[Federal Register Volume 72, Number 10 (Wednesday, January 17, 2007)]
[Proposed Rules]
[Pages 1951-1954]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-476]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 888

[Docket No. 2005P-0121]


Orthopedic Devices; Reclassification of Non-Invasive Bone Growth 
Stimulator

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of panel recommendation.

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SUMMARY: The Food and Drug Administration (FDA) is issuing for public 
comment the recommendation of the Orthopaedic and Rehabilitation 
Devices Panel to deny a petition to reclassify the non-invasive bone 
growth stimulator from class III to class II. The Panel made this 
recommendation after reviewing the reclassification petition submitted 
by RS Medical Corp., as well as consideration of presentations made at 
the Panel meeting by the petitioner, FDA, and members of the public. 
FDA is also issuing for public comment its findings on the Panel's 
recommendation. After considering any public comments on the Panel's 
recommendation and FDA's findings, FDA will approve or deny the 
reclassification petition by order in the form of a letter to the 
petitioner. FDA's decision on the reclassification petition will be 
announced in the Federal Register.

DATES: Submit written or electronic comments by April 17, 2007.

ADDRESSES: You may submit comments, identified by Docket No. 2005P-
0121, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
    <bullet> 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 following ways:
    <bullet> FAX: 301-827-6870.
    <bullet> 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 No. 2005P-0121 for this notice. 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(s), 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: Michel Janda, Center for Devices and 
Radiological Health (HFZ-410), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 240-276-3600.

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 (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 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: (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 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 of the 
regulations (21 CFR part 807).
    Reclassification of classified postamendments devices is governed 
by section 513(f)(3) 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

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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 petition to a device classification panel. 
The Panel shall make a recommendation to the Secretary respecting 
approval or denial of the petition. Any such recommendation shall 
contain (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 petition was filed.

II. Regulatory History of the Device

    In accordance with section 513(f)(1) of the act, the non-invasive 
bone growth stimulators were automatically classified into class III 
because they were not introduced or delivered for introduction into 
interstate commerce for commercial distribution before May 28, 1976, 
and have not been found substantially equivalent to a device placed in 
commercial distribution after May 28, 1976, which was subsequently 
classified or reclassified into class II or class I. Therefore, the 
device can not be placed in commercial distribution unless it is 
reclassified under section 513(f)(3), or subject to an approved 
premarket approval application (PMA) under section 515 of the act (21 
U.S.C. 360e).
    In a petition dated February 7, 2005, that was received by FDA on 
February 9, 2005, RS Medical Corp. requested that FDA reclassify the 
non-invasive bone growth stimulator from class III to class II. (Ref. 
1) The petition was submitted under section 513(e) of the act but FDA 
is reviewing the petition under section 513(f)(3) of the act because 
that section contains the appropriate procedures for reclassification 
of postamendments devices. FDA requested additional information and the 
petitioner amended the petition on August 1, 2005. In accordance with 
the act and the regulations, FDA referred the petition as amended to an 
FDA Advisory Committee, the Orthopedic and Rehabilitation Devices Panel 
(the Panel) for its recommendations on the requested reclassification.

III. Description of Device Proposed for Reclassification

    The Petitioner identified the device as follows:
    A non-invasive bone growth stimulator is a device that provides 
stimulation through electrical and/or magnetic fields to facilitate the 
healing of nonunion fractures and lumbar spinal fusions. The 
stimulation may be delivered through capacitive coupling (CC) with 
electrodes placed directly over the treatment site or through pulsed 
electromagnetic fields (PEMF) with treatment coils placed into a brace 
or over a cast at the treatment site. The device is intended for use: 
(1) For the treatment of established nonunion fractures acquired 
secondary to trauma (excluding vertebrae and flat bone), and (2) as an 
adjunct to the treatment of lumbar spinal fusion surgery for one or two 
levels. The device consists of an output waveform generator, either 
battery-powered or AC-powered; a user interface with visual and/or 
audible alarms; and electrodes or coils to deliver the stimulation.

IV. Recommendations of the Panel

    On June 2, 2006, the Panel deliberated on information in RS 
Medical's petition; the presentations made by RS Medical, FDA, and 
members of the public; and their own experience with non-invasive bone 
growth stimulators (Ref. 2). The Panel voted four to two to recommend 
that non-invasive bone growth stimulators be retained in class III.

V. Risks to Health

    The Panel identified the following risks to health associated with 
the non-invasive bone growth stimulator:

A. Electric Shock

    A patient or health care professional could be shocked from the use 
and operation of the device via an AC line voltage exposure during 
charging, circuitry malfunction, connection/disconnection of electrodes 
or coils, control circuit failure, damaged channel jacks, defective 
electrodes/coil delivering inappropriate output, faulty lead wires, 
inappropriate output, poor connection between electrodes/coils and lead 
wires, poor solder on circuit board, reposition of electrodes/coils 
during treatment, and use of AC current source during treatment.

B. Burn

    A patient or health care professional could be burned from the use 
and operation of the device via an AC line voltage exposure during 
charging, connection/disconnection of the electrodes/coils or control 
unit while receiving treatment, defective electrodes/coil delivering 
inappropriate output, incorrect electrode/coil size or alteration, 
inappropriate output, use of AC current source for treatment, and use 
of control unit and battery charger while sleeping.

C. Skin Irritation and/or Allergic Reaction

    A patient could experience skin irritation and/or allergic reaction 
associated with the use and operation of the device via the use of non-
biocompatible device materials and/or non-biocompatible electrode gel.

D. Inconsistent or Ineffective Treatment

    A patient could receive inconsistent or ineffective treatment via 
battery deterioration, control circuit failure, defective electrode/
coils, device damage from dropping or bumping, device short circuits, 
driver circuit failure, electromagnetic interference (EMI) or radio 
frequency interference (RFI), failure to follow prescribed use, 
hardware failure, improper position of electrodes/coil, inappropriate 
output, incorrect battery/battery charger, ineffective output, low 
battery voltage, poor interface between electrodes/coil and patient, 
and switch failure.

E. Adverse Interaction with Electrical Implants

    A patient with electrically-powered implants (such as cardiac 
pacemakers, cardiac defibrillators, and neuro-stimulators) could 
experience an adverse interaction with an implanted electrical device 
via EMI or RFI.

F. Internal/External Fixation Devices

    A patient with internal or external fixation devices could receive 
inconsistent or ineffective treatment due to interaction of the device 
with the metallic fixation devices via interference with treatment 
field through magnetic field interaction and/or electrical inductance 
within metallic device.

G. Biological Risks: Carcinogenicity, Genotoxicity, Mutagenicity, and 
Teratology

    A patient may experience adverse biologic affects resulting from 
prolonged exposure to the treatment signal via biologic interaction 
with the treatment signal at a cellular level.

VI. Summary of Reasons for Recommendation

    The Panel believes that the non-invasive bone growth stimulator 
should be retained in class III because there is insufficient 
information in this petition

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to establish that special controls in association with general controls 
would provide a reasonable assurance of the safety and effectiveness of 
the device.

VII. Summary of Data Upon Which the Panel Recommendation is Based

    The petitioner provided the following information:

A. Reports on Non-Unions

    The petitioner submitted 35 articles (5 describing capacitive 
coupling devices and 30 describing the use of pulsed electromagnetic 
field devices) reporting outcomes for over 5,600 patients. According to 
the petitioner, these studies indicate the device's ability to promote 
osteogenesis in patients with an established non-union, which may 
include previously failed surgical attempts to establish union.

B. Reports on Adjunctive Lumbar Spinal Fusion

    The petitioner has submitted eight articles (one utilizing 
capacitive coupling devices and seven utilizing pulsed electromagnetic 
field devices) reporting outcomes for over 1,100 patients. According to 
the petitioner, these studies indicate the device's ability to promote 
osteogenesis in patients as an adjunct to the treatment of lumbar 
spinal fusion for one or two levels.

C. Reports on Preclinical Findings

    The petitioner has cited 21 articles in the petition amendment 
describing studies in animal models. The animal studies described in 
the petition amendment were designed to evaluate new signals, dose/
response relationships, and the potential pathways of bone repair 
processes. In addition, 14 articles were presented that describe 
studies in cell culture systems designed to examine the mechanism(s) of 
action of various electrical stimuli in bone. These studies, conducted 
at the cellular level, were intended to investigate the sequence of 
events that occur as a result of electrical stimulation, the 
interaction of the fields at the level of the cell membrane with regard 
to ion channels and receptor interaction, and signal transduction; and 
to identify cell types that do or do not respond to electrical 
stimulation.
    The Panel recommended that the proposed special controls (Ref 1.) 
were sufficient to control for the risk of electric shock, burn, skin 
irritation, and/or allergic reaction; adverse interaction with 
electrical implants; adverse interaction with internal/external 
fixation devices; and biological risks (carcinogenicity, genotoxicity, 
mutagenicity and teratology). However, the Panel believed that there 
was insufficient evidence presented by the petitioner to control for 
the risk of inconsistent or ineffective treatment because there is a 
lack of knowledge about how waveform characteristics (e.g., pulse 
duration, amplitude, power, frequency) affect the clinical response to 
treatment. This concern was also expressed by the Panel regarding 
potential modifications made to the device. It is not known how a 
change to the device output due to device modifications may impact the 
clinical response to treatment. The Panel requested additional clinical 
data and/or special controls to control for the risk of inconsistent or 
ineffective treatment that may occur as the result of device 
modifications (Ref. 2).

VIII. FDA's Findings

    FDA believes that certain device modifications are unlikely to 
adversely affect device safety and effectiveness and such changes could 
be adequately validated using bench-top testing. However, FDA also 
believes that there was not adequate evidence in the petition to 
establish that the petitioner's proposed special controls could be used 
to adequately mitigate the risk of inconsistent or ineffective 
treatment. Additional evidence is required to establish special 
controls, including preclinical test methods, to mitigate the risk of 
inconsistent or ineffective treatment.
    Because FDA has concerns about the ability of the petitioner's 
proposed special controls to control the risk of inconsistent and 
ineffective treatment, FDA is unable to conclude that general controls 
and the petitioner's proposed special controls would provide a 
reasonable assurance of safety and effectiveness for this device type. 
Therefore, based on the currently available information, FDA concurs 
with the Panel's recommendation to retain the non-invasive bone growth 
stimulator as a class III device.

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 this notice 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 reclassification petition denial, if finalized, 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. If FDA accepts the Panel recommendation and denies 
the petition for reclassification, the regulatory status of the device 
will remain the same as it is now. Because this action, if finalized, 
will maintain the status quo, the agency certifies that the 
reclassification petition denial 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 $122 million, using the most current (2005) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
reclassification petition action to result in any 1-year expenditure 
that would meet or exceed this amount.

XI. Federalism

    FDA has analyzed this action in accordance with the principles set 
forth in Executive Order 13132. FDA has determined that the action, 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 concludes that the action 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.

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XII. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this notice. 
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.

XIII. 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. Reclassification petition from RS Medical Corp., dated 
February 7, 2005, and amendment dated November 30, 2005.
    2. Orthopedic and Rehabilitation Devices Panel Meeting 
Transcript, June 2, 2006.

    Dated: January 5, 2007.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. E7-476 Filed 1-16-07; 8:45 am]
BILLING CODE 4160-01-S