[Federal Register Volume 70, Number 81 (Thursday, April 28, 2005)]
[Rules and Regulations]
[Pages 21947-21950]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-8467]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 872

[Docket No. 2002P-0520] (formerly Docket No. 02P-0520)


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is reclassifying 
tricalcium phosphate (TCP) granules for dental bone repair from class 
III to class II (special controls), classifying into class II (special 
controls) other bone grafting material for dental indications, and 
revising the classification name and identification of the device type. 
Bone grafting materials that contain a drug that is a therapeutic 
biologic will remain in class III and continue to require a premarket 
approval application. The classification identification includes 
materials such as hydroxyapatite, tricalcium phosphate, polylactic and 
polyglycolic acids, or collagen. This action is being taken to 
establish sufficient regulatory controls that will provide reasonable 
assurance of the safety and effectiveness of these devices. Elsewhere 
in this issue of the Federal Register, FDA is announcing the 
availability of the guidance document that will serve as the special 
control for the class II devices.

EFFECTIVE DATE: May 31, 2005.

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: 
[email protected].

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

[[Page 21948]]

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 FDA, in response to a reclassification petition or on its 
own initiative, has classified the device into class I or II.

II. Regulatory History of the Device

    In the Federal Register of June 30, 2004 (69 FR 39377), FDA 
proposed to reclassify TCP granules for dental bone repair from class 
III to class II (special controls). Concurrently, FDA proposed to 
classify into class II (special controls) all other bone grafting 
material for dental indications, except those that contained a drug or 
biologic component; and to revise the classification name and 
identification of the device. In the proposed rule, FDA identified the 
device type as bone grafting material such as hydroxyapatite, 
tricalcium phosphate, demineralized bone additives, collagen, or 
polylactic acid intended to fill, augment, or reconstruct periodontal 
or bony defects of the oral and maxillofacial region.
    The SUPPLEMENTARY INFORMATION section of the June 30, 2004, 
proposed rule presented information on the classification 
recommendations of the Dental Products Advisory Panel (the panel), a 
summary of the reasons for the recommendations, a summary of the data 
upon which the recommendations were based, and an assessment of the 
device's risks to public health.
    Also in the Federal Register of June 30, 2004 (69 FR 39485), FDA 
announced the availability of the draft guidance document entitled 
``Class II Special Controls Guidance Document: Dental Bone Grafting 
Material'' that FDA intended to serve as the special control for TCP 
and other bone grafting materials, if FDA classified and reclassified 
this device type. FDA gave interested persons until September 28, 2004, 
to comment on the proposed regulation and special controls draft 
guidance document.

III. Analysis of the Comment and FDA's Response

    FDA received one comment on the proposed rule and guidance 
document. The comment said that TCP granules should remain in class III 
(premarket approval) and that all other bone grafting materials for 
dental indications should be regulated in class III because the 
commenter believed the special controls (composition, physical 
properties, and compliance with the American Society for Testing and 
Materials (ASTM) composition standards) described in the draft guidance 
document were not sufficient to provide a reasonable assurance of 
safety and effectiveness for these devices. The comment states that 
only evidence from clinical studies is sufficient to provide a 
reasonable assurance of safety and effectiveness for these devices.
    FDA disagrees in part with the comment. In most cases, FDA believes 
that there is sufficient human experience with the dental bone grafting 
material devices being reclassified and classified into class II to 
establish a special controls guidance to provide reasonable assurance 
of safety and effectiveness through the 510(k) process without the 
submission of clinical data. FDA has determined that this experience 
supports the conclusion that information on composition, physical 
properties, and compliance with ASTM composition standards in a 510(k) 
will provide adequate information for FDA review of the device, if 
there is no change in the formulation, design, technology, or 
indication for use of the device. In cases in which there is such a 
change, however, the special controls guidance clearly states that FDA 
recommends the submission of clinical data in the 510(k) to support a 
substantial equivalence determination. If the manufacturer cannot 
demonstrate that the new device is substantially equivalent, the device 
will be found not substantially equivalent and a premarket approval 
application may be required. This approach is consistent with the 
general recommendations of the panel in 1995 and in 2003. Therefore, 
FDA believes that special controls, in addition to general controls, 
will provide a reasonable assurance of the safety and effectiveness of 
these devices and these devices can be classified in class II. Bone 
grafting material devices that contain a drug that is a therapeutic 
biologic will remain in class III and continue to require a premarket 
approval application.

IV. Summary of Final Rule

    Therefore, under sections 513 and 520(l) of the act, FDA is 
adopting the summary of reasons for the panel's recommendation, the 
summary of data upon which the panel's recommendations are based, and 
the assessment of the risks to public health stated in the proposed 
rule published on June 30, 2004. Furthermore, FDA is issuing this final 
rule, Sec.  872.3930 (21 CFR 872.3930), that reclassifies TCP granules 
for dental bone repair from class III to class II (special controls); 
classifies into class II (special controls) other bone grafting 
material for dental indications; and revises the classification name 
and identification of the device. Bone grafting materials that contain 
a drug that is a therapeutic biologic will remain in class III and 
continue to require a premarket approval application.
    FDA is making the following changes to the identification of bone 
grafting material:
     Removing the phrase ``a naturally or synthetically 
derived'' because it does not apply to all the examples that follow.
     Removing ``demineralized bone additives.'' Minimally 
manipulated demineralized bone is regulated as human cells, tissues, 
and cellular and tissue-based products under section 361 of the Public 
Health Service Act (21 CFR 1271.10). Human demineralized bone with 
additives is regulated as a medical device and is subject to premarket 
notification procedures. FDA intends to publish a separate rule for 
human demineralized bone with additives to classify the device into 
class II and establish a special control.
     Adding ``polyglycolic'' to ``polylactic acids'' to more 
clearly identify these materials as a class of poly(alpha-hydroxy) 
acids because they are often supplied as a mixture.
     Clarifying that bone grafting materials that contain a 
drug that is a therapeutic biologic are the devices that will remain in 
class III. Therapeutic biologics are biological response modifiers, 
such as growth factors, cytokines, and certain monoclonal antibodies 
that are regulated as drugs. Because insufficient information exists to 
determine that general controls and special controls are sufficient to 
provide a reasonable assurance of their safety and effectiveness, these 
devices will remain in class III and continue to require premarket 
approval applications.
    FDA is also revising paragraph (c) in Sec.  872.3930 to clarify the 
status of the devices described in paragraph (b)(2) that contain a drug 
that is a therapeutic biologic. 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 (21 U.S.C. 360c(f)) into class III without 
any FDA rulemaking process. Those devices remain in class III and 
require a premarket approval application, unless and until the device 
is reclassified into class I or II or FDA

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issues an order finding the device to be substantially equivalent, 
under section 513(i) of the act (21 U.S.C. 360c(i)), 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 21 CFR part 807 of the regulations. FDA has 
previously found the devices described in paragraph (b)(2) to be 
postamendments devices and not substantially equivalent to devices that 
do not require premarket approval. Therefore, these devices are in 
class III by operation of the statute and require premarket approval. 
FDA has revised paragraph (c) to reflect this.
    This action is being taken to establish sufficient regulatory 
controls to provide reasonable assurance of the safety and 
effectiveness of the devices in class II. The guidance document 
entitled ``Class II Special Controls Guidance Document: Dental Bone 
Grafting Material Devices'' will serve as the special control for the 
device. Elsewhere in this issue of the Federal Register, FDA is 
announcing the availability of this guidance. Following the effective 
date of the final rule, any firm submitting a 510(k) premarket 
notification for this device will need to address the issues covered in 
the special controls guidance document. However, the firm need only 
show that its 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: Material 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 exempting 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.

V. Environmental Impact

    FDA has determined under 21 CFR 25.34(b) that this classification 
and reclassification action 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.

VI. Analysis of Impacts

    FDA has examined the impacts of the final 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, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this final rule is not a significant regulatory action under 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. FDA believes that manufacturers of the devices being 
reclassified or classified into class II are already substantially in 
compliance with the recommendations in the guidance document. Because 
manufacturers of the devices subject to the special control are being 
relieved of the burden of submitting a premarket approval application, 
the agency certifies that the final 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 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

VII. Federalism

    FDA has analyzed the final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies conferring 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, FDA has concluded that the 
rule does not contain policies that have federalism implications as 
defined in the Executive order. As a result, a federalism summary 
impact statement is not required.

VIII. Paperwork Reduction Act of 1995

    FDA concludes that the final rule contains no collections of 
information. Therefore, clearance by the Office of Management and 
Budget, according to the Paperwork Reduction Act of 1995 (44 U.S.C. 
3501-3520) is not required.

List of Subjects in 21 CFR Part 872

    Medical devices.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
872 is amended as follows:

PART 872--DENTAL DEVICES

0
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.

0
2. Section 872.3930 is revised to read as follows:


Sec.  872.3930   Bone grafting material.

    (a) Identification. Bone grafting material is a material such as 
hydroxyapatite, tricalcium phosphate, polylactic and polyglycolic 
acids, or collagen, 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) for bone 
grafting materials that do not contain a drug that is a therapeutic 
biologic. The special control is FDA's ``Class II Special Controls 
Guidance Document: Dental Bone Grafting Material Devices.'' (See Sec.  
872.1(e) for the availability of this guidance document.)
    (2) Class III (premarket approval) for bone grafting materials that 
contain a drug that is a therapeutic biologic. Bone grafting materials 
that contain a drug that is a therapeutic biologic, such as biological 
response modifiers, 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

[[Page 21950]]

this section shall have an approved PMA or a declared completed PDP in 
effect before being placed in commercial distribution.

    Dated: April 4, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 05-8467 Filed 4-27-05; 8:45 am]
BILLING CODE 4160-01-S