[Federal Register Volume 67, Number 26 (Thursday, February 7, 2002)]
[Proposed Rules]
[Pages 5753-5756]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-3017]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 888

[Docket No. 01N-0411]


Orthopedic Devices; Proposed Classification for the Resorbable 
Calcium Salt Bone Void Filler Device

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to 
classify the resorbable calcium salt bone void filler device intended 
to fill bony voids or gaps, caused by trauma or surgery, that are not 
intrinsic to the stability of the bony structure into class II (special 
controls). The agency is also publishing the recommendation of the 
Orthopedic and Rehabilitation Devices Panel (the Panel) regarding the 
classification of this device. After considering public comments on the 
proposed classification, FDA will publish a final regulation 
classifying this device. 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a draft guidance document that the agency proposes to use as a special 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 May 8, 2002. See 
section XIII of this document for the proposed effective date of a 
final rule based on this document.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Nadine Y. Sloan, Center for Devices 
and Radiological Health (HFZ-410), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-1296.

SUPPLEMENTARY INFORMATION:

I. 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 
(the SMDA) (Public Law 101-629) and the Food and Drug Administration 
Modernization Act of 1997 (FDAMA) (Public Law 105-115) 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 the 1976 amendments, class II devices were defined as 
those devices for which there is insufficient information to show that 
general controls themselves will ensure safety and effectiveness, but 
for which there is sufficient information to establish performance 
standards to provide such assurance.
    The SMDA broadened the definition of class II devices to mean those 
devices for which there is insufficient

[[Page 5754]]

information to show that general controls themselves will assure safety 
and effectiveness, but for which there is sufficient information to 
establish special controls to provide such assurance. Special controls 
may include performance standards, postmarket surveillance, patient 
registries, development and dissemination of guidelines, 
recommendations, and any other appropriate actions the agency deems 
necessary (section 513(a)(1)(B) of the act).
    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 met the following three requirements: (1) 
Received a recommendation from a device classification Panel (an FDA 
advisory committee); (2) published the Panel's 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 (21 U.S.C. 360c(f)) 
into class III without any FDA rulemaking process. Those devices remain 
in class III and require premarket approval, unless and until: (1) The 
device is reclassified into class I or II; (2) FDA issues an order 
classifying the device into class I or II in accordance with section 
513(f)(2) of the act as amended by FDAMA; or (3) FDA issues an order 
finding the device to be substantially equivalent, in accordance with 
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 previously offered 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. A preamendments device that has 
been classified into class III may be marketed, by premarket 
notification, 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.
    In 1987, when other orthopedic devices were classified (52 FR 33686 
at 33702, September 4, 1987), FDA was not aware that the calcium 
sulfate bone void filler device, a resorbable bone void filler, 
intended for orthopedic use in filling bony voids or gaps not intrinsic 
to the stability of the bony structure, was a preamendment device and 
inadvertently omitted classifying it. On December 12, 1997, FDA 
received a Classification Proposal and Summary of Safety and 
Effectiveness Information for the OsteoSet\TM\ Calcium Sulfate Bone 
Void Filler from Wright Medical Technology, Inc., requesting that the 
device be classified into class II (Ref. 1). Consistent with the act 
and the regulations, FDA consulted with the Panel regarding the 
classification of this device.

II. Device Identification

    FDA is proposing the following device name and identification name 
based on the Panel's recommendation (Ref. 2) and the agency's review:
    A resorbable calcium salt bone void filler device is a resorbable 
implant intended to fill bony voids or gaps caused by trauma or surgery 
that are not intrinsic to the stability of the bony structure.
    FDA has broadened the classification name and identification of the 
resorbable calcium salt bone void filler device because of the 
similarity of the calcium sulfate bone void filler device to other 
resorbable calcium salt bone void filler devices.

III. Recommendation of the Panel

    During a public meeting on January 12 and 13, 1998, the Panel 
unanimously recommended that the calcium sulfate bone void filler 
device be classified into class II (Ref. 2). The Panel believed that 
classification in class II with the recommended special controls of FDA 
guidance documents and FDA recognized voluntary consensus standards 
would provide reasonable assurance of the safety and effectiveness of 
the device.

IV. Summary of the Reasons for the Recommendation

    The Panel believed that the calcium sulfate bone void filler 
device, a resorbable calcium salt bone void filler device, should be 
classified 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. Because FDA 
believes that the safety and effectiveness of bone void filler devices 
composed of other resorbable calcium salts may also be assured through 
special controls, in addition to general controls, the agency has 
broadened the device name to resorbable calcium salt bone void filler 
device to include bone void filler devices made of other resorbable 
calcium salts.

V. Summary of the Data Upon Which the Recommendation is Based

    The Panel based its recommendation on the information contained in 
the petition, the information provided by FDA, and their personal 
knowledge of the device. In addition to information concerning the 
potential risks to health associated with the use of the resorbable 
calcium salt bone void filler device described in section VI of this 
document, there is reasonable knowledge of the benefits of the device. 
Specifically, the device provides an alternative treatment to use of 
either autogenous bone grafts, without the potential adverse effects of 
pain and morbidity associated with a bone harvest procedure, or use of 
allogeneic bone grafts, without the potential risk of disease 
transmission, including virus transmission. The device is also more 
readily and plentifully available than both alternative treatments.

VI. Risks to Health

    After considering the information in the petition, the Panel's 
deliberations, as well as the published literature and medical device 
reports (MDRs), FDA has evaluated the risks to health associated with 
the use of the resorbable calcium salt bone void filler device. There 
were no MDRs for the OsteoSet\TM\ calcium sulfate bone void filler, nor 
were there any MDRs for any other preamendments resorbable calcium 
sulfate bone void filler or postamendments resorbable calcium salt bone 
void filler. FDA now believes that the following are risks to health 
associated with use of the device: Infection of the soft tissue and/or 
bone (osteomyelitis) and fever; adverse tissue reaction; transient 
hypercalcemia; incomplete bone ingrowth, delayed union, and nonunion; 
fracture of the newly formed bone; and disease transmission and 
undesirable immune response associated with use of a biological source 
device material.

A. Infection of the Soft Tissue and/or Bone (Osteomyelitis) and Fever

    Infection of the soft tissue and/or bone (osteomyelitis) and fever 
are potential risks to health associated with all surgical procedures 
and implanted orthopedic devices (Ref. 1). Improper or impure material 
composition may irritate the wound and exacerbate a preexisting 
infection and improper sterilization or packaging may increase the risk 
of infection. Use of a device that

[[Page 5755]]

is not pyrogen-free may elicit a fever response.

B. Adverse Tissue Reaction

    Adverse tissue reaction is a potential risk to health associated 
with all implanted devices (Ref. 1). The use of this device in a wound 
will elicit a mild acute inflammatory reaction typical of a normal 
foreign body response. Inappropriate or impure device material 
composition may increase the severity of a local tissue reaction or may 
cause a systemic tissue reaction. Also, for a device intended to set in 
vivo, inappropriate device material composition may result in a 
significantly more exothermic setting reaction that may cause tissue 
necrosis.

C. Transient Hypercalcemia

    Inappropriate material composition may lead to substantially more 
rapid resorption of the implant, which may contribute to, or may cause, 
transient hypercalcemia. For patients receiving resorbable calcium 
sulfate bone void filler, transient hypercalcemia usually resolves 
without any adverse clinical sequelae (Ref. 1). Implanting the 
resorbable calcium salt bone void filler device in a patient with a 
preexisting calcium metabolism disorder (e.g., hypercalcemia) may lead 
to elevated, unsafe, transient hypercalcemia.

D. Incomplete Bone Ingrowth, Delayed Union, and Nonunion

    Incomplete bone growth into the treated void or gap, delayed union, 
and nonunion are potential risks to health that may require further 
surgical treatment. Device-related factors that may contribute to these 
risks are an improper material composition that resorbs too quickly or 
too slowly, or causes an infection or a severe local tissue reaction. 
Other factors, not related to the device, which may also contribute to 
incomplete ingrowth of new bone include inadequate preparation of the 
osseous defect and improper placement of the device.

E. Fracture of the Newly Formed Bone

    Formation of new bone that is not as strong as the host bone may 
occur, and may result in fracture of the bone that may require further 
surgical treatment.

F. Disease Transmission and Undesirable Immune Response Associated With 
Use of a Device Material Derived From a Biological Source

    Disease transmission, including virus transmission, and an 
undesirable immune response may occur if a calcium salt or calcium salt 
additive derived from a biological source, e.g., either animal or human 
tissue, is used that has not been adequately deproteinated or 
immunologically inactivated.

VII. Special Controls

    FDA believes that the class II special control draft guidance 
document entitled ``Class II Special Controls Guidance Document: 
Resorbable Calcium Salt Bone Void Filler Device,'' in addition to 
general controls, is adequate to control the identified risks to health 
associated with use of the resorbable calcium salt bone void filler 
device. FDA agrees with the Panel that FDA guidance documents and 
voluntary consensus standards are appropriate special controls to 
reasonably assure the safety and effectiveness of the device. FDA 
believes that the class II special controls draft guidance document, 
which incorporates FDA guidance documents, voluntary consensus 
standards, material characterization, performance testing, and 
instructions for use, addresses the Panel's recommendation for a 
guidance document and voluntary consensus standard special controls.
    The class II special controls draft guidance document addresses the 
risks to health associated with the resorbable calcium salt bone void 
filler device in the following five ways: (1) Adherence to the FDA 
guidance documents will assure that the device is safe for long-term 
implantation, control the risk of infection by assuring that only a 
sterile device is implanted, minimize the additional risk of eliciting 
a fever response, and assure that only a biocompatible material is 
used; (2) adherence to the voluntary consensus standards in the 
guidance document will assure that the device material has an 
appropriate composition and purity; (3) adherence to the material 
characterization recommendation will assure that the device has 
appropriate material properties for bone ingrowth and device 
resorption; (4) adherence to the performance testing recommendation 
will assure that implantation of the material provides an adequate 
environment for bony ingrowth and has the intended dissolution 
properties. For a calcium salt intended to set in vivo, it will also 
assure that the device material has an appropriate composition so that 
the setting reaction is not significantly exothermic to cause tissue 
necrosis. It will also assure that the device material has an 
appropriate composition to achieve the intended bone formation and 
material resorption, and that the newly formed bone is sufficiently 
strong. Finally, adherence to this section will help control the risks 
of disease transmission, including virus transmission, and undesirable 
immune response associated with implantation of a calcium salt or 
calcium salt additive derived from a biological source, e.g., either 
animal or human bone that has been inadequately deproteinated or 
immunologically inactivated; and (5) adherence to the instructions for 
use will help control the risk of an elevated, unsafe, transient 
hypercalcemia in patients with a preexisting calcium metabolism 
disorder.

VIII. Proposed Classification

    Based on the available information, FDA believes that the 
resorbable calcium salt bone void filler device should be classified 
into class II because special controls, in addition to general 
controls, would provide reasonable assurance of the safety and 
effectiveness of the device with the identified risks to health 
associated with the use of the device, and there is sufficient 
information to establish special controls to provide such assurance.

IX. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) that this 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.

X. 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) (as 
amended by subtitle D of the Small Business Regulatory Fairness Act of 
1996 (Public Law 104-121)), 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 consistent 
with the regulatory philosophy and principles identified in the 
Executive order. In addition, the proposed rule is not a significant 
regulatory action as defined by the Executive order and so is not 
subject to review under the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory

[[Page 5756]]

options that would minimize any significant impact of a rule on small 
entities. As unclassified devices, these devices are already subject to 
general controls such as premarket notification. The premarket 
notification guidance document will not substantially change the way in 
which these devices are regulated. The agency therefore certifies that 
this proposed rule, if issued, will not have a significant economic 
impact on a substantial number of small entities. In addition, this 
proposed rule 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.

XI. Paperwork Reduction Act of 1995

    This proposed rule does not contain information collection 
provisions that are subject to review by the Office of Management and 
Budget under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

XII. Submission of Comments

    Interested persons may submit to the Dockets Management Branch 
(address above) written or electronic comments regarding this proposal 
by May 8, 2002. Two copies of any comments are to be submitted, except 
that individuals may submit one 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 Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

XIII. Proposed Dates

    FDA proposes that any final regulation based on this proposal 
become effective 30 days after its publication in the Federal Register.

XIV. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Wright Medical Technology, Inc., Arlington, TN, 
Classification Proposal and Summary of Safety and Effectiveness 
Information for the OsteoSet\TM\ Calcium Sulfate Bone Void Filler, 
received December 12, 1997.
    2. Transcript of the Orthopedic and Rehabilitation Devices Panel 
meeting, January 12 and 13, 1998, pp. 1-10 and 299-372.

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 888.3045 is added to subpart D to read as follows:


Sec. 888.3045  Resorbable calcium salt bone void filler device.

    (a) Identification. A resorbable calcium salt bone void filler 
device is a resorbable implant intended to fill bony voids or gaps, 
caused by trauma or surgery, that are not intrinsic to the stability of 
the bony structure.
    (b) Classification. Class II (special controls). The special 
control for this device is the FDA guidance document entitled ``Class 
II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler 
Device.''

    Dated: October 5, 2001.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 02-3017 Filed 2-6-02; 8:45 am]
BILLING CODE 4160-01-S