Physical Medicine Devices; Reclassification of Non-Invasive Bone Growth Stimulators, 49986-49994 [2020-17543]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 85, Number 159 (Monday, August 17, 2020)]
[Proposed Rules]
[Pages 49986-49994]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-17543]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 890

[Docket No. FDA-2020-N-1053]


Physical Medicine Devices; Reclassification of Non-Invasive Bone 
Growth Stimulators

AGENCY: Food and Drug Administration, Health and Human Services (HHS).

ACTION: Proposed amendment; proposed order; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
reclassify non-invasive bone growth stimulators, postamendments class 
III devices (product codes LOF and LPQ), into class II (special 
controls), subject to premarket notification. FDA is also proposing a 
new device classification with the name ``non-invasive bone growth 
stimulators'' along with the proposed special controls that the Agency 
believes are necessary to provide a reasonable assurance of safety and 
effectiveness of these devices. FDA is proposing this reclassification 
on its own initiative. If finalized, this order will reclassify these 
devices from class III (premarket approval) to class II (special 
controls) and reduce the regulatory burdens associated with these 
devices, as these devices will no longer be required to submit a 
premarket approval application (PMA), but are subject to premarket 
notification (510(k)) requirements and general and special controls.

DATES: Submit either electronic or written comments on the proposed 
order by October 16, 2020. Please see section XII of this document for 
the proposed effective date when the new requirements apply and for the 
proposed effective date of a final order based on this proposed order.

ADDRESSES: You may submit comments as follows. Please note that late,

[[Page 49987]]

untimely filed comments will not be considered. Electronic comments 
must be submitted on or before October 16, 2020. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of October 16, 2020. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal Rulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2020-N-1053 for ``Physical Medicine Devices; Reclassification of 
Non-Invasive Bone Growth Stimulators.'' Received comments, those filed 
in a timely manner (see ADDRESSES), will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at https://www.regulations.gov or at the Dockets Management 
Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Jesse Muir, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4508, Silver Spring, MD 20993, 240-402-6679, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended, 
establishes a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the FD&C Act (21 U.S.C. 
360c) established three categories (classes) of devices, reflecting 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 (general controls and special controls), 
and class III (general controls and premarket approval).
    Devices that were not in commercial distribution prior to May 28, 
1976 (generally referred to as postamendments devices) are 
automatically classified by section 513(f)(1) of the FD&C Act into 
class III without any FDA rulemaking process. Those devices remain in 
class III and require premarket approval unless, and until: (1) FDA 
reclassifies the device into class I or II or (2) FDA issues an order 
finding the device to be substantially equivalent, in accordance with 
section 513(i) of the FD&C Act, to a predicate device that does not 
require premarket approval. FDA determines whether new devices are 
substantially equivalent to predicate devices by means of premarket 
notification procedures in section 510(k) of the FD&C Act (21 U.S.C. 
360(k)) and part 807 (21 CFR part 807), subpart E, of the regulations.
    A postamendments device that has been initially classified in class 
III under section 513(f)(1) of the FD&C Act may be reclassified into 
class I or class II under section 513(f)(3) of the FD&C Act. Section 
513(f)(3) of the FD&C Act provides that FDA acting by administrative 
order, can reclassify the device into class I or class II on its own 
initiative, or in response to a petition from the manufacturer or 
importer of the device. To change the classification of the device, the 
proposed new class must have sufficient regulatory controls to provide 
reasonable assurance of the safety and effectiveness of the device for 
its intended use.
    Reevaluation of the data previously presented before the Agency is 
an appropriate basis for subsequent action, where the reevaluation is 
made in light of newly available regulatory authority (see Bell v. 
Goddard, 366 F.2d 177, 181 (7th Cir. 1966); Ethicon, Inc. v. FDA, 762 
F. Supp. 382, 388-391 (D.D.C. 1991)) or in light of changes in 
``medical science'' (Upjohn v. Finch, 422 F.2d 944, 951 (6th Cir. 
1970)). Whether data before the Agency are old or new, the ``new 
information'' to support reclassification under 513(f)(3) must be 
``valid scientific evidence'', as defined in section 513(a)(3) of the 
FD&C Act and Sec.  860.7(c)(2) (21 CFR 860.7(c)(2)). (See, e.g., 
General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens 
Assoc. v. FDA, 766 F.2d 592 (D.C. Cir.

[[Page 49988]]

1985), cert. denied, 474 U.S. 1062 (1986).)
    FDA relies upon ``valid scientific evidence,'' as defined in 
section 513(a)(3) of the FD&C Act and Sec.  860.7(c)(2), in the 
classification process to determine the level of regulation for 
devices. To be considered in the reclassification process, the ``valid 
scientific evidence'' upon which the Agency relies must be publicly 
available. Publicly available information excludes trade secret and/or 
confidential commercial information, e.g., the contents of a pending 
PMA (see section 520(c) of the FD&C Act (21 U.S.C. 360j(c)). Section 
520(h)(4) of the FD&C Act provides that FDA may use, for 
reclassification of a device, certain information in a PMA 6 years 
after the application has been approved (Ref. 1). This includes 
information from clinical and preclinical tests or studies that 
demonstrate the safety or effectiveness of the device, but does not 
include descriptions of methods of manufacture or product composition 
and other trade secrets.
    In accordance with section 513(f)(3) of the FD&C Act, FDA is 
issuing this proposed order to reclassify non-invasive bone growth 
stimulator devices, postamendments class III devices, into class II 
(special controls), subject to premarket notification because FDA 
believes the standard in section 513(a)(1)(B) of the FD&C Act is met as 
there is sufficient information to establish special controls, which in 
addition to general controls, will provide reasonable assurance of the 
safety and effectiveness of the device.\1\
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    \1\ In December 2019, FDA began adding the term ``Proposed 
amendment'' to the ``ACTION'' caption for these documents, typically 
styled ``Proposed order'', to indicate that they ``propose to 
amend'' the Code of Federal Regulations. This editorial change was 
made in accordance with the Office of Federal Register's (OFR) 
interpretations of the Federal Register Act (44 U.S.C. chapter 15), 
its implementing regulations (1 CFR 5.9 and parts 21 and 22), and 
the Document Drafting Handbook.
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    Section 510(m) of the FD&C Act provides that a class II device may 
be exempted from the premarket notification requirements under section 
510(k) of the FD&C Act, if the Agency determines that premarket 
notification is not necessary to reasonably assure the safety and 
effectiveness of the device. FDA has determined that premarket 
notification is necessary to reasonably assure the safety and 
effectiveness of non-invasive bone growth stimulator devices. 
Therefore, the Agency does not intend to exempt these proposed class II 
devices from premarket notification (510(k)) submission as provided 
under section 510(m) of the FD&C Act.

II. Regulatory History of Non-Invasive Bone Growth Stimulator Devices

    In accordance with section 513(f)(1) of the FD&C Act, non-invasive 
bone growth stimulator devices 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 is subject to PMA requirements under section 515 of the FD&C Act 
(21 U.S.C. 360e).
    Accordingly, on November 6, 1979, FDA approved a PMA for the Bio 
Osteogen System 204 (P790002) (Ref. 2). Since that time, five 
additional original PMAs have been approved for non-invasive bone 
growth stimulators (P850007, P850022, P900009, P910066, and P030034). 
On February 9, 2005, FDA received a reclassification petition dated 
February 7, 2005, submitted by RS Medical Corporation, requesting that 
FDA reclassify certain non-invasive bone growth stimulators from class 
III to class II (Ref. 3). As stated in the Notice of Panel 
Recommendation discussed further below, ``the petition was submitted 
under section 513(e) of the act but FDA . . . review[ed] the petition 
under section 513(f)(3) of the act because that section contain[ed] the 
appropriate procedures for reclassification of postamendments devices'' 
(72 FR 1951 at 1952, January 17, 2007). FDA requested additional 
information and the petitioner amended the petition on November 30, 
2005 (``amended petition''). In accordance with the FD&C Act and 
regulations, FDA referred the petition, as amended, to the FDA Advisory 
Committee, specifically the Orthopaedic and Rehabilitation Devices 
Panel (``the 2006 Panel'') for its recommendations on the requested 
reclassification.
    On June 2, 2006, the 2006 Panel deliberated on the information in 
RS Medical's petition; the presentations made by RS Medical, FDA, and 
members of the public; and their own experience with certain non-
invasive bone growth stimulators (Ref. 4).
    The 2006 Panel identified the following risks to health associated 
with non-invasive bone growth stimulators: Electric shock; burn; skin 
irritation and/or allergic reaction; inconsistent or ineffective 
treatment; adverse interaction with electrical implants; adverse 
interactions with internal/external fixation devices; and biological 
risks. The 2006 Panel did not specifically address risks associated 
with ultrasound-based devices, as these were outside the scope of RS 
Medical's petition; however, as discussed below, based upon FDA's 
review of information since the Panel meeting, the risks identified 
with ultrasound-based devices, along with their reported benefits, are 
comparable to those of non-invasive bone growth stimulators 
incorporating other modalities.
    The majority of the 2006 Panel recommended that non-invasive bone 
growth stimulators should be retained in class III because there was 
insufficient information in the petition by RS Medical to establish 
that special controls in conjunction with general controls would 
provide a reasonable assurance of the safety and effectiveness of the 
device. Specifically, the Panel recommended that the proposed special 
controls by RS Medical were sufficient to control for the risk of 
electric shock, burn, skin irritation, and/or allergic reaction; 
adverse interaction with electrical implants; adverse interactions with 
internal/external fixation devices; and biological risks. However, the 
Panel believed that there was insufficient evidence presented by RS 
Medical 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), 
including potential modifications to the device, affect the clinical 
response to treatment. The Panel requested additional clinical data 
and/or special controls, which was not adequately devised by the 
petitioner, to control for the risk of inconsistent or ineffective 
treatment.
    FDA concurred with the 2006 Panel's recommendation, and similarly 
believed that RS Medical's petition was inadequate in that FDA had 
concerns about the petitioner's proposed special controls to control 
the risk of inconsistent or ineffective treatment. In the Federal 
Register of January 17, 2007 (72 FR 1951), FDA published a Notice of 
Panel Recommendations (``the 2007 Notice''), as referenced above.
    In a letter dated April 2, 2007, RS Medical requested that its 
petition be withdrawn (Ref. 5). On July 10, 2007, FDA granted RS 
Medical's request for withdrawal of the petition and did not take any 
further action on the petition (Ref. 6). FDA has not received any 
subsequent petition requesting reclassification of these devices.
    Subsequently, as part of the Center for Devices and Radiological 
Health's 2014-2015 strategic priority, ``Strike the Right Balance 
Between Premarket and Postmarket Data Collection,'' a

[[Page 49989]]

retrospective review of all PMA product codes with active PMAs approved 
prior to 2010 was conducted to determine whether, based on our current 
understanding of the technology, certain devices could be reclassified 
(down-classified). On April 29, 2015, FDA published a document in the 
Federal Register identifying certain product codes as potential 
candidates for reclassification (80 FR 23798), including non-invasive 
bone growth stimulators under product codes LOF and LPQ, from class III 
to class II (Ref. 7). One comment was received in response to this 
proposal for reclassification of LOF and LPQ; this comment did not 
support FDA's intention to reclassify these devices, citing the 
concerns discussed during the 2006 Panel. This comment was considered 
in development of this proposed order. Note that invasive bone growth 
stimulators, designated under product code LOE, are outside the scope 
of this proposed reclassification. As noted in the 2006 Panel, invasive 
bone growth stimulator devices have added risks compared to non-
invasive bone growth stimulators, and therefore would require a 
separate classification discussion. Furthermore, invasive bone growth 
stimulators were also considered as a part of the aforementioned PMA 
retrospective review and FDA determined that these devices should 
remain as class III (Ref. 8). Therefore, FDA will continue to regulate 
invasive bone growth stimulators as a class III device, subject to PMA 
requirements.
    While RS Medical's petition inadequately addressed all of the risks 
associated with non-invasive bone growth stimulators for 
reclassification, FDA is, on its own initiative, proposing to 
reclassify these devices from class III to class II, and believes that 
sufficient information exists to establish special controls, as 
identified in this proposed order, that, together with general 
controls, can provide a reasonable assurance of safety and 
effectiveness for this device type. Additionally, RS Medical in its 
petition excluded use of these devices as an adjunct to cervical fusion 
surgery in patients at high risk for nonfusion, as well as for use in 
congenital pseudarthrosis. Based upon the review of the evidence and 
FDA's ability to establish special controls, FDA believes these 
indications that have been approved for currently marketed non-invasive 
bone growth stimulator devices should be included in this proposed 
reclassification.

III. Device Description

    Non-invasive bone growth simulators, currently designated under 
product codes LOF and LPQ, are typically composed of a waveform 
generator and transducer (e.g., coils, electrodes, and/or ultrasound 
transducers). Patient-contacting surfaces include the transducers, lead 
wires, and the device outer casing.
    Non-invasive bone growth stimulators utilize an electrical 
component to produce an output electrical, magnetic, or ultrasonic 
waveform that is delivered to a treatment site via a non-invasively 
applied transducer (e.g., electromagnetic coil or ultrasound 
transducer) or electrodes (e.g., capacitor plates). The device also 
incorporates an internal means to monitor the output waveform and 
delivery of treatment, and to provide visual and/or audible alarms to 
alert the user of improper device function. The induced electrical and/
or magnetic fields are generated using one of the following modalities:
     Capacitive coupling (CC), in which a pair of electrodes 
are placed on the skin such that a current can be driven across the 
target site;
     pulsed electromagnetic fields (PEMF), in which a modulated 
electromagnetic field is generated near the treatment site though an 
external coil; or
     combined magnetic fields (CMF), in which a coil generates 
a combination of a static and pulsed magnetic field near the treatment 
site.
    The ultrasonic waveform is generated using:
     Low intensity pulsed ultrasound (LIPUS), in which pulsed 
ultrasonic signals are generated using ultrasonic transducers.
    The non-invasive nature of the device obviates the need for sterile 
components; however, patient-contacting surfaces should be capable of 
being cleaned as needed and biocompatibility must be ensured.
    Non-invasive bone growth stimulators are generally intended to 
promote osteogenesis as adjunct to primary treatments for fracture 
fixation or spinal fusion. The indications for use for this device type 
depend on the specific device characteristics, but have included:
     Treatment of an established non-union secondary to trauma 
of the appendicular system,
     treatment of congenital pseudarthrosis,
     treatment of failed fusions of the appendicular system,
     early treatment of certain fresh fractures, and
     as an adjunct to lumbar or cervical spinal fusion.
    In addition, non-invasive bone growth stimulators are currently 
prescription use only devices under Sec.  801.109 (21 CFR 801.109).

IV. Proposed Reclassification

    In accordance with section 513(f)(3) of the FD&C Act and 21 CFR 
part 860, subpart C, FDA is proposing to reclassify non-invasive bone 
growth stimulator devices under product codes LOF and LPQ from class 
III into class II. This includes devices that generate electrical or 
magnetic fields using CC, PEMF, and CMF, and ultrasonic signals.
    FDA believes that there is sufficient information available by way 
of FDA's accumulated experience with these devices from review of 
premarket submissions, peer-reviewed literature, medical device reports 
(MDRs), and recalls to understand the risks associated with these 
devices to establish special controls that effectively mitigate the 
risks to health identified in section V. In this proposed order, the 
Agency has identified the special controls under section 513(a)(1)(B) 
of the FD&C Act that, together with general controls, would provide a 
reasonable assurance of the safety and effectiveness for non-invasive 
bone growth stimulators to be in class II. Absent the special controls 
identified in this proposed order, general controls applicable to this 
device type are insufficient to provide reasonable assurance of safety 
and effectiveness of the device.
    FDA is proposing to create a classification regulation for non-
invasive bone growth stimulators, which would include devices 
designated under product codes LOF and LPQ. Under this proposed order, 
if finalized, a non-invasive bone growth stimulator will be identified 
as a prescription device. As such, the prescription device must satisfy 
prescription labeling requirements (see Sec.  801.109, Prescription 
devices). Prescription devices are exempt from the requirement for 
adequate directions for use for the layperson under section 502(f)(1) 
of the FD&C Act (21 U.S.C. 352(f)(1)) and 21 CFR 801.5, as long as the 
conditions of Sec.  801.109 are met. In this proposed order, if 
finalized, the Agency has identified the special controls under section 
513(a)(1)(B) of the FD&C Act that, together with general controls, will 
provide a reasonable assurance of the safety and effectiveness for non-
invasive bone growth stimulator devices.
    Section 510(m) of the FD&C Act provides that FDA may exempt a class 
II device from the premarket notification requirements under section 
510(k) of the FD&C Act if FDA determines that premarket notification is 
not necessary

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to provide reasonable assurance of the safety and effectiveness of the 
device. For non-invasive bone growth stimulators, FDA has determined 
that premarket notification is necessary to provide reasonable 
assurance of the safety and effectiveness of the device. Therefore, FDA 
does not propose to exempt these proposed class II devices from 510(k) 
requirements. If this order is finalized, persons who intend to market 
this type of device would need to submit to FDA a 510(k) and receive 
clearance prior to marketing the device.

V. Risks to Health

    Based on available information for non-invasive bone growth 
stimulators, including the 2005 reclassification petition request from 
RS Medical Corp, input from the 2006 Panel, data in PMA applications 
P030034, P850022/S009, and P910066/S011 available to FDA under section 
520(h)(4) of the FD&C Act, published literature, and postmarket 
experience associated with use of these devices, FDA identifies the 
following risks to health associated with non-invasive bone growth 
stimulators:
    a. Failure or delay of osteogenesis--A patient could receive 
ineffective treatment, contributing to failure or delay of osteogenesis 
that may lead to clinical symptoms (e.g., pain) and the need for 
surgical interventions. Ineffective treatment could be a result of 
various circumstances (e.g., inadequate therapeutic signal output or 
device malfunction or misuse).
    b. Burn--A patient or health care professional could be burned from 
the use and operation of the device. This could be a result of various 
circumstances including device malfunction (e.g., electrical fault) or 
misuse of the device (e.g., use while sleeping).
    c. Electrical shock--A patient or health care professional could be 
shocked from the use and operation of the device. This could be a 
result of various circumstances including device malfunction (e.g., 
electrical fault) or misuse of the device (e.g., use of alternating 
current source during treatment).
    d. Electromagnetic interference (EMI)--A patient with electrically 
powered implants (such as cardiac pacemakers, cardiac defibrillators, 
and neurostimulators) could experience an adverse interaction with the 
implanted electrical device via EMI or radiofrequency interference.
    e. Adverse tissue 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.
    f. Adverse interaction with internal/external fixation devices--The 
signal output could be impacted by certain metallic internal or 
external fixation devices leading to inadequate treatment signals, 
device malfunction, or tissue damage.
    g. Adverse biologic effects--A patient may experience adverse 
biologic effects resulting from prolonged exposure to the treatment 
signal via biologic interaction with the treatment signal at a cellular 
level. Excessive energy transmission could cause tissue damage or 
aberrant tissue behavior if signal output parameters exceed established 
safety thresholds.
    The risks to health identified within this proposed order are 
consistent with those identified in the 2005 reclassification petition, 
as amended. The 2006 Panel agreed with these identified risks; however, 
in some cases the risk or accompanying description was reworded for 
clarity in this proposed order (e.g., ``inconsistent treatment or 
ineffective treatment'' is described in terms of risk to health, which 
may entail ``failure or delay in osteogenesis''). Also, the risk of 
adverse biologic effects previously specified risks of carcinogenicity, 
genotoxicity, mutagenicity, and teratological effects. The petitioner 
notes in the amended petition that ``. . . the evidence points to lack 
of genotoxic, carcinogenic, and teratologic potential of the subject 
waveforms,'' which is corroborated by the lack of such reports 
identified in the literature. Although FDA similarly has found a lack 
of such reports, it considers this risk more generally as potential 
deleterious effects at the tissue or cellular level due to signal 
output parameters that exceed established safety thresholds.

VI. Summary of Reasons for Reclassification

    FDA believes that non-invasive bone growth stimulator devices, 
which are intended to promote osteogenesis as an adjunct to primary 
treatments for fracture fixation or spinal fusion, should be 
reclassified from class III to class II and that there is sufficient 
information to establish special controls for the risks identified in 
section V which, in addition to general controls, can provide 
reasonable assurance of safety and effectiveness.
    Specifically, FDA proposes to require clinical performance data as 
a special control to address the risk of failure or delay of 
osteogenesis. FDA review of the literature suggests a high variability 
of treatment efficacy, depending on therapeutic signal and anatomic 
location. This would also address the main concern cited by the 2006 
Panel and FDA with RS Medical's proposal, which led to the 
recommendation to retain non-invasive bone growth stimulators in class 
III, and various comments received in response to the 2007 Notice.
    FDA's proposal would require that clinical performance of any non-
invasive bone growth stimulator device be evaluated in support of the 
intended use. Rather than prescribe specific study requirements, FDA's 
proposal would allow for flexibility in study design and the level of 
clinical evidence needed by taking into consideration certain 
parameters, e.g., the intended use, treatment population, and 
technological characteristics of the device, including any similarities 
between the device and legally marketed predicate device, as 
appropriate.

VII. Summary of Data Upon Which the Reclassification Is Based

    The available evidence demonstrates that there are probable health 
benefits derived from the use of these devices, and that the nature and 
incidence of risks are well known so that special controls can be 
established to adequately mitigate the risks to health. FDA is 
proposing a single device class for non-invasive bone growth 
stimulators, considering that FDA did not identify any unique risks 
associated with the different modalities included in this proposed 
order. FDA has considered and analyzed the following: Data in PMA 
applications P030034, P850022/S009, and P910066/S011 available to FDA 
under section 520(h)(4) of the FD&C Act; information presented at the 
2006 Panel concerning RS Medical's petition to down-classify certain 
non-invasive bone growth stimulators (Ref. 3) and the 2007 Notice; 
peer-reviewed articles that discussed the use of, as well as the 
probable benefits and risks of these devices; reported adverse events 
identified through a search of FDA's Medical Device Reporting (MDR) 
system; and a review of any recalls associated with these devices 
through a search of FDA's Medical Device Recall database.
    In accordance with the ``6-year rule'' described in section 
520(h)(4) of the FD&C Act, FDA considered data contained in three 
original PMAs or supplements, P030034, P850022/S009, and P910066/S011, 
approved for non-invasive bone growth stimulators (Refs. 9 to 11). 
These PMAs/supplements include three different device modalities: A 
PEMF device (P030034), a CC device (P850022/S009), and a CMF device 
(P910066/S011). In review of the reported clinical data in the summary 
of

[[Page 49991]]

safety and effectiveness data documents (SSEDs), the studies conducted 
in support of these devices include a total study size of 831 enrolled 
subjects. The adverse event profile for the devices in each study were 
similar to the control group, with a similar distribution of event 
types. With regards to benefit, the clinical data reported in the SSEDs 
demonstrate an improved rate of bone fusion compared to placebo 
controls, with an 83.6 percent vs. 68.6 percent fusion rate at 6 months 
in P030034 (cervical spine), an 85 percent vs. 75 percent clinical 
success shown in P850022/S009 (lumbar spine), and a 67 percent vs. 43 
percent fusion rate at 9 months in P910066/S011 (lumbar spine).
    Further, FDA performed a literature review to evaluate data related 
to non-invasive bone growth stimulator devices, including studies up to 
the date of the 2006 Panel, as well as any new clinical information 
published since the 2006 Panel.
    Literature published at the time of the 2006 Panel includes a 1953 
seminal paper on the use of electrical signals to stimulate bone 
formation by Yasuda, that reported bone formation in rabbits exposed to 
direct current (DC) stimulation (Ref. 12). In the following decades, 
other researchers expanded on this finding in animal and clinical 
models. In a canine study, a DC stimulation was shown to cause complete 
ossification of the femoral medullary canal (Ref. 13). The first 
clinical case report demonstrated that electrical stimulation could 
treat a non-union fracture (Ref. 14). An early publication regarding 
the effects of DC stimulation on spinal fusion was published by Dwyer 
(Ref. 15). Another early clinical study published by Becker, et al. 
showed successful fracture fusion with a success rate of 77 percent 
(Ref. 16).
    In the 1990s and early 2000s, several literature articles were 
identified assessing the effects of non-invasive bone growth 
stimulators on various anatomic locations. These studies generally 
included various therapeutic modalities (magnitude, frequency, 
duration, etc.) and demonstrated varying results regarding the efficacy 
of these treatments. In two studies of PEMF devices, Basset and Schink-
Ascani (Ref. 17) found a 72 percent fusion rate in patients with 
congenital pseudarthrosis of the tibia, and in a study of non-unions of 
the scaphoid, Adams, et al. (Ref. 18) reported a fusion rate of 69 
percent, as a followup to an earlier study that found a fusion rate of 
80 percent. When looking at the rate of compliance of PEMF devices as a 
factor of effectiveness, Garland, et al. (Ref. 19) found that fusion 
rates ranged from 35.7 percent to 80 percent, depending on how often 
the devices were used. In studies of CC devices, fusion rates in long 
bones varied from 60 percent (Ref. 20), 68.8 percent (Ref. 21), and 
72.7 percent (Ref. 22), to no difference between treatment and a 
placebo-treated group in a study by Fourie and Bowerbank (Ref. 23). 
While there was a large range of observed efficacies, there was no 
reporting of treatment-related adverse events. These reported 
variabilities in efficacy and low adverse event rates were consistent 
with the findings by the 2006 Panel.
    FDA performed a systematic review of published literature to 
identify any new clinical findings since the 2006 Panel. FDA identified 
14 papers that included a combination of retrospective and prospective 
studies. For studies that assessed medical or insurance claims 
databases, radiographs were not always available to determine actual 
fusion. Instead, results were presented in terms of healing rate based 
on patient records or reported outcomes. When radiographs were 
available and analyzed to assess union, results were reported as fusion 
rate.
    Phillips, et al. (Ref. 24) looked at registry data of 2,370 
subjects who were treated with OL1000 (DJO), a CMF device, at various 
fracture sites and reported an average healing rate of 75.1 percent 
(ranging from 57.2 percent in the humerus to 89.7 percent in the finger 
phalanx). DeVries, et al. (Ref. 25) also evaluated the OL1000 device in 
a retrospective analysis of 144 subjects, finding a fusion rate of 57.1 
percent in tibiotalocalcaneal fusions of the ankle.
    With respect to LIPUS, Zura, et al. (Refs. 26 and 27) published two 
papers evaluating subjects in the Exogen (Bioventus) Post Market 
Registry. One of the studies assessed how various patient risk factors 
affected healing rate in 4,190 subjects. The study demonstrated an 
overall healing rate of 95.7 percent, and in another single arm study 
of 767 subjects, showed a healing rate varying from 81.8 percent to 
87.9 percent depending on fracture site. Nolte, et al. (Ref. 28) 
evaluated the Exogen registry in conjunction with a medical claims 
database to examine metatarsal fractures and reported a healing rate of 
97.4 percent overall, while Elvey, et al. (Ref. 29) evaluated 26 cases 
with use of Exogen in hand and wrist non-unions, and found a fusion 
rate of 54 percent to 58 percent. In two smaller studies of the Exogen 
device, Majeed, et al. (Ref. 30) and Mizra, et al. (Ref. 31) both 
evaluated foot and ankle fractures and found 78.7 percent and 67 
percent fusion rate in a 47 and 18 patient study, respectively. Biglari 
(Ref. 32) also performed an observational study using the Exogen device 
and found a much lower fusion rate of 32.8 percent in 60 subjects 
having existing non-unions of various long bones.
    For PEMF devices, a retrospective study by Coric, et al. (Ref. 33) 
on the effects of the CervicalStim (Orthofix) device on 593 subjects 
showed a 73.2 percent fusion rate in the cervical spine at 6 months. In 
a single arm prospective study by Assiotis, et al. (Ref. 34), a 77.3 
percent fusion rate in the tibia was demonstrated with use of the 
Physiostim (Orthofix). Murray and Pethica (Ref. 35) performed a 1,382-
subject retrospective study of use of the EBI device (Zimmer Biomet) 
for non-unions of the scaphoid, tibia, and fibula, and while an 
assessment of healing rates was not performed, the data showed 
reduction in time to healing between 35 percent and 40 percent when the 
device was used as prescribed.
    In addition, two randomized control studies on PEMF devices were 
conducted by Foley, et al. (Ref. 36) and by Streit, et al. (Ref. 37). 
Foley evaluated 323 subjects using the Orthofix CervicalStim device in 
cervical fusion and found an 83.6 percent fusion rate in the treatment 
group compared to a 68.6 percent fusion rate in the control group, with 
no difference in pain scores or adverse events between groups. Streit, 
et al. performed a small, eight subject clinical study using the EBI 
device to treat non-unions of the fifth metatarsal and found the time 
to fusion was reduced on average from 14.7 weeks to 8.9 weeks with the 
use of the device.
    In summary, FDA's literature review resulted in findings that are 
consistent with available clinical data from PMA submissions. These 
studies suggest that there are probable benefits to the use of these 
devices; however, differences in methodology, including differences in 
devices used, treatment waveform and frequency, patient populations, as 
well as anatomic location, could have had significant effects on 
reported device effectiveness, which ranged from 32.8 percent to 97.4 
percent. Regarding safety, the findings from these studies demonstrate 
that the devices are relatively safe as the adverse event profile 
associated with these devices using various modalities was similar to 
controls. Overall, the studies involved 10,566 subjects (including 
control subjects), with only a single report of a serious adverse event 
(Biglari, Ref. 32); however, a direct link to the use of the device 
could not be established for this event.

[[Page 49992]]

    Further, a search of FDA's MDR database was conducted to identify 
all adverse events submitted to FDA up to October 31, 2019, for devices 
approved under product codes LOF and LPQ. The results of the identified 
reports are consistent with the risk profiles identified in both PMA 
applications and literature that were reviewed. FDA's search yielded a 
total of 270 unique MDRs. The most frequently reported events were 
categorized as ``skin reaction/issue'' (n = 187) followed by ``pain'' 
(n = 59) and ``device functional issue'' (n = 21). A review of the 
adverse events regarding skin reactions found that a majority were due 
to irritation from the electrode adhesive or ultrasound gel used. There 
was no apparent difference in risk profile across the various device 
modalities, though the risk of skin irritation was primarily observed 
in the skin-contacting devices (due to the electrodes in the CC device 
and the gel in the LIPUS device). For cases where followup was 
described, patients recovered when treatment was discontinued. In 
addition, 11 reports of ``mass/tumor'' were identified; however, the 
nature of the relationship between the mass/tumor to the device was 
unrelated or unclear. Based upon FDA's assessment of other systematic 
reviews of these devices, no other reports of mass/tumors have been 
identified (Refs. 38 to 42).
    Finally, a search of FDA's Medical Device Recall database was 
conducted. No recalls were found when searching the database for 
devices under product code LOF. Two class 2 recalls were reported for 
devices under product code LPQ; specifically, there was a recall for 
the Exogen Express Bone Healing System and a recall for the Exogen 
4000+ Ultrasound Bone Healing System. Both were posted on August 4, 
2009, and initiated by the manufacturer because of problems with the 
transducer, which may have resulted in a reduced ultrasound output. 
These recalls were terminated on November 18, 2010. These recall events 
reflect the risks to health identified in section V, and FDA believes 
the special controls proposed, in addition to general controls, can 
effectively mitigate the risks identified.

VIII. Proposed Special Controls

    Table 1 outlines the risks to health identified in section V and 
the corresponding mitigation measures proposed to reasonably assure 
safety and effectiveness, which are discussed in more detail below.

 Table 1--Risks to Health and Mitigation Measures for Non-Invasive Bone
                           Growth Stimulators
------------------------------------------------------------------------
       Identified risk to health               Mitigation measures
------------------------------------------------------------------------
Failure or delay of osteogenesis.......  Clinical performance data.
                                         Non-clinical performance
                                          testing.
                                         Software verification,
                                          validation, and hazard
                                          analysis.
                                         Labeling.
Burn...................................  Non-clinical performance
                                          testing.
                                         Electrical safety testing.
                                         Labeling.
Electrical shock.......................  Electrical safety testing.
                                         Labeling.
Electromagnetic interference...........  Electromagnetic compatibility
                                          (EMC) testing.
                                         Labeling.
Adverse tissue reaction................  Biocompatibility evaluation.
                                         Labeling.
Adverse interaction with internal/       Labeling.
 external fixation devices.
Adverse biological effects.............  Non-clinical performance
                                          testing.
                                         Software verification,
                                          validation, and hazard
                                          analysis.
------------------------------------------------------------------------

    The risk of failure or delay of osteogenesis is clinically 
significant. To mitigate this risk, FDA proposes that manufacturers 
provide clinical performance data to demonstrate that the device yields 
positive outcomes (e.g., fusion of the non-union) in accordance with 
its intended use. Further, FDA proposes non-clinical performance 
testing to demonstrate that the device performs as intended under 
anticipated conditions of use to achieve the identified successful 
clinical performance characteristics. This would include verification 
and validation of critical performance characteristics, including 
characterization of the designed outputs of the device as well as the 
outputs that are delivered to the patient, thermal safety and 
reliability testing, reliability testing consistent with the expected 
device use-life, and validation that signal characteristics are within 
safe physiologic limits. Also, FDA proposes appropriate software 
verification, validation, and hazard analysis to ensure that any device 
software performs as intended. Lastly, FDA proposes labeling to provide 
appropriate instructions (e.g., duration, frequency of use) to the end 
user.
    To mitigate the risk of skin burns, FDA proposes non-clinical 
performance testing of the device to verify and validate critical 
performance characteristics, demonstrate thermal safety and 
reliability, validate that signal characteristics are within safe 
physiologic limits, and demonstrate reliability of the device 
consistent with its expected use-life. FDA also proposes electrical 
safety testing to minimize the risk of thermal burns to the patient, 
and specific instructions regarding proper usage and specific warnings 
associated with the risk of burns.
    To mitigate electrical shocks, FDA proposes electrical safety 
testing to minimize the risk of shock to the patient. Furthermore, FDA 
proposes labeling provisions, including instructions on appropriate 
usage and maintenance, and specific warnings regarding electrical 
shock.
    To mitigate electromagnetic interference, FDA proposes 
electromagnetic compatibility testing and labeling to minimize the risk 
of adverse interaction with other electronic devices such as implanted 
electronic devices.
    To mitigate the risk of adverse tissue reactions, FDA proposes a 
biocompatibility evaluation to ensure that the materials used in 
patient-contacting components of the device are safe for skin contact 
and labeling that includes warnings against use on compromised skin or 
when there are known sensitivities, as well as instructions on 
appropriate cleaning of any reusable components.
    To mitigate the risk of adverse interaction with internal/external 
fixation devices, FDA proposes labeling,

[[Page 49993]]

specifically inclusion of appropriate warnings for patients with 
implanted internal/external devices.
    To mitigate the risk of adverse biologic effects, FDA proposes non-
clinical performance testing to verify and validate critical 
performance characteristics of the device, demonstrate thermal safety 
and reliability, validate safety of the signal by reference to known 
biological safety limits, and demonstrate reliability of the device 
over the expected use-life. Furthermore, FDA proposes software 
verification, validation, and hazard analysis.
    If this reclassification is finalized, non-invasive bone growth 
stimulators will be reclassified into class II and would be subject to 
premarket notification (510(k)) requirements under Sec.  807.81. As 
discussed below, the intent is for the reclassification to be codified 
in 21 CFR 890.5870. Firms submitting a 510(k) for non-invasive bone 
growth stimulators will be required to comply with the particular 
mitigation measures set forth in the special controls. Adherence to the 
special controls, in addition to the general controls, is necessary to 
provide a reasonable assurance of the safety and effectiveness of these 
devices.

IX. Analysis of 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. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed order contains no new 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(PRA) (44 U.S.C. 3501-3521) is not required. This proposed order refers 
to previously approved FDA collections of information. These 
collections of information are subject to review by OMB under the PRA. 
The collections of information in part 807, subpart E have been 
approved under OMB control number 0910-0120; the collections of 
information in 21 CFR part 814, subparts A through E, have been 
approved under OMB control number 0910-0231; and the collections of 
information under 21 CFR part 801 have been approved under OMB control 
number 0910-0485.

XI. Codification of Orders

    Under section 513(f)(3) of the FD&C Act, FDA may issue final orders 
to reclassify devices. FDA will continue to codify classifications and 
reclassifications in the Code of Federal Regulations (CFR). Changes 
resulting from final orders will appear in the CFR as newly codified 
orders. Therefore, under section 513(f)(3), in the proposed order, we 
are proposing to codify non-invasive bone growth stimulators in the new 
21 CFR 890.5870, under which non-invasive bone growth stimulators would 
be reclassified from class III to class II.

XII. Proposed Effective Date

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

XIII. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (see ADDRESSES) and are available for 
viewing by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public 
display at https://www.regulations.gov because they have copyright 
restriction. Some may be available at the website address, if listed. 
References without asterisks are available for viewing only at the 
Dockets Management Staff. FDA has verified the website addresses, as of 
the date this document publishes in the Federal Register, but websites 
are subject to change over time.

    1. *Guidance on Section 216 of the Food and Drug Administration 
Modernization Act of 1997, available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-section-216-food-and-drug-administration-modernization-act-1997-guidance-industry-and-fda.
    2. *P790002 Approval available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P790002.
    3. *RS Medical Corporation Reclassification Petition, available 
at https://wayback.archive-it.org/7993/20170405072021/https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4224b1-06-TabB-RSMEDICAL-Petition.pdf.
    4. *FDA's Orthopaedic and Rehabilitation Devices Panel 
transcript and other meeting materials for the June 2, 2006, meeting 
are available at: https://wayback.archive-it.org/7993/20170403222246/https://www.fda.gov/ohrms/dockets/ac/cdrh06.html#orthopaedic.
    5. *Letter from RS Medical requesting withdrawal of petition, 
available at https://www.regulations.gov/document?D=FDA-2005-P-0052-0007.
    6. *FDA letter granting RS Medical's withdrawal request, 
available at https://www.regulations.gov/document?D=FDA-2005-P-0052-0006.
    7. *First Cohort of Results of the 2014-2015 Strategic Priority: 
Strike the Right Balance Between Premarket and Postmarket Data 
Collection (April 2015), available at https://www.fda.gov/media/91437/download.
    8. *Second and Final Cohort of Results of the 2014-2015 
Strategic Priority: Strike the Right Balance Between Premarket and 
Postmarket Data Collection (August 2016), available at https://www.fda.gov/media/99822/download.
    9. *P030034 Summary of Safety and Effectiveness, available at 
https://www.accessdata.fda.gov/cdrh_docs/pdf3/P030034B.pdf.
    10. *P850022/S009 Summary of Safety and Effectiveness, available 
at https://www.accessdata.fda.gov/cdrh_docs/pdf/P850022S009B.pdf.
    11. *P910066/S011 Summary of Safety and Effectiveness, available 
at https://www.accessdata.fda.gov/cdrh_docs/pdf/P910066S011B.pdf.
    12. Yasuda, I., ``The Classic: Fundamental Aspects of Fracture 
Treatment.'' J. Kyoto Med. Soc., 4:395-406, 1953.
    13. Bassett, C.A., R.J. Pawluk, and R.O. Becker, ``Effects of 
Electric Currents on Bone In Vivo.'' Nature, 204: 652-654, 1964.
    14. Friedenberg, Z.B., M.C. Harlow, and C.T. Brighton, ``Healing 
of Nonunion of the Medial Malleolus by Means of Direct Current: A 
Case Report.'' The Journal of Trauma, 11(10):883-885, 1971.
    15. Dwyer, A.F., ``The Use of Electrical Current Stimulation in 
Spinal Fusion.'' The Orthopedic Clinics of North America, 6(1):265-
273, 1975.
    16. Becker, R.O., J.A. Spadaro, and A.A. Marino, ``Clinical 
Experiences With Low Direct Current Stimulation of Bone Growth.'' 
Clinical Orthopaedics and Related Research, 124:75-83, 1977.
    17. Bassett, C.A. and M. Schink-Ascani, ``Long-Term Pulsed 
Electromagnetic Field (PEMF) Results in Congenital Pseudarthrosis.'' 
Calcified Tissue International, 49(3):216-220, 1991.
    18. Adams, B.D., G.K. Frykman, and J. Taleisnik, ``Treatment of 
Scaphoid Nonunion With Casting and Pulsed Electromagnetic Fields: A 
Study Continuation.'' The Journal of Hand Surgery, 17(5):910-914, 
1992.
    19. Garland, D.E., B. Moses, and W. Salyer, ``Long-Term Follow-
up of Fracture Nonunions Treated With PEMFs.'' Contemporary 
Orthopaedics, 22(3):295-302, 1991.
    20. Scott, G. and J.B. King, ``A Prospective, Double-Blind Trial 
of Electrical Capacitive Coupling in the Treatment of Non-Union of 
Long Bones.'' The Journal of Bone and Joint Surgery. American 
volume, 76(6):820-826, 1994.
    21. Abeed, R.I., M. Naseer, and E.W. Abel, ``Capacitively 
Coupled Electrical Stimulation Treatment: Results from Patients With 
Failed Long Bone Fracture Unions.'' Journal of Orthopaedic Trauma, 
12(7):510-513, 1998.
    22. Zamora-Navas, P., A. Borras Verdera, R. Antelo Lorenzo, et 
al., ``Electrical Stimulation of Bone Nonunion With the

[[Page 49994]]

Presence of a Gap.'' Acta Orthopaedica Belgica, 61(3):169-176, 1995.
    23. Fourie, J.A. and P. Bowerbank, ``Stimulation of Bone Healing 
in New Fractures of the Tibial Shaft Using Interferential 
Currents.'' Physiotherapy Research International, 2(4):255-268, 
1997.
    24. Philips, M., J. Baumhauer, S. Sprague, et al., ``Use of 
Combined Magnetic Field Treatment for Fracture Nonunion.'' Journal 
of Long Term Effects of Medical Implants, 26(3):277-284, 2016.
    25. DeVries, J.G., G.C. Berlet, and C.F. Hyer, ``Union Rate of 
Tibiotalocalcaneal Nails With Internal or External Bone 
Stimulation.'' Foot and Ankle International, 33(11):969-978, 2012.
    26. Zura, R., S. Mehta, G.J. Della Rocca, et al., ``A Cohort 
Study of 4,190 Patients Treated With Low-Intensity Pulsed Ultrasound 
(LIPUS): Findings in the Elderly Versus All Patients.'' BioMed 
Central Musculoskeletal Disorders, 16:45, 2015.
    27. Zura, R., G.J. Della Rocca, S. Mehta, et al., ``Treatment of 
Chronic (>1 Year) Fracture Nonunion: Heal Rate in a Cohort of 767 
Patients Treated With Low-Intensity Pulsed Ultrasound (LIPUS).'' 
Injury, 46(10):2036-2041, 2015.
    28. Nolte, P., R. Anderson, E. Strauss, et al., ``Heal Rate of 
Metatarsal Fractures: A Propensity-Matching Study of Patients 
Treated With Low-Intensity Pulsed Ultrasound (LIPUS) vs. Surgical 
and Other Treatments.'' Injury, 47(11):2584-2590, 2016.
    29. Elvey, M.H., R. Miller, K.S. Khor, et al., ``The Use of Low-
Intensity Pulsed Ultrasound in Hand and Wrist Nonunions.'' Journal 
of Plastic Surgery and Hand Surgery, 1-6, 2019 (published online 
ahead of print, November 26, 2019).
    30. Majeed, H., T. Karim, J. Davenport, et al., ``Clinical and 
Patient-Reported Outcomes Following Low Intensity Pulsed Ultrasound 
(LIPUS, Exogen) for Established Post-Traumatic and Post-Surgical 
Nonunion in the Foot and Ankle.'' Foot and Ankle Surgery, S1268-
7731(19)30072-4, 2019 (published online ahead of print, May 19, 
2019).
    31. Mizra, Y.H., K.H. Teoh, D. Golding, et al., ``Is There a 
Role for Low Intensity Pulsed Ultrasound (LIPUS) in Delayed or 
Nonunion Following Arthrodesis in Foot and Ankle Surgery?'' Foot and 
Ankle Surgery, 25(6):842-848, 2019.
    32. Biglari, B., T.M. Yildirim, T. Swing, et al., ``Failed 
Treatment of Long Bone Nonunions With Low Intensity Pulsed 
Ultrasound.'' Archives of Orthopaedic and Trauma Surgery, 
136(8):1121-1134, 2016.
    33. Coric, D., D.E. Bullard, V.V. Patel, et al., ``Pulsed 
Electromagnetic Field Stimulation May Improve Fusion Rates in 
Cervical Arthrodesis in High-Risk Populations.'' Bone and Joint 
Research, 7(2):124-130, 2018.
    34. Assiotis, A., N.P. Sachinis, and B.E. Chalidis, ``Pulsed 
Electromagnetic Fields for the Treatment of Tibial Delayed Unions 
and Nonunions. A Prospective Clinical Study and Review of the 
Literature.'' Journal of Orthopaedic Surgery and Research, 7:24, 
2012.
    35. Murray, H.B. and B.A. Pethica, ``A Follow-up Study of the 
In-Practice Results of Pulsed Electromagnetic Field Therapy in the 
Management of Nonunion Fractures.'' Orthopaedic Research and 
Reviews, 8:67-72, 2016.
    36. Foley, K.T., T.E. Mroz, P.M. Arnold, et al., ``Randomized, 
Prospective, and Controlled Clinical Trial of Pulsed Electromagnetic 
Field Stimulation for Cervical Fusion.'' Spine Journal, 8(3):436-
442, 2008.
    37. Streit, A., B.C. Watson, J.D. Granata, et al., ``Effect on 
Clinical Outcome and Growth Factor Synthesis With Adjunctive Use of 
Pulsed Electromagnetic Fields for Fifth Metatarsal Nonunion 
Fracture: A Double-Blind Randomized Study.'' Foot and Ankle 
International, 37(9):919-923, 2016.
    38. Aleem, I.S., I. Aleem, N. Evaniew, et al., ``Efficacy of 
Electrical Stimulators for Bone Healing: A Meta-Analysis of 
Randomized Sham-Controlled Trials.'' Science Reports, 6:31724, 2016.
    39. Behrens, S.B., M.E. Deren, and K O. Monchik, ``A Review of 
Bone Growth Stimulation for Fracture Treatment.'' Current Orthopedic 
Practice, 24(1):84-91, 2013.
    40. Griffin, X.L., M.L. Costa, N. Parsons, et al., 
``Electromagnetic Field Stimulation for Treating Delayed Union or 
Non-Union of Long Bone Fractures in Adults.'' The Cochrane Database 
of Systematic Reviews, 4:CD008471, 2011.
    41. Griffin, X.L., N. Smith, N. Parsons, et al., ``Ultrasound 
and Shockwave Therapy for Acute Fractures in Adults.'' The Cochrane 
Database of Systematic Reviews, 2:CD008579, 2012.
    42. Hannemann, P.F., E.H.H. Mommers, J.P.M. Schots, et al., 
``The Effects of Low-Intensity Pulsed Ultrasound and Pulsed 
Electromagnetic Fields Bone Growth Stimulation in Acute Fractures: A 
Systematic Review and Meta-Analysis of Randomized Controlled 
Trials.'' Archives of Orthopaedic and Trauma Surgery, 134(8):1093-
1106, 2014.

List of Subjects in 21 CFR Part 890

    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 890 be amended as follows:

PART 890--PHYSICAL MEDICINE DEVICES

0
1. The authority citation for part 890 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.

0
2. Add Sec.  890.5870 to subpart F to read as follows:


Sec.  890.5870  Non-invasive bone growth stimulator.

    (a) Identification. A non-invasive bone growth stimulator provides 
stimulation through electrical, magnetic, or ultrasonic fields. The 
device is for prescription use and is intended to be used externally to 
promote osteogenesis as an adjunct to primary treatments for fracture 
fixation or spinal fusion.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Clinical performance data must support the intended use of the 
device.
    (2) Non-clinical performance testing must demonstrate that the 
device performs as intended under anticipated conditions of use. The 
following must be provided:
    (i) Verification and validation of critical performance 
characteristics of the device, including characterization of the 
designed outputs of the device as well as the outputs that are 
delivered to the patient.
    (ii) Thermal safety and thermal reliability testing.
    (iii) Validation that signal characteristics are within safe 
physiologic limits.
    (iv) Reliability testing consistent with the expected use-life of 
the device.
    (3) Patient-contacting components of the device must be 
demonstrated to be biocompatible.
    (4) Performance data must demonstrate the electrical safety and 
electromagnetic compatibility of the device.
    (5) Appropriate software verification, validation, and hazard 
analysis must be performed.
    (6) Labeling for the device must include the following:
    (i) Warning against use on compromised skin or when there are known 
sensitivities;
    (ii) Appropriate warnings for patients with implanted medical 
devices;
    (iii) A detailed summary of the clinical testing, which includes 
the clinical outcomes associated with the use of the device, and a 
summary of adverse events and complications that occurred with the 
device;
    (iv) A clear description of the device;
    (v) Instructions on appropriate usage, duration, and frequency of 
use;
    (vi) Instructions for maintenance and safe disposal;
    (vii) Instructions for appropriate cleaning of any reusable 
components;
    (viii) Specific warnings regarding user burns, electrical shock, 
and skin irritation; and
    (ix) The risks and benefits associated with use of the device.

    Dated: August 4, 2020.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2020-17543 Filed 8-14-20; 8:45 am]
BILLING CODE 4164-01-P