[Federal Register: January 17, 2007 (Volume 72, Number 10)]
[Proposed Rules]
[Page 1951-1954]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17ja07-15]
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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:
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 following 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 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