orthopedic Devices; Reclassification of the Intervertebral Body 
Fusion Device

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
reclassify intervertebral body fusion devices that contain bone 
grafting material, from class III (premarket approval) into class II 
(special controls), and retain those that contain any therapeutic 
biologic (e.g., bone morphogenic protein) in class III. Elsewhere in 
this issue of the Federal Register, FDA is announcing the availability 
of a draft guidance document that would serve as the special control if 
FDA reclassifies this device. The agency is proposing this 
reclassification based on the recommendation of the Orthopaedic and 
Rehabilitation Devices Panel (the Panel).

DATES: Submit written or electronic comments by May 10, 2006. See 
section X of this document for the proposed effective date of a final 
rule based on this proposed rule.

ADDRESSES: You may submit comments, identified by Docket No. 2006N-
0019, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.

Written Submissions

    Submit written submissions in the followings ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/courier (for paper, disk, or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name 
and docket number for this rulemaking. All comments received may be 
posted without change to http://www.fda.gov/ohrms/dockets/default.htm, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Jodi N. Anderson, Center for Devices 
and Radiological Health (HFZ-410), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-2036, ext. 186.

SUPPLEMENTARY INFORMATION:

I. Background (Regulatory Authorities)

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 
et seq.), as amended by the Medical Device Amendments of 1976 (the 1976 
amendments) (Public Law 94-295), the Safe Medical Devices Act of 1990 
(Public Law 101-629), the Food and Drug Administration Modernization 
Act of 1997 (Public Law 105-115), and the Medical Device User Fee and 
Modernization Act of 2002 (Public Law 107-250), established a 
comprehensive system for the regulation of medical devices intended for 
human use. Section 513 of the act (21 U.S.C. 360c) established three 
categories (classes) of devices, depending on the regulatory controls 
needed to provide reasonable assurance of their safety and 
effectiveness. The three categories of devices are class I (general 
controls), class II (special controls), and class III (premarket 
approval).
    Under section 513 of the act, devices that were in commercial 
distribution before May 28, 1976 (the date of enactment of the 1976 
amendments), generally referred to as preamendments devices, are 
classified after FDA has done the following: (1) Received a 
recommendation from a device classification panel (an FDA advisory 
committee); (2) published the panel's

[[Page 6711]]

recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution prior to May 28, 
1976, generally referred to as postamendments devices, are classified 
automatically by statute (section 513(f) of the act) into class III 
without any FDA rulemaking process. Those devices remain in class III 
and require premarket approval, unless and until the device is 
reclassified into class I or II or FDA issues an order finding the 
device to be substantially equivalent, under section 513(i) of the act, 
to a predicate device that does not require premarket approval. The 
agency determines whether new devices are substantially equivalent to 
predicate devices by means of premarket notification procedures in 
section 510(k) of the act (21 U.S.C. 360(k)) and part 807 (21 CFR part 
807) of the regulations.
    A preamendments device that has been classified into class III may 
be marketed, by means of premarket notification procedures, without 
submission of a premarket approval application (PMA) until FDA issues a 
final regulation under section 515(b) of the act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    Reclassification of classified postamendments devices is governed 
by section 513(f ) of the act. This section provides that FDA may 
initiate the reclassification of a device classified into class III 
under section 513(f)(1) of the act, or the manufacturer or importer of 
a device may petition the Secretary of Health and Human Services (the 
Secretary) for the issuance of an order classifying the device in class 
I or class II. FDA's regulations in 21 CFR 860.134 set forth the 
procedures for the filing and review of a petition for reclassification 
of such class III devices. In order to change the classification of the 
device, it is necessary that the proposed new class have sufficient 
regulatory controls to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use.
    Under section 513(f)(3)(B)(i) of the act, the Secretary may, for 
good cause shown, refer a proposed reclassification to a device 
classification panel. The Panel shall make a recommendation to the 
Secretary respecting approval or denial of the proposed 
reclassification. Under section 513(f)(3)(B)(i), any such 
recommendation must contain the following: (1) A summary of the reasons 
for the recommendation, (2) a summary of the data upon which the 
recommendation is based, and (3) an identification of the risks to 
health (if any) presented by the device with respect to which the 
proposed reclassification was initiated.

II. Regulatory History of the Device

    The intervertebral body fusion device is a postamendments device 
classified into class III under section 513(f)(1) of the act. It is 
intended for intervertebral body fusion. The intervertebral body fusion 
device cannot be placed in commercial distribution for implantation 
unless it is reclassified under section 513(f)(3), or subject to an 
approved PMA under section 515 of the act.
    Based on information discussed at a December 11, 2003, Panel 
meeting (see section IV of this document) regarding the intervertebral 
body fusion device, the FDA believes potential risks associated with 
the intervertebral body fusion device, except those that contain any 
therapeutic biologic, can be addressed by special controls in the form 
of a guidance document. Thus, FDA is proposing to reclassify 
intervertebral body fusion devices that contain bone grafting material 
from class III into class II. Consistent with the act and the 
regulation, FDA referred the proposal to the Panel for its 
recommendation on the requested changes in classification.
    Intervertebral body fusion devices that include any therapeutic 
biologic (e.g., bone morphogenic protein) will remain in class III. FDA 
believes that there is insufficient information to determine that 
general and special controls would provide a reasonable assurance of 
their safety and effectiveness.

III. Device Description

    The following device description is based on the Panel's 
recommendation and the agency's review:
    An intervertebral body fusion device is an implanted single or 
multiple component spinal device made from a variety of materials, 
including titanium and polymers. The device is inserted into the 
intervertebral body space of the cervical or lumbosacral spine, and is 
intended for intervertebral body fusion.

IV. Recommendation of the Panel

    At a public meeting on December 11, 2003, the Panel recommended 
unanimously that the intervertebral body fusion device, except those 
that contain any therapeutic biologic, be reclassified from class III 
into class II (Ref. 1). The Panel believed that class II with special 
controls, in addition to the general controls, would provide reasonable 
assurance of the safety and effectiveness of the device. The Panel also 
recommended that the proposed special controls for the device be 
mechanical, animal, and clinical testing, labeling, sterilization, and 
biocompatibility as suggested by FDA staff.

V. Risks to Health

    After considering the information in the Panel's recommendation, as 
well as other information, including Medical Device Reports (MDRs), FDA 
has evaluated the risks to health associated with use of the 
intervertebral body fusion device that contains bone grafting material 
and determined that the following risks to health are associated with 
its use:

A. Infection

    Infection of the soft tissue, bony tissue, and the disc space is a 
potential risk to health associated with all surgical procedures and 
implanted spinal devices. Material composition or impurities, wear 
debris, operative time, and operative environment may compromise the 
vascular supply to the area or affect the immune system, which could 
increase the risk of infection. Improper sterilization or packaging may 
also increase the risk of infection.

B. Adverse Tissue Reaction

    Adverse tissue reaction is a potential risk to health associated 
with all implanted devices. The implantation of the intervertebral body 
fusion device will elicit a mild inflammatory reaction typical of a 
normal foreign body response. Incompatible materials or impurities in 
the materials and wear debris may increase the severity of a local 
tissue reaction or cause a systemic tissue reaction. If the materials 
used in the manufacture of intervertebral body fusion device are not 
biocompatible, the patient could have an adverse tissue reaction.

C. Pain and Loss of Function

    Pain and loss of function are risks to health associated with any 
implanted spinal device. Some device-related complications that may 
cause pain and loss of function include device fracture, deformation, 
loosening, extrusion, or migration due to inappropriate patient or 
device selection. The wear of materials, which may cause osteolysis 
(dissolution of bone), and component disassembly, fracture, or failure 
may also result in pain and loss of function.

[[Page 6712]]

D. Soft Tissue Injury

    Soft tissue injury is a risk to health associated with all spinal 
surgery. This includes injury to major blood vessels, viscera, nerve 
roots, spinal cord, and cauda equina.

E. Vertebral Endplate Injury

    Vertebral endplate injury is a risk to health associated with the 
insertion of an intervertebral body fusion device. Surgically inserting 
a device with a different geometry and modulus of elasticity than bone 
may lead to vertebral fracture, sinking of the device into the 
vertebral endplate (subsidence), collapse of the local blood supply, 
and collapse of the vertebral end plate.

F. Reoperation

    Reoperation is a risk to health associated with any surgery. The 
need for reoperation could result from a failed intervertebral body 
device or component of the device, from nerve root decompression or 
adjacent level disease, or from reasons related to any surgery, e.g., 
infection or bleeding.

G. Pseudarthrosis (i.e., non-union)

    Pseudarthrosis (i.e., non-union) is a risk associated with all 
spinal fusion surgeries. It signifies failure of the bony fusion mass 
and results in persistent instability.

VI. Summary of the Reasons for the Reclassification

    FDA believes that the intervertebral body fusion device that 
contains bone grafting material should be reclassified into class II 
because special controls, in addition to general controls, will provide 
reasonable assurance of the safety and effectiveness of the device. In 
addition, there is sufficient information to establish special controls 
to provide such assurance.

VII. Summary of the Data Upon Which the Reclassification is Based

    As discussed previously in this document, FDA is proposing this 
reclassification based on the Panel's recommendation. In addition FDA 
has reviewed MDRs related to this device. After evaluating this 
information, FDA believes that the potential risks to health associated 
with use of the intervertebral body fusion device described in section 
V of this document can be addressed by special controls. In addition, 
there is reasonable knowledge of the benefits of the device, including 
the provision of mechanical support, which aids in fusion procedures of 
the anterior spinal column.

VIII. Special Controls

    FDA believes that the draft guidance document entitled ``Class II 
Special Controls Guidance Document: Intervertebral Body Fusion Device'' 
(the class II special controls guidance document), in addition to 
providing general controls, can address the risks to health associated 
with the use of the device and described in section V of this document. 
FDA believes further that the class II special controls guidance 
document, which incorporates voluntary consensus standards and labeling 
recommendations, addresses the Panel's concerns regarding the content 
of a special controls guidance document. Elsewhere in this issue of the 
Federal Register, FDA is publishing a notice of availability of the 
draft guidance document that the agency intends to use as the special 
control for this device.
    The class II special controls guidance document contains specific 
recommendations with regard to device performance testing and other 
information FDA believes should be included in premarket notification 
submissions (510(k)s) for the intervertebral body fusion device that 
contains bone grafting material. Sections of the draft special controls 
guidance document address the following topics: Material 
characterization, mechanical testing, animal testing, clinical testing, 
sterility, biocompatibility, and labeling. FDA has identified the risks 
to health associated with the use of the device in the first column of 
table 1 of this document and the recommended mitigation measures 
identified in the class II special controls guidance document in the 
second column.

                                Table 1.
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         Identified Risk              Recommended Mitigation Measures
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Infection                         Sterility
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Adverse Tissue Reaction           Biocompatibility
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Pain and Loss of Function         Mechanical Testing
                                  Animal Data
                                  Clinical Data
                                  Labeling
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Soft Tissue Injury                Labeling
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Vertebral Endplate Injury         Material Characterization
                                  Mechanical Testing
                                  Biocompatibility
                                  Labeling
------------------------------------------------------------------------
Reoperation                       Labeling
------------------------------------------------------------------------
Psuedoarthrosis (i.e., non-       Labeling
 union)
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    Following the effective date of a final rule based on this 
proposal, any firm submitting a 510(k) premarket notification for an 
intervertebral body fusion device will need to address the issues 
covered in the special controls guidance. However, the firm need only 
show that its device meets the recommendations of the guidance or in 
some other way provides equivalent assurance of safety and 
effectiveness.

IX. FDA's Findings

    FDA believes the intervertebral body fusion device that contains 
bone grafting material should be reclassified into class II because 
special controls, in addition to general controls, can provide 
reasonable assurance of the safety and effectiveness of the device. In 
addition, there is sufficient information to establish special controls 
to provide such assurance. FDA, therefore, is proposing to reclassify 
the intervertebral body fusion device that contains bone grafting 
material into class II and establish the class II special controls 
guidance document as the special control for that device, and to retain 
in class III those devices that contain any therapeutic biologic.

X. Effective Date

    FDA proposes that any final rule that may issue based on this 
proposal become effective 30 days after its date of publication in the 
Federal Register.

XI. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) that this proposed 
reclassification action is of a type that does not individually or 
cumulatively have a significant effect on the human environment. 
Therefore, neither an environmental assessment, nor an environmental 
impact statement is required.

XII. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic,

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environmental, public health and safety, and other advantages; 
distributive impacts; and equity). The agency believes that this 
proposed rule is not a significant regulatory action as defined by the 
Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Reclassification of this device from class III to 
class II will relieve all manufacturers of the device of the costs of 
complying with the premarket approval requirements in section 515 of 
the act. Because reclassification will reduce regulatory costs with 
respect to this device, the agency certifies that the proposed rule 
will not have a significant economic impact on a substantial number of 
small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $115 million, using the most current (2003) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

XIII. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed rule, if finalized, would not contain policies that would 
have substantial direct effects on the States, on the relationship 
between the National Government and the States, or on the distribution 
of power and responsibilities among the various levels of government. 
Accordingly, the agency tentatively concludes that the proposed rule 
does not contain policies that have federalism implications as defined 
in the Executive order and, consequently, a federalism summary impact 
statement has not been prepared.

XIV. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(the PRA) (44 U.S.C. 3501-3520) is not required.
    FDA also tentatively concludes that the special controls guidance 
document does not contain new information collection provisions that 
are subject to review and clearance by OMB under the PRA. Elsewhere in 
this issue of the Federal Register, FDA is publishing a notice 
announcing the availability of the draft guidance document entitled 
``Class II Special Controls Guidance Document: Intervertebral Body 
Fusion Device;'' the notice contains an analysis of the paperwork 
burden for the draft guidance.

XV. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this proposal. 
Submit a single copy of electronic comments or two paper copies of 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

XVI. References

    The following reference has been placed on display in the Division 
of Dockets Management (see ADDRESSES) and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Orthopedic and Rehabilitation Devices Panel Meeting Transcript, 
pp. 1-141, December 11, 2003.

List of Subjects in 21 CFR Part 888

    Medical devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 888 be amended as follows:

PART 888--ORTHOPEDIC DEVICES

    1. The authority citation for 21 CFR part 888 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
    2. Section 888.3080 is added to subpart D to read as follows:


Sec.  888.3080  Intervertebral body fusion device.

    (a) Identification. An intervertebral body fusion device is an 
implanted single or multiple component spinal device made from a 
variety of materials, including titanium and polymers. The device is 
inserted into the intervertebral body space of the cervical or 
lumbosacral spine, and is intended for intervertebral body fusion.
    (b) Classification. (1) Class II (special controls) for 
intervertebral body fusion devices that contain bone grafting material. 
The special control is the FDA guidance document entitled ``Class II 
Special Controls Guidance Document: Intervertebral Body Fusion 
Device.'' See Sec.  888.1(e) for the availability of this guidance 
document.
    (2) Class III (premarket approval) for intervertebral body fusion 
devices that include any therapeutic biologic (e.g., bone morphogenic 
protein). Intervertebral body fusion devices that contain any 
therapeutic biologic require premarket approval.
    (c) Date premarket approval application (PMA) or notice of product 
development protocol (PDP) is required. Devices described in paragraph 
(b)(2) of this section shall have an approved PMA or a declared 
completed PDP in effect before being placed in commercial distribution.

    Dated: February 1, 2006.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. E6-1736 Filed 2-8-06; 8:45 am]
BILLING CODE 4160-01-S