[Federal Register: June 30, 2004 (Volume 69, Number 125)]
[Proposed Rules]               
[Page 39377-39380]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30jn04-12]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 872

[Docket No. 2002P-0520]

 
Dental Devices; Tricalcium Phosphate Granules and Other Bone 
Grafting Material for Dental Bone Repair

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
reclassify tricalcium phosphate (TCP) granules for dental bone repair 
from class III to class II (special controls); classify into class II 
(special controls) all other bone grafting material for dental 
indications, except those that contain drug or biologic components; and 
revise the classification name and identification of the device. Bone 
grafting materials that contain a drug or biologic component would 
remain in class III. The proposed classification identification 
includes materials such as hydroxyapatite, demineralized bone 
additives, collagen, and polylactic acids. After considering public 
comments on the proposed reclassification and classification, FDA will 
publish a final regulation, if appropriate. This action is being taken 
to establish sufficient regulatory controls that will provide 
reasonable assurance of the safety and effectiveness of this device. 
Elsewhere in this issue of the Federal Register, FDA is publishing a 
notice of availability of a draft guidance document that the agency 
proposes to use as a special control for the device.

DATES: Submit written or electronic comments by September 28, 2004. See 
section VI of this document for the proposed effective date of a final 
rule based on this document.

ADDRESSES:  You may submit comments, identified by Docket No. 2002P-
0520, by any of the following methods:
     Federal eRulemaking Portal: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations. gov. 

Follow the instructions for submitting comments.
     Agency Web site: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. 

Follow the instructions for submitting comments on the agency Web site.
     E-mail: fdadockets@oc.fda.gov. Include Docket No. 2002P-
0520 in the subject line of your e-mail message.
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852.
    Instructions: All submissions received must include the agency name 
and Docket No. or Regulatory Information Number (RIN) for this 
rulemaking. All comments received will be posted without change to 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments, including any personal 

information provided. For detailed instructions on submitting comments 
and additional information on the rulemaking process, 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments and/or 

the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Michael E. Adjodha, Center for Devices 
and Radiological Health (HFZ-480), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850; 301-827-5283; e-mail: 
mea@cdrh.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    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 the following requirements are met: (1) FDA has 
received a recommendation from a device classification panel (an FDA 
advisory committee); (2) FDA has published the panel's recommendation 
for comment, along with a proposed regulation classifying the device; 
and (3) FDA has published a final regulation classifying the device. 
FDA has classified most preamendments devices under these procedures.
    Under section 520(l) of the act (21 U.S.C. 360j(l)), devices 
formerly regulated as new drugs are automatically classified into class 
III, unless the Secretary of Health and Human Services, in response to 
a reclassification petition, has classified the device into class I or 
II.

II. Recommendation of the Panel

A. Identification of the Device

    In the Federal Register of August 12, 1987 (52 FR 30082), FDA 
issued a final rule codifying the classification of ``tricalcium 
phosphate for dental bone repair'' as a class III device under the 1976 
amendments. At that time, FDA was not aware that bone grafting 
material, other than TCP, was a preamendments device and inadvertently 
omitted classifying it. Consistent with the act and regulations, FDA 
has since consulted with the Dental Products Advisory Panel (the 
panel), an FDA advisory committee, regarding classification of this 
device.
    On November 12, 2002, Bicon, Inc., Boston, MA, submitted a petition 
to FDA to reclassify beta-tricalcium phosphate for dental indications 
from ``Class III to Class Unclassified'' (Ref. 1). On December 9, 2002, 
the petitioner amended its petition to make clear that it was 
requesting that FDA reclassify beta-tricalcium phosphate from class III 
to class II. Beta-tricalcium phosphate and all other forms of 
tricalcium phosphate for dental bone repair, including alpha and 
amorphous forms, are transitional devices and are currently regulated 
as class III devices under 21 CFR 872.3930, ``Tricalcium phosphate 
granules for dental bone

[[Page 39378]]

repair,'' requiring premarket approval. Consistent with section 
520(l)(2) the act and the regulations in 21 CFR 860.136, FDA consulted 
with the panel regarding reclassification of this device.
    Other bone grafting materials in the form of synthetic hard tissue 
replacements have been used in dentistry since the 1970s (Ref. 2). 
Because they were inadvertently omitted from the August 12, 1987, final 
rule classifying most dental devices, these other bone grafting 
materials are unclassified preamendments devices. Although 
unclassified, they are nevertheless subject to general controls, such 
as premarket notification. TCP and other bone grafting materials share 
the same indications, risks, and recommended mitigation measures.
    FDA believes that one classification identification that 
encompasses all bone grafting materials for dental indications would 
provide a more scientifically accurate and more administratively 
transparent regulation for these materials. Therefore, FDA is 
identifying bone grafting material as a naturally or synthetically 
derived material, such as hydroxyapatite, tricalcium phosphate, 
demineralized bone additives, collagen, or polylactic acids, that is 
intended to fill, augment, or reconstruct periodontal or bony defects 
of the oral and maxillofacial region.

B. Recommended Classification of the Panel

    At the meeting of the Dental Products Advisory Panel held on May 
22, 2003, the panel voted five to zero (with no abstentions) to 
recommend that TCP for dental indications be reclassified from class 
III to class II (special controls). The panel considered all forms of 
TCP, including beta-tricalcium phosphate, and concluded that special 
controls, in addition to general controls, would provide reasonable 
assurance of the safety and effectiveness of these bone grafting 
materials devices (Ref. 3).
    In addition, on August 8 and 9, 1995, in accordance with the 
procedures set forth in 21 CFR 860.84, the panel considered 
classification of the non-TCP materials. The panel recommended 
unanimously that non-TCP bone grafting materials be classified into 
class II, except when intended to be used alone in filling or repair of 
bony defects and/or augmentation of the alveolar ridge. For that 
indication, the panel recommended placing the device in class III, but 
with a low priority for establishing an effective date for the 
requirement for premarket approval (Ref. 4).

C. Summary of Reasons for the Recommendation

    For TCP for dental indications and for bone grafting materials for 
certain dental indications, the panel believed that special controls, 
in addition to general controls, would provide reasonable assurance of 
the safety and effectiveness of these devices and that there is 
sufficient information to establish special controls to provide such 
assurance.
    The panel recommended that TCP should remain in class III when used 
alone in filling or repair of bony defects and/or augmentation of the 
alveolar ridge because they believed that the materials present risks 
to health that cannot be addressed by special controls.

D. Summary of the Data for the Recommendation

    For TCP for dental indications, the panel based its recommendation 
on the information provided by the petitioner and FDA, the 
presentations made by stakeholders and FDA at the panel meeting, the 
open discussion during the panel meeting, and the panel members' 
personal knowledge of and clinical experience with the device (Ref. 5). 
The panel did not discuss bone grafting materials containing a drug or 
biologic component.
    For non-TCP materials, the panel based its recommendation on the 
information provided by FDA, presentations made by stakeholders who 
marketed bone filling and augmentation devices, the open discussion 
during the panel meeting, and the panel members' personal knowledge of 
and clinical experience with the device.

III. Risks to Health

    The panel identified the following risks to health associated with 
bone grafting material: Ineffective bone formation, adverse tissue 
reaction, infection, and improper use.

A. Ineffective Bone Formation

    The quality and physical properties of bone grafting material may 
be insufficient to support the required loads and lead to device 
failure. Device failure may result in ineffective treatment, revision, 
and permanent impairment for the patient.

B. Adverse Tissue Reaction

    Inadequate biocompatibility of any of the components contained in 
bone grafting material may result in adverse tissue reaction and 
presents the potential for surgical revision (i.e., reoperation).

C. Infection

    Implantation of an improperly sterilized device may result in an 
infection. Infection may result in revision or explantation of the 
device, which presents the potential for permanent impairment.

D. Improper Use

    Inadequate labeling may result in improper use. Improper use may 
result in ineffective treatment and may cause permanent impairment.

IV. Proposed Rule

    FDA believes that bone grafting material that does not contain a 
drug or biologic component should be classified into class II and that 
TCP should be reclassified into class II because special controls, in 
addition to general controls, would provide reasonable assurance of the 
safety and effectiveness of the device, and there is sufficient 
information to establish special controls to provide such assurance.
    FDA disagrees with the (1995) panel's recommendation that bone 
grafting materials should remain in class III when used alone in 
filling or repair of bony defects and/or augmentation of the alveolar 
ridge. FDA believes that when used for these indications, the risks to 
health can be addressed by special controls and that all of these bone 
grafting material devices share the same risks and recommended 
mitigation measures. Accordingly, FDA has developed the draft guidance 
document entitled ``Class II Special Controls Guidance Document: Dental 
Bone Grafting Material'' to serve as the special control for TCP and 
other bone grafting material devices for dental indications. As noted 
previously, bone grafting material that contains a drug or biologic 
component would remain in class III and the special control guidance 
document would not apply.

V. Proposed Special Control

    FDA believes that the special controls guidance document entitled 
``Class II Special Controls Guidance Document: Dental Bone Grafting 
Material,'' in addition to general controls, can address the risks to 
health described in section III of this document. Elsewhere in this 
issue of the Federal Register, FDA is announcing the availability of 
the draft guidance document.
    If adopted, following the effective date of a final rule 
reclassifying and classifying the device, any firm submitting a 510(k) 
premarket notification for the device would need to address the issues 
covered in the special control guidance. However, the firm would need 
to show only that its

[[Page 39379]]

device meets the recommendations of the guidance or in some other way 
provides equivalent assurances of safety and effectiveness.
    The special controls guidance document contains recommendations 
with regard to the information and testing that should be included in a 
premarket notification. The guidance document addresses the following 
topics: Characterization, biocompatibility, sterilization, and 
labeling. Adequate characterization of the composition, physical 
properties, and in vivo performance can address the risk of ineffective 
bone formation. Adequate biocompatibility can address the risk of 
adverse tissue reaction. Sterilization can address the risk of 
infection, and labeling can address the risk of improper use.
    The agency is not proposing to exempt this device from the 
premarket notification requirements of the act, as permitted by section 
510(m) of the act (21 U.S.C. 360(m)). FDA believes that it needs to 
review information in a premarket notification submission that 
addresses the risks identified in the guidance document in order to 
assure that a new device is at least as safe and effective as legally 
marketed devices of this type.

VI. 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.

VII. Environmental Impact

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

VIII. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and 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, 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. Manufacturers of the preamendments devices that FDA 
is reclassifying are being relieved of the burden of eventually 
submitting a premarket approval application. Manufacturers of these 
devices are already subject to the premarket notification requirements. 
FDA has designated a guidance document as the special control. FDA 
believes that manufacturers, including small manufacturers, are already 
substantially in compliance with the recommendations in the guidance 
document, and they will not need to submit substantially more 
information in their premarket notification submissions in order to 
meet the recommendations in the guidance document or otherwise provide 
reasonable assurances of safety and effectiveness. FDA believes that 
any regulation based on this proposed rule will impose no significant 
economic impact on any small entities. The agency, therefore, certifies 
that this proposed rule will not have a significant impact on a 
substantial number of small entities. In addition, it will not impose 
costs of $100 million or more on either the private sector or State, 
local, and tribal governments in the aggregate, and therefore, a 
summary statement or analysis under section 202(a) of the Unfunded 
Mandates Reform Act of 1995 is not required.

IX. 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 under the Paperwork Reduction Act of 1995 (44 
U.S.C. 3501-3520) is not required.

X. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Identify comments 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.

XI. References

    The following references have 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. Petition from Bicon, Inc., Boston, MA to FDA, November 12, 
2002.
    2. Le Geros, R. Z., ``Calcium Phosphate Materials in Restorative 
Dentistry: A Review,'' Advances in Dental Research, vol. 2, pp. 164-
180, 1988.
    3. Dental Products Panel of the Medical Devices Advisory 
Committee, meeting transcript, May 22, 2003.
    4. Dental Products Panel of the Medical Devices Advisory 
Committee, meeting transcript, August 8 and 9, 1995.
    5. Dental Products Panel of the Medical Devices Advisory 
Committee, information package, May 22, 2003.

List of Subjects in 21 CFR Part 872

    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 872 be amended in subpart D as follows:

PART 872--DENTAL DEVICES

    1. The authority citation for 21 CFR Part 872 continues to read as 
follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
    2. Section 872.3930 is revised to read as follows:


Sec.  872.3930   Bone grafting material.

    (a) Identification. Bone grafting material is a naturally or 
synthetically derived material, such as hydroxyapatite, tricalcium 
phosphate, demineralized bone additives, collagen, or polylactic acids, 
that is intended to fill, augment, or reconstruct periodontal or bony 
defects of the oral and maxillofacial region.
    (b) Classification. (1) Class II (special controls) if it contains 
no drug or biologic component. The special control for bone grafting 
materials that do not contain a drug or biologic component is FDA's 
``Class II Special Controls Guidance Document: Dental Bone Grafting 
Material.'' (See Sec.  872.1(e) for the availability of this guidance 
document.)
    (2) Class III (premarket approval) if it contains a drug or 
biologic component. Bone grafting materials that contain a drug or 
biologic component, such as biological response modifiers, require 
premarket approval.
    (c) Date PMA or notice of PDP is required. For devices described in 
paragraph (b)(2) of this section, no

[[Page 39380]]

effective date has been established for the requirement of premarket 
approval. (See Sec.  872.3).

    Dated: May 4, 2004.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 04-14767 Filed 6-29-04; 8:45 am]

BILLING CODE 4160-01-S