[Federal Register Volume 84, Number 245 (Friday, December 20, 2019)]
[Rules and Regulations]
[Pages 70003-70013]
[FR Doc No: 2019-27295]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 882

[Docket No. FDA-2014-N-1209]

Neurological Devices; Reclassification of Cranial Electrotherapy
Stimulator Devices Intended To Treat Anxiety and/or Insomnia; Effective
Date of Requirement for Premarket Approval for Cranial Electrotherapy
Stimulator Devices Intended To Treat Depression

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final
order to reclassify the cranial electrotherapy stimulator (CES) device
intended to treat anxiety and/or insomnia, a preamendments class III
device, into class II (special controls) and subject to premarket
notification. FDA is also issuing this final order to require the
filing of a premarket approval application (PMA) or a notice of
completion of a product development protocol (PDP) for CES devices
intended to treat depression (product code JXK) and clarify the device
identification of the CES device to include it as a prescription
device.

DATES: This order is effective on December 20, 2019. See further
discussion in section V, ``Implementation Strategy.''

FOR FURTHER INFORMATION CONTACT: Michael Hoffmann, Center for Devices
and Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Silver
Spring, MD 20993,<PHONE_NUMBER><EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Table of Contents

I. Table of Abbreviations/Commonly Used Acronyms in This Document
II. Background
    A. Reclassification
    B. Requirement for Premarket Approval
    C. Valid Scientific Evidence
III. Public Comments in Response to the Proposed Order
IV. The Final Order
V. Implementation Strategy
    A. Date To File a PMA
    B. Compliance With Special Controls
VI. Codification of Orders
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. References

I. Table of Abbreviations/Commonly Used Acronyms in This Document

------------------------------------------------------------------------
      Abbreviation or acronym                   What it means
------------------------------------------------------------------------
2012 Panel........................  2012 Neurological Devices Panel.
510(k)............................  Premarket Notification.
AC................................  Alternating Current.
CES...............................  Cranial Electrotherapy Stimulator
                                     Device.
CFR...............................  Code of Federal Regulations.
CNS...............................  Central Nervous System.
DC................................  Direct Current.
DSM-5.............................  Diagnostic and Statistical Manual of
                                     Mental Disorders, Fifth Edition.
ECT...............................  Electroconvulsive Therapy Device.
FDA...............................  Food and Drug Administration.
FDASIA............................  Food and Drug Administration Safety
                                     and Innovation Act.
FD&C Act..........................  Federal Food, Drug, and Cosmetic
                                     Act.
FR................................  Federal Register.
IDE...............................  Investigational Device Exemption.
MAUDE.............................  Manufacturer and User Facility
                                     Device Experience.
MDR...............................  Medical Device Reporting.
OMB...............................  Office of Management and Budget.
PDP...............................  Product Development Protocol.
PMA...............................  Premarket Approval Application.
PRA...............................  Paperwork Reduction Act of 1995.
RCT...............................  Randomized Controlled Trial.
Ref...............................  Reference.
RWD...............................  Real-World Data.
RWE...............................  Real-World Evidence.
U.S.C.............................  United States Code.
VSE...............................  Valid Scientific Evidence.
------------------------------------------------------------------------

II. Background

    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 (special controls), and class III
(premarket approval).
    Under section 513(d) of the FD&C Act, devices that were in
commercial distribution before the enactment of the

1976 amendments, May 28, 1976, (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
classification regulation classifying the device; and (3) published a
final classification 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
automatically classified by section 513(f) of the FD&C Act into class
III without any FDA rulemaking process.\1\ 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, in accordance with section
513(i) of the FD&C 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 FD&C Act (21 U.S.C.
360(k)) and part 807 (21 CFR part 807).
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    \1\ CES devices with intended uses outside the scope of those
listed in 21 CFR 882.5800 are considered postamendments devices that
are subject to classification under section 513(f)(1) of the FD&C
Act or, if the relevant requirements are met, under section
513(f)(2) of the FD&C Act.
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    A preamendments device that has been classified into class III and
devices found substantially equivalent by means of premarket
notification (510(k)) procedures to such a preamendments device or to a
device within that type (both the preamendments and substantially
equivalent devices are referred to as preamendments class III devices)
may be marketed without submission of a PMA until FDA issues a final
order under section 515(b) of the FD&C Act (21 U.S.C. 360e(b))
requiring premarket approval.

A. Reclassification

    Under section 515(i)(2) of the FD&C Act, following publication of a
proposed order, a meeting of a device classification panel, and
consideration of the comments of a proposed order, FDA has the
authority to issue an administrative order revising the classification
of a device that FDA has classified as a class III device and for which
no administrative order has been issued calling for PMAs under section
515(b) of the FD&C Act, so that the device is classified into class I
or II. In determining whether to revise the classification of a device
or to require a device to remain in class III, FDA applies the criteria
set forth in section 513(a) of the FD&C Act. Section 513(a)(1)(B) of
the FD&C Act defines class II devices as those devices for which the
general controls in section 513(a)(1)(A) by themselves are insufficient
to provide reasonable assurance of safety and effectiveness, but for
which there is sufficient information to establish special controls
that, together with general controls, provide a reasonable assurance of
safety and effectiveness of a device.
    FDA published a proposed order in the Federal Register of January
22, 2016 (81 FR 3751) and held a meeting of the Neurological Devices
Panel for a discussion of the CES device classification on February 10,
2012 (the 2012 Panel), as described in section 513(b) of the FD&C Act
with respect to CES devices (Ref. 1). FDA also published an order in
the Federal Register of September 10, 2009 (74 FR 16214), that was
issued under section 515(i) of the FD&C Act that required submission of
safety and effectiveness information on CES devices. FDA has considered
the information available to the Agency, including the deliberations of
the 2012 Panel meeting, the reclassification petitions submitted for
these devices, and comments from the public docket to determine that
there is sufficient information to establish special controls to
effectively mitigate the risks to health identified in section III, and
that these special controls, together with general controls, will
provide a reasonable assurance of safety and effectiveness when applied
to CES devices intended to treat anxiety and/or insomnia.
    Therefore, in accordance with sections 513(e)(1) and 515(i) of the
FD&C Act, based on information with respect to the CES device and
taking into account the public health benefit of the use of the CES
device and the nature and known incidence of the risk of the device,
FDA, on its own initiative, is issuing this final order to reclassify
CES devices intended for treatment of anxiety and/or insomnia from
class III to class II (special controls).\2\
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    \2\ FDA notes that the ``ACTION'' caption for this final order
is styled as ``Final amendment; final order,'' rather than ``Final
order.'' Beginning in December 2019, this editorial change was made
to indicate that the document ``amends'' the Code of Federal
Regulations. The 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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B. Requirement for Premarket Approval

    Section 515(b)(1) of the FD&C Act sets forth the process for
issuing a final order requiring PMAs. Specifically, prior to the
issuance of a final order requiring premarket approval for a
preamendments class III device, the following must occur: (1)
Publication of a proposed order in the Federal Register; (2) a meeting
of a device classification panel described in section 513(b) of the
FD&C Act; and (3) consideration of comments from all affected
stakeholders, including patients, payers, and providers. As noted
above, FDA published a proposed order that would require PMAs for CES
devices intended to treat depression in the Federal Register of January
22, 2016. FDA held a meeting of a device classification panel described
in section 513(b) of the FD&C Act with respect to CES devices (Ref. 2).
Finally, FDA received and considered over 300 comments on the proposed
order, as discussed in section III. Therefore, FDA has met the
requirements under section 515(b)(1) of the FD&C Act.
    On July 9, 2012, the Food and Drug Administration Safety and
Innovation Act (FDASIA) (Pub. L. 112-144) was enacted. Section 608(a)
and (b) of FDASIA amended sections 513(e) and 515(b) of the FD&C Act,
amended sections 513(e) and 515(b) of the FD&C Act, changing the
mechanism for, respectively, reclassifying a device and requiring
premarket approval for a preamendments device from rulemaking to an
administrative order. In the Federal Register of December 17, 2018 (83
FR 64443), FDA published a final rule entitled ``Medical Device
Classification Procedures: Incorporating Food and Drug Administration
Safety and Innovation Act Procedures,'' which codified those sections
of FDASIA (Medical Device Classification Procedures Final Rule).
    Although under the FD&C Act a manufacturer of a class III
preamendments device may respond to the call for PMAs by filing a PMA
or a notice of completion of a PDP, in practice, the option of filing a
notice of completion of a PDP has not been used. While corresponding
requirements for PDPs remain available to manufacturers in response to
a final order under section 515(b) of the FD&C Act, for simplicity this
document will refer only to the requirement for the filing and
receiving approval of a PMA.
    Under section 501(f)(2)(B) of the FD&C Act (21 U.S.C.
351(f)(2)(B)), a preamendments class III device may be commercially
distributed without a PMA until 90 days after FDA issues a

final order (or a final rule issued under section 515(b) of the FD&C
Act prior to the enactment of FDASIA) requiring premarket approval for
the device, or 30 months after final classification of the device under
section 513 of the FD&C Act, whichever is later. Because CES devices
that are the subject of this final order were classified in 1979 (44 FR
51770, September 4, 1979), the 30-month period has expired and, thus,
the later of these two time periods is the 90-day period. However, for
currently legally marketed CES devices intended to treat depression,
FDA does not intend to enforce compliance with this 90-day requirement
for an additional 90 days (i.e., 180 days after the effective date of
this final order), as long as a notice of intent to file a PMA is
submitted within 90 days of the effective date of this final order. The
notification of the intent to file a PMA should include a list of all
model numbers for which a manufacturer plans to seek marketing approval
through a PMA. FDA does not intend to enforce compliance with the PMA
requirements with respect to an applicant of a currently legally
marketed CES device intended to treat depression during FDA's review of
the PMA. FDA intends to review any PMA for the device within 180 days
of the date of filing. FDA cautions that under section 515(d)(1)(B)(i)
of the FD&C Act, the Agency may not enter into an agreement to extend
the review period for a PMA beyond 180 days unless the Agency finds
that ``the continued availability of the device is necessary for the
public health.''
    Also, a preamendments device subject to the order process under
section 515(b) of the FD&C Act is not required to have an approved
investigational device exemption (IDE) (see 21 CFR part 812)
contemporaneous with its interstate distribution until the date
identified by FDA in the final order requiring the filing of a PMA for
the device. At that time, an IDE is required only if a PMA has not been
filed and it has been determined that the device is a ``significant
risk'' under Sec.  812.3(m). If the manufacturer, importer, or other
sponsor of the device submits an IDE application and FDA approves it,
the device may be distributed for investigational use. If a PMA is not
filed within 90 days after the issuance of a final order, and the
device is not distributed for investigational use under an IDE, the
device is deemed to be adulterated within the meaning of section
501(f)(1)(A) of the FD&C Act, and subject to seizure and condemnation
under section 304 of the FD&C Act (21 U.S.C. 334) if its distribution
continues. As stated above, FDA does not intend to enforce the
requirement that a PMA be filed or that it has an approved IDE, if
applicable, within 90 days, if a notice of intent to file a PMA is
filed within 90 days of the effective date of this order. Other
enforcement actions include, but are not limited to, the following:
shipment of devices in interstate commerce will be subject to
injunction under section 302 of the FD&C Act (21 U.S.C. 332), and the
individuals responsible for such shipment will be subject to
prosecution under section 303 of the FD&C Act (21 U.S.C. 333). FDA
requests that manufacturers take action to prevent the further use of
devices for which no PMA has been filed.

C. Valid Scientific Evidence

    The evidentiary standard FDA relies on to determine the safety and
effectiveness of a device is valid scientific evidence. Section
860.7(c)(2) (21 CFR 860.7(c)(2)) defines valid scientific evidence. As
described in section III, in finalizing this order, FDA has assessed
the totality of the valid scientific evidence available to FDA. This
evidence includes the literature discussed in the proposed order and
the information provided in response to the proposed order, including
several comments that referenced additional clinical studies. FDA also
considered randomized controlled clinical studies, single arm studies,
and systematic literature reviews that were submitted in the comments.
Single case reports or opinion-based commentary were also submitted to
the dockets for consideration; however, without well controlled
empirical experimentation, these types of information are generally not
considered valid scientific evidence and were not relied upon to
support this reclassification.
    Section 860.7(c)(2) also explains that although random experience
and reports lacking sufficient details to permit scientific evaluation
are not regarded as valid scientific evidence to show safety or
effectiveness, such information may be considered in identifying a
device, the safety and effectiveness of which is questionable (Sec.
860.7(c)(2)). Such random experience and reports lacking sufficient
details to permit scientific evaluation may be early and, sometimes,
informal indications that the device is unsafe and/or ineffective (43
FR 32988 at 32990, July 28, 1978). Where FDA is considering the
classification of a device, such random experience and reports are not
considered valid scientific evidence (Sec.  860.7(c)(2)).
    FDA received many comments from healthcare professionals describing
their practices, the length of time they have been practicing, and the
utilization of CES devices in treating patients with certain
conditions. While FDA acknowledges receiving comments in providing
information for recommending the reclassification of CES devices for
treatment of certain conditions including anxiety, insomnia, and
depression, statements by individual healthcare professionals that they
have used CES devices to treat individual patients do not constitute
valid scientific evidence to demonstrate reasonable assurance of safety
and effectiveness (see Valid Scientific Evidence (VSE) discussion in 48
FR 56778 at 56787-56788, comments 16-21, December 23, 1983 (Ref. 3)).
Such comments do not contain sufficient detail to capture the use of
the device, exposures, and outcomes in the appropriate population and
are not interpretable using informed clinical and scientific judgment.
    FDA also received many comments from patients, or friends and
family of patients, in support of and against reclassification of CES
devices for specific indications for use. These comments described the
experience of the patient that received treatment from a CES device.
FDA acknowledges receiving comments from patients and other individuals
about their positive experiences with CES devices being considered for
reclassification; however, FDA does not consider such comments to be
valid scientific evidence. Because these comments did not contain
sufficient data sources to capture the use of the device, exposures,
and outcomes in the appropriate population and are not interpretable
using informed clinical and scientific judgment, such comments are not
considered valid scientific evidence.
    For medical devices, available evidence traditionally consists of
clinical and non-clinical studies conducted and provided to FDA by the
device manufacturer or sponsor. However, FDA recognizes that a wealth
of data covering medical device experience is routinely collected in
the course of treatment and management of patients. Under certain
circumstances, these real-world data (RWD) may constitute real-world
evidence (RWE), or clinical evidence regarding the usage and potential
benefits or risks of a medical product derived from analysis of RWD,
that may be of sufficient quality to help inform or augment FDA's
understanding of the benefit-risk profile of devices at various points
in their life cycle, and could potentially be valid scientific evidence
used to aid FDA in regulatory decision making. See FDA's

guidance, ``Use of Real-World Evidence to Support Regulatory Decision-
Making for Medical Devices'' (82 FR 41418, August 31, 2017) (Ref. 4),
which clarifies how FDA evaluates RWD to determine whether it may be
sufficiently relevant and reliable to generate the types of RWE that
can be used in FDA regulatory decision making for medical devices,
including potentially generating valid scientific evidence.
    In order to determine the suitability of RWD for regulatory
decision making, FDA will assess the relevance and reliability of the
source and its specific elements. This assessment will be used to
determine whether the RWD source(s) and the proposed analysis can
generate evidence that is sufficiently robust to be used for a given
regulatory purpose. Whether evidence is sufficiently relevant and
reliable for use will, in part, depend on the level of quality
necessary to make a particular regulatory decision (Ref. 4). Although
FDA received numerous comments to the proposed order of patient and
healthcare professionals' experiences with CES devices, many of the
comments did not include sufficient data sources as evidence for
consideration of reclassification of CES devices intended for treatment
of depression in finalizing this order.

III. Public Comments in Response to the Proposed Order

    On January 22, 2016, FDA published in the Federal Register a
proposed order to reclassify from class III to class II, subject to
premarket notification, the CES devices intended to treat anxiety and/
or insomnia and to require filing of a PMA for CES devices intended to
treat depression. The comment period on the proposed order closed on
April 21, 2016.
    In response to the January 22, 2016, proposed order, FDA received
over 300 comments from industry, professional societies, trade
organizations, and individual consumers by the close of the comment
period, each containing one or more comments on one or more issues.
    We describe and respond to the comments in this section of the
document. The comments are grouped based on common themes; we grouped
similar comments together under the same number and listed them
numerically. The number assigned to each group is purely for
organizational purposes and does not signify the comment's value or
importance or the order in which comments were received. Please note
that in some cases we separated different issues discussed by the same
commenter and designated them as distinct comments for purposes of our
responses.
    (Comment 1) FDA received numerous comments in favor of the proposed
reclassification of CES for treatment of anxiety and/or insomnia into
class II with special controls.
    (Response 1) Based on the consideration of the deliberation at the
2012 Panel meeting, valid scientific evidence, and review of relevant
scientific articles and comments received in response to the 2016
proposed order, FDA continues to believe that CES devices intended to
treat anxiety and/or insomnia should be reclassified from class III to
class II (Refs. 1, 5, and 6), as initially specified in the proposed
order. FDA has made this determination based upon an assessment (or, in
some cases, reassessment) of the following sources of information: (1)
Published literature referenced in the Executive Summary to the 2012
Panel; (2) comments and literature received in public dockets including
the call for safety and effectiveness information for all preamendments
class III devices (74 FR 16214), the 2012 Panel (76 FR 6625, February
7, 2011), and the proposed order (81 FR 3751); and (3) review of
medical device reports (MDRs) in the FDA Manufacturer and User Facility
Device Experience (MAUDE) database. The reevaluation of the scientific
evidence presented to and discussed at the 2012 Panel meeting, and the
review of additional post-2012 scientific information, further supports
this finding. Based on the totality of this available evidence, FDA has
determined that the designated special controls, together with general
controls, mitigate the risks to health associated with use of CES for
the specific indications of treating anxiety and/or insomnia and
provide a reasonable assurance of safety and effectiveness, as
initially specified in the proposed order. Table 1 identifies the risks
associated with CES for treatment of anxiety and/or insomnia and the
necessary mitigation measures by the required special controls. In this
final order, FDA has included a non-substantive, clarifying edit in
table 1 for the mitigation measures for skin irritation by changing
``biocompatibility testing'' to ``biocompatibility evaluation'' in
table 1. As a result, FDA is adopting the special controls identified
in the proposed order for CES devices for the treatment of anxiety and/
or insomnia. Therefore, FDA has determined that the proposed special
controls identified in this final order, in combination with general
controls, provide a reasonable assurance of safety and effectiveness of
CES for treatment of anxiety and/or insomnia.
    FDA will also create a new product code for CES devices intended
for the treatment of anxiety and/or insomnia.

     Table 1--Identified Risks to Health and Mitigation Measures for
           Treatment of Anxiety and/or Insomnia in CES Devices
------------------------------------------------------------------------
            Identified risk                    Mitigation measures
------------------------------------------------------------------------
Ineffective treatment..................  Clinical Performance Testing.
                                         Non-clinical (bench)
                                          performance testing.
                                         Characterization and
                                          Verification of technical
                                          Parameters.
                                         Labeling.
Skin irritation........................  Biocompatibility Evaluation
                                          Labeling.
Headaches..............................  Clinical Performance Testing
                                          Labeling.
Dizziness..............................  Clinical Performance Testing
                                          Labeling.
Electrical shocks and burns............  Electrical safety and
                                          electromagnetic compatibility
                                          testing.
                                         Software verification,
                                          validation and hazard
                                          analysis.
------------------------------------------------------------------------

    (Comment 2) Several comments opposed maintaining the classification
of CES for the treatment of depression in class III and the call for
PMAs for the following reasons: (1) There are little to no safety or
effectiveness concerns; (2) maintaining the classification of CES for
treatment of depression as class III is inconsistent with the statutory
definition of class III because, among other things, it does not
``present a potential unreasonable risk of illness or

injury'' based on valid scientific evidence available at the time of
premarket clearance; (3) CES for treatment of depression may be
addressed by requiring clinical performance data to support a premarket
notification (510(k)); and (4) there is prevalence of comorbidity of
anxiety disorders and depression that supports the reclassification of
CES for treatment of depression to class II.
    (Response 2) Based on the totality of evidence, including
consideration of the deliberation at the 2012 Panel meeting, recent
review of relevant scientific articles, and comments received in
response to the 2016 proposed order (81 FR 3751), FDA continues to
disagree with reclassification of CES for treatment of depression into
class II. FDA has identified the following reasons for maintaining CES
for the treatment of depression in class III and the call for PMAs:
    (Response 2A) FDA disagrees that there are no safety or
effectiveness concerns with reclassifying CES devices for treatment of
depression into class II. As noted previously, the evidentiary standard
FDA relies on to determine the safety and effectiveness of a device is
valid scientific evidence as defined in Sec.  860.7(c)(2). In
finalizing this order, FDA has assessed the totality of the valid
scientific evidence for treatment of depression that was discussed at
the 2012 Panel meeting and provided in comments to the 2016 proposed
order, including several comments that referenced additional clinical
studies. In addition, this assessment also included an updated analysis
of the publicly available safety data in FDA's MAUDE database and an
updated review of the literature.
    For the treatment of depression, FDA concluded in the 2016 proposed
order that there was insufficient information to establish special
controls that, in addition to general controls, would provide
reasonable assurance of safety and effectiveness of CES devices for
treating depression (81 FR 3751 at 3760).
    The Agency's previous literature assessment identified 12 papers
that examined the effect of CES on measures of depression (6 Randomized
Controlled Trials (RCT) and 6 observational studies). In most RCTs,
depression levels did not differ significantly between patients who
were treated with active CES compared to those treated with placebo
(Refs. 7-11), although one randomized trial by Hearst et al. reported
fewer depression symptoms in the active CES treatment versus placebo
groups (Ref. 12). Of the six observational studies that were reviewed,
four studies reported improvement in depression symptoms after
treatment with CES (Refs. 13-16). Moore et al. also reported
improvement in depression post- (versus pre-) CES treatment, but the
findings were not statistically significant (Ref. 17). The
observational study by Marshall et al. reported no difference in
depressive symptoms between the CES and placebo arms (Ref. 18).
Moreover, the observational study Marshall et al. reported no
difference in depressive symptoms between the CES and placebo arms
(Ref. 18).
    Among the intended uses of insomnia, anxiety, and depression, the
evidence supporting the effectiveness of CES for treating depression
was the weakest. As established in section 513(a)(1)(C) of the FD&C Act
and Sec.  860.3(c)(3), a device is in class III if insufficient
information exists to determine that general controls and/or special
controls are sufficient to provide reasonable assurance of its safety
and effectiveness and the device is purported or represented to be for
a use that is life-supporting or life-sustaining, or for a use which is
of substantial importance in preventing impairment of human health, or
if the device presents a potential unreasonable risk of illness or
injury. FDA believes that the risks to health, identified earlier in
this section, for the use of CES devices for treating depression, in
the absence of an established positive benefit-risk profile, presents a
potential unreasonable risk of illness or injury. FDA therefore
concluded that there was insufficient information regarding the risks
and benefits of the device for FDA to establish special controls that,
in combination with general controls, would provide reasonable
assurance of the safety and effectiveness of CES for treating
depression.
    As of the date of this final order, there is still insufficient
information to establish special controls that, in addition to general
controls, will provide reasonable assurance of safety and effectiveness
of CES devices for treating depression. FDA has reviewed all the
scientific literature that was cited in comments submitted to the
docket of the 2016 proposed order. While these articles had not been
discussed specifically in the proposed order, FDA is clarifying that
they are not-supportive to the reclassification of CES for treatment of
depression. Specifically, these articles have significant shortcomings,
such as lacking a well-controlled design (Ref. 19), lacking a diagnosis
for eligibility (Ref. 20), having uncertain correlation with diagnostic
criteria used in the United States (Ref. 21), containing an exclusion
for unipolar depression (Ref. 22), lacking an appropriately matched
control group (Ref. 23), and/or including studies that did not focus
specifically on CES (Refs. 24 and 25). In one case, while FDA
considered a reference supportive of reclassification for anxiety,
there was insufficient information to support reclassification for
depression because the two groups were not matched with respect to the
diagnosis (Ref. 26). Thus, these articles do not justify FDA changing
the classification of CES devices intended for treatment of depression.
Following the closure of the comment period for the 2016 proposed
order, as part of the assessment of the current state of scientific
evidence for CES devices, FDA also conducted an updated review of
scientific literature. The search used a similar methodology as
previous searches conducted in support of the preceding Federal
Register orders, and the 2012 Panel meeting. As part of FDA's
systematic identification of literature, FDA did not identify studies
regarding the use of CES to treat depression as the primary diagnosis.
However, FDA did identify four studies either where symptoms of
depression were studied in populations of subjects where the primary
diagnosis was not a psychiatric condition (Refs. 27 to 29), or where
there was one single session administered to examine acute
physiological changes only (Ref. 30). FDA evaluated these studies to
determine whether they were designed to assess the use of CES to treat
depressive disorders that are recognized by the clinical community as
identified in the Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition (DSM-5, published 2013) (Ref. 31). FDA
concluded that the four studies published after January 1, 2016,
through November 1, 2019, did not contribute sufficient information in
the form of valid scientific evidence to demonstrate that the subjects
met the criteria for any recognized depressive disorder, as defined in
DSM-5 (Ref. 31).
    In addition, FDA conducted a review of adverse event reporting for
CES devices since the publication of the proposed order. The FDA's
MAUDE database search resulted in a total of three additional CES-
related medical device reporting (MDRs) and one possibly pertinent to
CES between January 1, 2016, and September 1, 2019. Two MDRs were
injury reports submitted by voluntary reporters for a CES device
manufacturer. A third MDR was a malfunction report submitted by a
device manufacturer for an implanted intestinal stimulator and noted
concomitant use of an unspecified CES

device and a fourth MDR report was used to ``improve brain
functioning'' with a report of a third-degree burn. Although there are
a low number of MDRs related to CES devices, the adverse reports for
treatment of depression are only one factor (e.g., other factors may
include the patient population targeted, alternative therapies) for FDA
to consider in concluding that there is insufficient information to
establish special controls that, in combination with general controls,
will provide a reasonable assurance of safety and effectiveness of CES
for the treatment of depression. FDA continues to believe that the
risks to health identified for the use of CES devices for treating
depression, in the absence of an established positive benefit-risk
profile, presents a potential unreasonable risk of illness or injury.
Thus, following the review of all the evidence presented, FDA has
concluded that there is insufficient evidence to establish special
controls that, in addition to general controls, will provide a
reasonable assurance of safety and effectiveness for CES in treating
depression. Accordingly, it is appropriate to maintain CES for
treatment of depression in class III.
    (Response 2B) FDA disagrees that maintaining the classification of
CES for treatment of depression in class III is inconsistent with the
statutory definition of class III. Section 513(a)(1)(C) of the FD&C Act
(21 U.S.C. 360c(a)(l)(C)) defines class III, premarket approval as the
following:

    (1) A device which because it cannot be classified as a class I
device because insufficient information exists to determine that the
application of general controls are sufficient to provide reasonable
assurance of the safety and effectiveness of the device, (2) cannot
be classified as a class II device because insufficient information
exists to determine that the special controls described in
subparagraph (B) would provide a reasonable assurance of its safety
and effectiveness, and is purported or represented to be for a use
in supporting or sustaining human life or for a use which is of
substantial importance in preventing impairment of human health, or
(3) presents a potential unreasonable risk of illness or injury.

    Both class II and class III devices may present a potential
unreasonable risk of illness or injury; however, the distinction is
that devices in class II have sufficient evidence from which special
controls can be established, in combination with general controls, that
will provide a reasonable assurance of safety and effectiveness. As
stated above, the CES proposed order indicated that there was
insufficient evidence that would allow FDA to develop special controls
that, in combination with general controls, would provide a reasonable
assurance of safety and effectiveness of CES devices intended for
treatment of depression, and FDA has determined that there is not
sufficient new information that would satisfy that requirement to
mitigate a potential unreasonable risk of illness or injury.
    (Response 2C) Some comments stated that CES for treatment of
depression can be addressed by requiring clinical performance data to
support a premarket notification (510(k)). However, in order to
classify CES into class II for the treatment of depression, it is
necessary for the evidence to first exist that permits the
establishment of special controls to provide a reasonable assurance of
safety and effectiveness. As mentioned above, FDA has conducted an
extensive review of scientific literature and such evidence was not
available at the time of the proposed order, and there continues to be
a lack of effectiveness data to mitigate a potential unreasonable risk
of illness or injury for CES devices for treatment of depression.
Furthermore, there is lack of sufficient evidence to support
development of special controls that would provide a reasonable
assurance of safety and effectiveness for CES devices in treating
depression.
    (Response 2D) A comment also stated that there is a prevalence of
comorbidity of anxiety disorders and depression that supports the
reclassification of CES for treatment of depression to class II. While
the articles by Jansson-Frojmark et al. and Coplan et al. (Refs. 24 and
25) discuss this connection, they are not studies of CES (as mentioned
above) (Refs. 24 and 25). The available evidence where CES was
investigated in an anxiety population where depression was a
comorbidity is Barclay et al. (Ref. 6). This study, which investigated
the use of CES to treat primary anxiety, also included subjects with
``comorbid depression'' provided that a subject's anxiety was more
severe than the depression (Ref. 6). However, the study does not
clearly demonstrate that these subjects met the DSM 5 criteria for a
recognized depressive disorder (Ref. 31). Therefore, the evidence is
insufficient to enable FDA to establish a reasonable assurance of
safety and effectiveness to support reclassifying CES devices intended
for treatment of depression from class III to II.
    (Comment 3) A few comments supported the proposal for a call for
PMAs for treatment of depression because they believed there was a lack
of valid scientific evidence to support the effectiveness of CES
devices for treatment of depression.
    (Response 3) FDA agrees with the comments to maintain the
classification of CES for treatment of depression as class III. As
stated in the preceding response, FDA has determined that there is a
lack of sufficient evidence that would satisfy the requirement to
mitigate ``a potential unreasonable risk of illness or injury'' to
warrant the reclassification for depression into class II with special
controls. As a result, there is insufficient evidence to establish
special controls to provide a reasonable assurance of safety and
effectiveness of CES devices for treatment of depression.
    (Comment 4) One comment compared the reclassification of CES with
that of Electroconvulsive Therapy (ECT) devices. Specifically, the
commenter states that FDA's reclassification of ECT devices, which
provide the largest amount of electricity, to class II should equate to
reclassification of CES devices, which provide less electricity, as
class I.
    (Response 4) FDA disagrees with this commenter's comparison of ECT
and CES devices. The safety and effectiveness evidence in support of
reclassifying ECT for specific uses was substantial and demonstrated
benefits more consistently, in comparison to the evidence evaluated for
reclassifying CES intended for treatment of depression from class III
to II, although sufficient information exists to establish special
controls that, in addition to general controls, will provide reasonable
assurance of safety and effectiveness of the CES devices intended for
treatment of anxiety and/or insomnia, as discussed above. FDA assessed
the totality of the valid scientific evidence that was provided in
response to the proposed ECT order, including several comments that
referenced new clinical studies. Several of these studies included
safety and effectiveness data for adult as well as adolescent patients
as well as randomized controlled clinical studies, open-label
observational trials, case series reports, systematic literature
reviews, and practice guidelines that were submitted in the comments.
Additionally, the final order for the reclassification of ECT devices
published in the Federal Register (December 26, 2018, 83 FR 66103)
identifies ECT devices as applying a brief electrical stimulation of
the brain to produce a seizure, while CES devices provide lower
stimulation current that is not intended to result in seizure in
patients. FDA also believes that general controls alone are
insufficient to mitigate the risks to

health of CES devices; therefore, the special controls are also needed
to provide reasonable assurance of safety and effectiveness for CES
devices intended for treating anxiety and/or insomnia.
    (Comment 5) Several comments oppose the proposal to identify CES
devices as prescription devices. Also, one comment opposes a
prescription for treatment of depression and suggests that Federal and
State laws mandate that physicians advise patients about CES before
prescribing psychiatric, sleeping and/or pain medications so that
patients can make a reasonable decision and possibly reduce medication-
induced mental health issues.
    (Response 5) As stated in the proposed order, the CES device is a
prescription only device for all three intended uses, i.e., anxiety,
insomnia, and depression, and may not be safe for use except under the
authorization of a healthcare professional licensed by law to
administer the use of the device. As such, the device identification in
Sec.  882.5800(a) (21 CFR 882.5800(a)) has been revised to clarify that
CES is a prescription device in accordance with 21 CFR 801.109. Per
Sec.  801.109(c), a prescription device must include labeling that
describes the indications and other information for use, such as
methods, frequency and duration of administration, any relevant
hazards, contraindications, side effects, and precautions under which
the healthcare professionals can use the device safely (see Sec.
882.5800(b)). Accordingly, healthcare professionals will have access to
and be aware of the warnings and precautions in the labeling, and as
such, healthcare professionals should be adequately informed of the
risks associated with these devices. The healthcare professional can
inform the patients of the relevant risks. The warning and precaution
statements are an appropriate mitigation for CES intended for the
treatment of anxiety and insomnia.
    (Comment 6) Several comments expressed the desire for insurance
coverage to reduce the cost of the device.
    (Response 6) FDA understands the concerns with cost and insurance
coverage. However, FDA has no authority over commercial health
insurance carriers. Under sections 513(e) and 515(i) of the FD&C Act,
FDA has no authority to consider as part of a classification decision
whether an indication or a device is covered by commercial health
insurance companies. FDA recommends that patients check with their
insurance company regarding coverage before receiving CES treatment.
    (Comment 7) One comment stated that a manufacturer's website of a
currently marketed CES device includes misleading marketing material
that may persuade consumers to use this device. The comment also claims
that the marketed CES device is not effective.
    (Response 7) FDA takes seriously any alleged claims of false or
misleading claims by a device manufacturer. Several complaints have
been received by the agency claiming that CES devices have not
demonstrated effectiveness for treating anxiety and/or insomnia. FDA
reviews all complaints and follows the appropriate steps to address
complaints received. As a result, FDA continues to believe that the
special controls proposed and finalized in this final order should
include clinical performance data that demonstrates, among other
things, that a CES device, when used as directed, will provide
clinically meaningful results in the indicated patient population and
provide a reasonable assurance of effectiveness for the intended use of
CES devices for treating anxiety and/or insomnia. FDA also believes
that a call for PMAs is appropriate for CES devices for treatment of
depression to mitigate the potential unreasonable risk of illness or
injury.
    (Comment 8) One comment suggested FDA should not rely on the
recommendations of the 2012 Panel because the meeting was not conducted
properly due to the following alleged errors by FDA: (1) Failure to
include any panel members with the knowledge of or experience with CES
devices; (2) failure to allow all interested parties ample time to
present at the 2012 Panel; and (3) failure to provide adequate
information by not presenting to the 2012 Panel for consideration the
comments received from the proposed rule published in the Federal
Register on August 8, 2011 (76 FR 48062), or articles of valid
scientific evidence.
    (Response 8) FDA believes the 2012 Panel was properly conducted
based on the requirements under the FD&C Act. FDA also disagrees with
the alleged errors stated for the following reasons.
    First, FDA has specific procedures and protocols for all panel
meetings that are followed to provide an objective outcome of the panel
meetings. For more information, please refer to the FDA's Guidance,
``Procedures for Meetings of the Medical Devices Advisory Committee''
(Ref. 32). Also, FDA may exclude a healthcare professional from
participating on an advisory committee if the person has a conflict of
interest. Although a healthcare professional was excluded from the 2012
Panel, there was adequate representation of professionals with
experience in using CES devices on the 2012 Panel. For more information
on conflicts of interest as it relates to FDA advisory committees,
please refer to the relevant FDA guidance entitled, ``Public
Availability of Advisory Committee Members' Financial Interest
Information and Waivers'' (Ref. 33).
    Second, under section 513(b)(6)(A)(iii) of the FD&C Act, any person
whose device is specifically the subject of review by a panel shall
have the same opportunity as the Secretary to participate in meetings
of the panel, including, subject to the discretion of the panel
chairperson, by designating a representative who will be provided a
time during the panel meeting to address the panel for the purpose of
correcting misstatements of fact or providing clarifying information,
and permitting the person or representative to call on experts within
the person's organization to address such specific issues in the time
provided. Furthermore, section 513(b)(6)(B) of the FD&C Act, before and
after the enactment of the 21st Century Cures Act (Pub. L. 114-255),
requires that meetings shall provide adequate time for initial
presentations; and encourage free and open participation by all
interested persons. FDA provided the appropriate allocated time for all
interested parties to speak or present at the 2012 Panel and for the
2012 Panel to consider their concerns with CES devices (Ref. 32).
    Third, during the 2012 Panel, FDA's presentation included a listing
of scientific articles (Refs. 1 and 2) and the 2011 proposed rule (76
FR 48062) with a summary of the comments received to the docket for the
proposed rule. Therefore, the 2012 Panel members received sufficient
information on the 2011 proposed rule and other information to make an
informed decision on the classification of CES devices.
    (Comment 9) Some comments questioned FDA's effectiveness claims for
reclassification and suggested that more research is needed on CES
before the device should be reclassified. One comment stated that the
proposed order did not provide sufficient valid scientific evidence
through tests to prove the effectiveness of CES for reclassification
into class II because most of the studies conducted were inconclusive.
    (Response 9) FDA disagrees with these comments. The proposed order
acknowledged that no individual published study on CES provides

definitive evidence of effectiveness of CES for the treatment of
anxiety and/or insomnia. FDA noted, however, that in 18 of the 24 small
published studies (those that enrolled fewer than 50 patients) that
included assessments of anxiety and/or insomnia, each study had a main
finding that indicated a greater benefit of CES versus control for at
least 1 of the outcome measures evaluated. Furthermore, CES treatment
group outcomes improved in all large published studies (although not
all studies demonstrated improvement compared with control patients),
including two studies identified after the 2012 Panel (Refs. 5 and 6).
Based on the available information, the proposed order concluded that
there is valid scientific evidence of effectiveness for CES in the
treatment of anxiety and/or insomnia. Since the proposed order was
published, FDA has not become aware of new information that changes
this position.
    Importantly, however, FDA acknowledges that because different CES
devices were evaluated and the methodology of CES delivery (e.g.,
electrode placement, stimulation parameters, duration and frequency of
treatment sessions) varied, the data are insufficient to determine the
technical performance parameters, adequate directions for use, and
warnings for unsafe use for specific devices, and whether the devices,
when used in accordance with such directions, will provide clinically
meaningful results. As explained in the proposed order, although the
evidence available to FDA collectively demonstrates a class effect of
CES devices for treating anxiety and/or insomnia, it cannot be
concluded, based on available information alone, that specific CES
devices will be effective for treating anxiety and/or insomnia. As a
result, FDA believes that the special controls must include clinical
performance data that demonstrates that a device, when used as directed
(including instructions for electrode placement, stimulation
parameters, duration and frequency of treatment sessions, and other
relevant characteristics), will provide clinically meaningful results
in the indicated patient population and provide a reasonable assurance
of safety and effectiveness for the intended use of CES devices for
treating anxiety and/or insomnia.
    (Comment 10) One comment recommended that FDA should obtain valid
scientific evidence which supports that Central Nervous System (CNS)
disorders are treatable with the use of CES.
    (Response 10) The category of ``CNS disorders'' is very broad,
while the classification of CES devices is only based on the treatment
of anxiety, insomnia and/or depression, as they are the only
indications that have been currently allowed for marketing
authorization; therefore, valid scientific evidence for all CNS
disorders are not relevant for this reclassification. This final order
does not address the treatment of broader CNS disorders as they are
outside the scope of this final order. Manufacturers seeking to
indicate a device for a specific CNS disorder would be responsible for
the collection of any valid scientific evidence that may be necessary
to support a new indication for marketing CES devices.
    (Comment 11) One comment suggests that FDA should correctly
categorize CES as either Direct Current (DC) or Alternating Current
(AC) stimulation and not whether it is the same waveform as the
predicate CES devices used. Comment also suggests that clinical trials
are necessary to determine regions of influence by current.
    (Response 11) Based on our interpretation of this comment, FDA
believes that CES devices could use AC or DC stimulation and that
clinical trials conducted to comply with the special controls could be
used to characterize the degree of activation in different brain
regions.

IV. The Final Order

    Based on the information discussed in the preamble to the proposed
order (81 FR 3751), the comments received for the proposed order, a
review of medical device reports in the FDA MAUDE database, a review of
current scientific literature, and 2012 Panel deliberations (Ref. 1),
FDA concludes that special controls, in conjunction with general
controls, will provide reasonable assurance of the safety and
effectiveness of CES devices intended for treatment of anxiety and/or
insomnia. Under sections 513(e), 515(b), and 515(i) of the FD&C Act,
FDA is adopting its findings, as published in the preamble to the
proposed order. For the reasons described in section III, FDA is
issuing this final order to reclassify CES devices intended for
treatment of anxiety and/or insomnia from class III to class II
(special controls). CES devices intended to treat anxiety and/or
insomnia must comply with the special controls following the effective
date of the final order. However, FDA does not intend to enforce
compliance with the special controls for currently legally marketed CES
devices intended to treat anxiety and/or insomnia until 1 year after
the effective date of the final order.
    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 to provide reasonable assurance of the safety and
effectiveness of the device. For the CES devices classified as class II
(i.e., for treatment of anxiety and/or insomnia), FDA has determined
that premarket notification is necessary to provide reasonable
assurance of the safety and effectiveness of the device. Therefore,
this device type is not exempt from premarket notification
requirements. Persons who intend to market this type of device must
submit to FDA a premarket notification, prior to marketing the device,
which contains information about the device they intend to market.
    FDA is also requiring the filing of a PMA for CES devices intended
for the treatment of depression under section 515(b) of the FD&C Act.
Under section 515(b)(1)(A) of the FD&C Act, PMAs for CES devices are
required to be filed on or before 90 days after the effective date of a
final order.

V. Implementation Strategy

A. Date To File a PMA

    In accordance with section 515(b) of the FD&C Act, CES devices
intended to treat depression must have a PMA or a notice of completion
of PDP filed with the Agency by March 19, 2020. An applicant whose
device was legally in commercial distribution before May 28, 1976, or
whose device has been found to be substantially equivalent to such a
device, will be permitted to continue marketing such class III devices
during FDA's review of the PMA provided that the PMA is timely filed.
For currently legally marketed CES devices intended to treat
depression, FDA does not intend to enforce compliance with this 90-day
requirement for an additional 90 days (i.e., 180 days after the
effective date of any final order), as long as notice of intent to file
a PMA is submitted within 90 days of the effective date of the final
order. The notification of the intent to file a PMA submission should
include a list of all model numbers for which a manufacturer plans to
seek marketing approval through a PMA. FDA does not intend to enforce
compliance with the PMA requirements with respect to an applicant of a
currently legally marketed CES device intended to treat depression
during FDA's review of the PMA. FDA intends to review any PMA for the
device within 180 days of the date of filing. FDA cautions that under
section 515(d)(1)(B)(i) of the FD&C Act, the

Agency may not enter into an agreement to extend the review period for
a PMA beyond 180 days unless the Agency finds that ``the continued
availability of the device is necessary for the public health.'' If a
PMA for a class III device is not filed with FDA by March 19, 2020, the
device will be deemed adulterated under section 501(f) of the FD&C Act.
Table 2 shows the regulatory timetable for currently legally marketed
CES devices intended to treat depression.

     Table 2--Timetable for CES Devices Intended To Treat Depression
------------------------------------------------------------------------
                               Timetable for which
                               FDA does not intend   Distribution period
                                   to enforce            (time after
                                compliance (time      effective date of
                              after effective date      final order)
                                 of final order)
------------------------------------------------------------------------
Intent to file a PMA........  90 days.............  Devices included in
                                                     an intent to file:
                                                     180 days.
File a PMA..................  Devices included in   Until a not
                               an intent to file:    approvable decision
                               180 days.             or denial decision
                              Devices not included   is issued; can
                               in an intent to       continue
                               file: 90 days.        distribution if an
                                                     approval order is
                                                     issued.
------------------------------------------------------------------------

    Under Sec.  812.2(d), the exemption from the requirements of the
IDE regulations for preamendments class III devices in Sec.
812.2(c)(1) and (2) will cease to apply to CES devices indicated for
depression that are: (1) Not legally on the market on or before March
19, 2020 or (2) legally on the market on or before March 19, 2020 but
for which a PMA or notice of completion of a PDP is not filed by March
19, 2020, or for which PMA approval has been denied or withdrawn.
    The device may be distributed for investigational use only if the
requirements of the IDE regulations are met. The requirements for
significant risk devices include submitting an IDE application to FDA
for its review and approval. An approved IDE is required to be in
effect before an investigation of the device may be initiated or
continued under Sec.  812.30. FDA, therefore, cautions that IDE
applications should be submitted to FDA at least 30 days before March
19, 2020 to avoid interrupting investigations. There will be no
extended period for filing an IDE nor exemption from IDE requirements,
and studies may not be initiated without appropriate IDE approvals,
where necessary.

B. Compliance With Special Controls

    Following the effective date of this final order, CES devices
intended to treat anxiety and/or insomnia must comply with the special
controls. FDA notes that a firm whose CES device was legally in
commercial distribution before May 28, 1976, or whose device was found
to be substantially equivalent to such a device and who does not intend
to market such device for uses other than to treat insomnia and/or
anxiety, may remove such intended uses from the device's labeling.
    The special controls identified in this final order are effective
as of the date of publication of this order, December 20, 2019. CES
devices intended to treat anxiety and/or insomnia must comply with the
special controls following the effective date of this order. However,
FDA does not intend to enforce compliance with the special controls for
currently legally marketed CES devices intended to treat anxiety and/or
insomnia until 1 year after the effective date of the final order.
Manufacturers who wish to continue to legally market a CES device for
treatment of anxiety and/or insomnia must submit an amendment to their
previously cleared 510(k) that demonstrates compliance with the special
controls by December 21, 2020. Such amendment will be added to the
510(k) file but will not serve as a basis for a new substantial
equivalence review. A submitted 510(k) amendment in this context will
be used solely to demonstrate to FDA that a CES device is in compliance
with the special controls. If a 510(k) amendment is not submitted by
December 21, 2020 or if FDA determines that the amendment does not
demonstrate compliance with the special controls, then this compliance
policy would not apply, and FDA would intend to enforce compliance with
these requirements. In that case, the device is deemed adulterated
under section 501(f)(1)(B) of the FD&C Act as of the date of FDA's
determination of noncompliance or 1 year after the effective date of
the final order, whichever is sooner.
    For models of CES devices intended to treat anxiety and/or insomnia
that have not been legally marketed prior to December 20, 2019, or
models that have been legally marketed but are required to submit a new
510(k) under Sec.  807.81(a)(3) because the device is about to be
significantly changed or modified, manufacturers must obtain 510(k)
clearance, among other relevant requirements, and demonstrate
compliance with the special controls included in the final order,
before marketing the new or changed device.

VI. Codification of Orders

    Sections 513(e) and 515(b), as amended by FDASIA, and 515(i) of the
FD&C Act require FDA to issue final orders rather than regulations to
reclassify devices. Therefore, FDA will continue to codify
reclassifications and requirements for approval of an application for
premarket approval, resulting from changes issued in final orders, in
the Code of Federal Regulations. Accordingly, under sections
513(e)(1)(A)(i) and 515(b) of the FD&C Act, as amended by FDASIA and
FDA's Medical Device Classification Procedures final rule (83 FR
64443), in this final order, we are codifying the amendment of Sec.
882.5800 by: (1) Revoking the requirements in Sec.  882.5800(b) and (c)
related to the classification of CES devices intended to treat anxiety
and/or insomnia as class III devices and codifying the reclassification
of CES devices intended to treat anxiety and/or insomnia to class II
(special controls); (2) retaining the requirements in Sec.  882.5800(b)
and (c) related to the classification of CES devices intended to treat
depression as class III devices subject to the requirement of approval
of an application for premarket approval, as described in section IV;
and (3) clarifying the device identification of CES devices to include
it as a prescription device.

VII. 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.

VIII. Paperwork Reduction Act of 1995

    This final order refers to previously approved collections of
information that are subject to review by the Office of Management and
Budget (OMB) under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C.
3501-3521). The collections of information in part 807,

subpart E, have been approved under OMB control number 0910-0120. The
collections of information in part 812 have been approved under OMB
control number 0910-0078. The collections of information in 21 CFR part
814, subparts A through E have been approved under OMB control number
0910-0231. The collections of information in part 801 have been
approved under OMB control number 0910-0485. The collections of
information in 21 CFR part 820 have been approved under OMB control
number 0910-0073.

IX. References

    The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 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. Transcript, February 10, 2012, meeting of the Neurological
Devices Panel of the Medical Device Advisory committee, available at
https://wayback.archive-it.org/7993/20170403223434/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM296891.pdf.
*2. FDA Executive Summary, Prepared for the February 10, 2012,
meeting of the Neurological Device Panel at https://wayback.archive-it.org/7993/20170404140724/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM290787.pdf.
*3. FDA, Reclassification of Daily Wear Spherical Contact Lenses
Consisting of Rigid Gas Permeable Plastic Materials; Withdrawal of
Proposed Rule. 48 FR 56778 to 56798, 1983.
*4. FDA Guidance, ``Use of Real-World Evidence to Support Regulatory
Decision-Making for Medical Devices,'' August 2017, available at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-evidence-support-regulatory-decision-making-medical-devices.
*5. Lande, R.G. and C. Gragnani, ``Efficacy of Cranial Electric
Stimulation for the Treatment of Insomnia: A Randomized Pilot
Study.'' Complementary Therapies in Medicine 21:8-13, 2012.
*6. Barclay, T.H. and R.D. Barclay, ``A Clinical Trial of Cranial
Electrotherapy Stimulation for Anxiety and Comorbid Depression.''
Journal of Affective Disorders 164:171-177, 2014.
*7. Rosenthal, S.H., ``Electrosleep: A Double-Blind cClinical
Study.'' Biological Psychiatry 4(2):179-185, 1972.
*8. Levitt, E.A., N. James, and P. Flavell, ``A Clinical Trial of
Electrosleep Therapy With a Psychiatric Inpatient Sample.''
Australian and New Zealand Journal of Psychiatry 9(4):287-290, 1975.
*9. Passini, F.G., C.G. Watson, and J. Herder, ``The Effects of
Cerebral Electric Therapy (electrosleep) on Anxiety, Depression, and
Hostility in Psychiatric Patients.'' Journal of Nervous and Mental
Disease 163(4):263-266, 1976.
*10. Scallet, A., R. Cloninger, and E. Othmer, ``The Management of
Chronic Hysteria: A Review and Double-Blind Trial of Electrosleep
and Other Relaxation Methods.'' Diseases of the Nervous System
37(6):347-353, 1976.
*11. Feighner, J.P., S.L. Brown, and J.E. Olivier, ``Electrosleep
Therapy: A Controlled Double Blind Study.'' Journal of Nervous and
Mental Disease 157(2):121-128, 1973.
*12. Hearst, E.D., C.R. Cloninger, E.L. Crews, and R.J. Cadoret,
``Electrosleep Therapy: A Double-Blind Trial.'' Archives of General
Psychiatry 30(4):463-466, 1974.
*13. Flemenbaum, A., ``Cerebral Electrotherapy (electrosleep): An
Open Clinical Study With a Six Month Follow Up.'' Psychosomatics
15(1):20-24, 1974.
*14. Rosenthal, S.H. and N.L. Wulfsohn, ``Electrosleep: A
Preliminary Communication.'' Journal of Nervous and Mental Disease
151(2):146-151, 1970.
*15. Matteson, M.T. and J.M. Ivancevich, ``An Exploratory
Investigation of CES as an Employee Stress Management Technique.''
Journal of Health and Human Resource Administration 9:93-109, 1986.
*16. Smith, R., ``Cranial Electrotherapy Stimulation in the
Treatment of Stress Related Cognitivie Dysfunction With an Eighteen
Month Follow-up.'' Journal of Cognitive Rehabilitation 17(6):14-18,
1999.
*17. Moore, J.A., C.S. Mellor, K.F. Standage, and H. Strong, ``A
Double Blind Study of Electrosleep for Anxiety and Insomnia.''
Biological Psychiatry 10(1):59-63, 1975.
*18. Marshall, A.G. and C.E. Izard, ``Cerebral Electrotherapeutic
Treatment of Depressions.'' Journal of Consulting and Clinical
Psychology 42(1):93-97, 1974.
*19. Kirsch, D., Ph.D., et al., ``Military Service Member and
Veteran Self Reports of Efficay of Cranial Electrotheraphy
Stimulation for Anxiety, Posttraumatic Stress Disorder, Insomnia,
and Depression.'' The United States Army Medical Journal, Oct.-Dec.
2014.
*20. Mellen, R.R. and W. Mackey, ``Reducing Sheriff's Officers'
Symptoms of Depression Using Cranial Electrotherapy Stimulation
(CES): A Control Experimental Study.'' The Correctional
Psychologist, 41(1):9-15, 2009.
*21. Lu, X.Y., A.H.Wang, Y. Li, J.S. Zhang, and B.X. Liu, ``Safety
and Effectiveness of Cranial Electrotherapy Stimulation in Treating
Children with Emotional Disorders.'' Chinese Journal of Clinical
Rehabilitation, 9(8):96-7, 2005.
*22. McClure, D. et al., ``A Pilot Study of Safety and Efficacy of
Cranial Electrotherapy Stimulation in Treatment of Bipolar II
Depression.'' The Journal of Nervous and Mental Disease, vol.
203(11):827-35, 2011.
*23. Chen, Y., Y. Lin, Z. Jiuping, L. Lejia, et al., ``Results of
Cranial Electrotherapy Stimulation to Children with Mixed Anxiety
and Depressive Disorder.'' Shanghai Archives of Psychiatry,
19(4):203-205, 2007.
*24. Jansson-Fr[ouml]jmark M., and K. Lindblom, ``A Bidirectional
Relationship Between Anxiety and Depression, and Insomnia? A
Prospective Study in the General Population.'' Journal Psychosomatic
Research, 64(4):443-9, April 2008.
*25. Coplan J.D., C.J. Aaronson, V. Panthangi, and Y. Kim,
``Treating Comorbid Anxiety and Depression: Psychosocial and
Pharmacological Approaches.'' World Journal of Psychiatry, 5(4):366-
78, Dec. 2015.
*26. Bystritsky, A., L. Kerwin, and J. Feusner, ``A Pilot Study of
Cranial Electrotherapy Stimulation for Generalized Anxiety
Disorder.'' Journal of Clinical Psychiatry, 69(3):412-417, March
2008.
*27. Yennurajalingam, S., D.H. Kang, W.J. Hwu, N.S. Padhye, et al.,
``Cranial Electrotherapy Stimulation for the Management of
Depression, Anxiety, Sleep Disturbance, and Pain in Patients With
Advanced Cancer: A Preliminary Study.'' Journal of Pain and Symptom
Management, 55(2):198-206, Feb. 2018.
    *28. Bhardwaj, M., N. Arumugam, and S. Gambhir, ``Efficacy of
Cranial Electrical Stimulation and Rational Emotive Behavior Therapy
in Improving Psychological Illness among Chronic Stroke Survivors: A
Pilot Randomized Controlled Trial.'' Annals of Indian Academy of
Neurology, 21(3):188-192, Jul.-Sept. 2018.
    *29. Gong, B.Y., H.M. Ma, X.Y. Zang, S.Y. Wang, et al.,
``Efficacy of Cranial Electrotherapy Stimulation Combined with
Biofeedback Therapy in Patients with Functional Constipation.''
Journal of Neurogastroenterol Motility, 22(3):497-508, July 2016.
    30. Lande, R.G. and C.T. Gragnani, ``Prospective Study of Brain
Wave Changes Associated With Cranial Electrotherapy Stimulation.''
The Primary Care Companion for CNS Disorders, 18;20(1), Jan. 2018,
available at https://www.psychiatrist.com/PCC/article/Pages/2018/v20n01/17m02214.aspx.
    31. American Psychiatric Association, Diagnostic and Statistical
Manual of Mental Disorders (5th ed.). Arlington, VA, 2013.
    *32. FDA Guidance, ``Procedures for Meetings of the Medical
Devices Advisory Committee,'' September 2017, available at

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/procedures-meetings-medical-devices-advisory-committee.
    *33. FDA Guidance, ``Public Availability of Advisory Committee
Members' Financial Interest Information and Waivers,'' March 2014,
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/public-availability-advisory-committee-members-financial-interest-information-and-waivers.

List of Subjects in 21 CFR Part 882

    Medical devices, Neurological devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
882 is amended as follows:

PART 882--NEUROLOGICAL DEVICES

0
1. The authority citation for part 882 continues to read as follows:

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

0
2. Revise Sec.  882.5800 to read as follows:

Sec.  882.5800  Cranial electrotherapy stimulator.

    (a) Identification. A cranial electrotherapy stimulator is a
prescription device that applies electrical current that is not
intended to induce a seizure to a patient's head to treat psychiatric
conditions.
    (b) Classification. (1) Class II (special controls) when intended
to treat insomnia and/or anxiety. The special controls for this device
are:
    (i) A detailed summary of the clinical testing pertinent to use of
the device to demonstrate the effectiveness of the device to treat
insomnia and/or anxiety.
    (ii) Components of the device that come into human contact must be
demonstrated to be biocompatible.
    (iii) The device must be designed and tested for electrical safety
and electromagnetic compatibility (EMC) in its intended use
environment.
    (iv) Appropriate software verification, validation, and hazard
analysis must be performed.
    (v) The technical parameters of the device, including waveform,
output mode, pulse duration, frequency, train delivery, maximum charge,
and energy, must be fully characterized and verified.
    (vi) The labeling for the device must include the following:
    (A) The intended use population and the intended use environment;
    (B) A warning that patients should be monitored by their physician
for signs of worsening;
    (C) A warning that instructs patients on how to mitigate the risk
of headaches, and what to do should a headache occur;
    (D) A warning that instructs patients on how to mitigate the risk
of dizziness, and what to do should dizziness occur;
    (E) 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;
    (F) Instructions for use that address where to place the
electrodes, what stimulation parameters to use, and duration and
frequency of treatment sessions. This information must be based on the
results of clinical studies for the device;
    (G) A detailed summary of the device technical parameters,
including waveform, output mode, pulse duration, frequency, train
delivery, and maximum charge and energy; and
    (H) Information on validated methods for reprocessing any reusable
components between uses.
    (vii) Cranial electrotherapy stimulator devices marketed prior to
the effective date of this reclassification must have an amendment
submitted to the previously cleared premarket notification (510(k))
demonstrating compliance with these special controls.
    (2) Class III (premarket approval) when intended to treat
depression.
    (c) Date premarket approval application (PMA) or notice of
completion of product development protocol (PDP) is required. A PMA or
notice of completion of a PDP is required to be filed with the Food and
Drug Administration on or before March 19, 2020, for any cranial
electrotherapy stimulator device with an intended use described in
paragraph (b)(2) of this section, that was in commercial distribution
before May 28, 1976, or that has, on or before March 19, 2020, been
found to be substantially equivalent to any cranial electrotherapy
stimulator device with an intended use described in paragraph (b)(2) of
this section, that was in commercial distribution before May 28, 1976.
Any other cranial electrotherapy stimulator device with an intended use
described in paragraph (b)(2) of this section shall have an approved
PMA or declared completed PDP in effect before being placed in
commercial distribution.

    Dated: December 13, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-27295 Filed 12-19-19; 8:45 am]
BILLING CODE 4164-01-P


[Federal Register: October 7, 2009 (Volume 74, Number 193)]
[Notices]
[Page 51641-51643]
[DOCID:fr07oc09-112]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-60752; File No. SR-NYSE-2009-101]

Self-Regulatory Organizations; New York Stock Exchange LLC;
Notice of Filing and Immediate Effectiveness of Proposed Rule Change
Extending the Pilot Period To Receive Inbound Routes of Orders From
Archipelago Securities LLC

September 30, 2009.
    Pursuant to Section 19(b)(1) \1\ of the Securities Exchange Act of
1934 (the

``Act'') and Rule 19b-4 thereunder,\2\ notice is hereby given that, on
September 30, 2009, New York Stock Exchange LLC (``NYSE'' or the
``Exchange'') filed with the Securities and Exchange Commission (the
``Commission'') the proposed rule change as described in Items I and
II, below, which Items have been prepared by the self-regulatory
organization. The Commission is publishing this notice to solicit
comments on the proposed rule change from interested persons.
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    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
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I. Self-Regulatory Organization's Statement of the Terms of Substance
of the Proposed Rule Change

    The Exchange proposes to extend the pilot period of the Exchange's
prior approvals to receive inbound routes of certain equities orders
from Archipelago Securities LLC (``Arca Securities''), an NYSE
affiliated member. The text of the proposed rule change is available at
the Exchange, the Commission's Public Reference Room, and http://
www.nyse.com.

II. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    In its filing with the Commission, the self-regulatory organization
included statements concerning the purpose of, and basis for, the
proposed rule change and discussed any comments it received on the
proposed rule change. The text of those statements may be examined at
the places specified in Item IV below. The Exchange has prepared
summaries, set forth in sections A, B, and C below, of the most
significant parts of such statements.

A. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

1. Purpose
    Currently, Arca Securities is the approved outbound order routing
facility of the Exchange.\3\ Arca Securities is also the approved
outbound order routing facility of NYSE Arca and NYSE Amex LLC (``NYSE
Amex'').\4\ The Exchange has also been previously approved to receive
inbound routes of equities orders by Arca Securities in its capacity as
an order routing facility of NYSE Arca and NYSE Amex.\5\ The Exchange's
authority to receive inbound routes of equities orders by Arca
Securities was subject to a pilot period ending September 29, 2009. The
Exchange hereby seeks to extend the previously approved pilot period
(with the attendant obligations and conditions) for an additional 3
months, through December 31, 2009.
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    \3\ See Securities Exchange Act Release No. 34-55590 (April 5,
2007), 72 FR 18707 (April 13, 2007) (notice of immediate
effectiveness of SR-NYSE-2007-29); see also, Securities and Exchange
Act Release No. 34-58680 (September 29, 2008), 73 FR 58283 (October
6, 2008) (order approving SR-NYSE-2008-76).
    \4\ See Securities Exchange Act Release No. 34-53238 (July 28,
2006), 71 FR 44758 (August 7, 2006) (order approving SR-NYSEArca-
2006-13); see also, Securities Exchange Act Release No. 52497
(September 22, 2005), 70 FR 56949 (September 29, 2005) (SR-PCX-2005-
90); see also, Securities Exchange Act Release No. 44983 (October
25, 2001), 66 FR 55225 (November 1, 2001) (SR-PCX-00-25); see also,
Securities Exchange Act Release No. 58681 (September 29, 2008), 73
FR 58285 (October 6, 2008) (order approving NYSEArca-2008-90). See
Securities Exchange Act Release No. 59009 (November 24, 2008), 73 FR
73363 (December 2, 2008) (order approving SR-NYSEALTR-2008-07); see
also, Securities and Exchange Act Release No. 34-59473 (February 27,
2009), 74 FR 9853 (March 6, 2009) (order approving SR-NYSEALTR-2009-
18).
    \5\ See Securities and Exchange Act Release No. 34-58680
(September 29, 2008), 73 FR 58283 (October 6, 2008) (order approving
SR-NYSE-2008-76); see Securities Exchange Act Release No. 59011
(November 24, 2008), 73 FR 73360 (December 2, 2008) (order approving
SR-NYSE-2008-122); see also Securities and Exchange Act Release No.
60255 (July 7, 2009), 74 FR 34065 (July 14, 2009) (order approving
SR-NYSE-2009-58).
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2. Statutory Basis
    The proposed rule change is consistent with Section 6(b) \6\ of the
Securities Exchange Act of 1934 (the ``Act''), in general, and furthers
the objectives of Section 6(b)(5) \7\ in particular in that it is
designed to prevent fraudulent and manipulative acts and practices, to
promote just and equitable principles of trade, to foster cooperation
and coordination with persons engaged in facilitating transactions in
securities, and to remove impediments to and perfect the mechanism of a
free and open market and a national market system. Specifically, the
proposed rule change will allow the Exchange to continue receiving
inbound routes of equities orders from Arca Securities acting in its
capacity as a facility of the NYSE Arca and NYSE Amex, in a manner
consistent with prior approvals and established protections. The
Exchange believes that extending the previously approved pilot period
for three months is of sufficient length to permit both the Exchange
and the Commission to assess the impact of the Exchange's authority to
receive direct inbound routes of equities orders via Arca Securities
(including the attendant obligations and conditions).
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    \6\ 15 U.S.C. 78f(b).
    \7\ 15 U.S.C. 78f(b)(5).
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B. Self-Regulatory Organization's Statement on Burden on Competition

    The Exchange does not believe that the proposed rule change will
impose any burden on competition that is not necessary or appropriate
in furtherance of the purposes of the Act.

C. Self-Regulatory Organization's Statement on Comments on the Proposed
Rule Change Received From Members, Participants, or Others

    No written comments were solicited or received with respect to the
proposed rule change.

III. Date of Effectiveness of the Proposed Rule Change and Timing for
Commission Action

    Because the foregoing rule change does not: (1) Significantly
affect the protection of investors or the public interest; (2) impose
any significant burden on competition; and (3) become operative for 30
days after the date of this filing, or such shorter time as the
Commission may designate, it has become effective pursuant to Section
19(b)(3)(A) of the Act \8\ and Rule 19b-4(f)(6) thereunder.\9\
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    \8\ 15 U.S.C. 78s(b)(3)(A).
    \9\ 17 CFR 240.19b-4(f)(6).
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    A proposed rule change filed under 19b-4(f)(6) normally may not
become operative prior to 30 days after the date of filing.\10\
However, Rule 19b-4(f)(6)(iii) \11\ permits the Commission to designate
a shorter time if such action is consistent with the protection of
investors and the public interest. The Exchange has requested that the
Commission waive the 30-day operative delay. The Exchange notes that
the proposal will allow the Exchange to continue receiving inbound
routes of equities orders from Arca Securities, in a manner consistent
with prior approvals and established protections, while also permitting
the Exchange and the Commission to assess the impact of the pilot.\12\
The Commission believes that waiving the 30-day operative delay is
consistent with the protection of investors and the public interest
because such waiver would allow the pilot period to be extended without
interruption through December 31, 2009. For this reason, the Commission

designates the proposed rule change to be operative upon filing with
the Commission.\13\
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    \10\ 17 CFR 240.19b-4(f)(6)(iii). In addition, Rule 19b-
4(f)(6)(iii) requires that a self-regulatory organization submit to
the Commission written notice of its intent to file the proposed
rule change, along with a brief description and text of the proposed
rule change, at least five business days prior to the date of filing
of the proposed rule change, or such shorter time as designated by
the Commission. The Exchange has satisfied this requirement.
    \11\ Id.
    \12\ See SR-NYSE-2009-101, Item 7.
    \13\ For the purposes only of waiving the 30-day operative
delay, the Commission has considered the proposed rule's impact on
efficiency, competition, and capital formation. See 15 U.S.C.
78c(f).
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    At any time within 60 days of the filing of such proposed rule
change the Commission may summarily abrogate such rule change if it
appears to the Commission that such action is necessary or appropriate
in the public interest, for the protection of investors or otherwise in
furtherance of the purposes of the Act.

IV. Solicitation of Comments

    Interested persons are invited to submit written data, views, and
arguments concerning the foregoing, including whether the proposed rule
change is consistent with the Act. Comments may be submitted by any of
the following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://
www.sec.gov/rules/sro.shtml); or
     Send an e-mail to<EMAIL_ADDRESS>Please include
File Number SR-NYSE-2009-101 on the subject line.

Paper Comments

     Send paper comments in triplicate to Elizabeth M. Murphy,
Secretary, Securities and Exchange Commission, 100 F Street, NE.,
Washington, DC 20549-1090.

All submissions should refer to File Number SR-NYSE-2009-101. This file
number should be included on the subject line if e-mail is used. To
help the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's Internet Web site (http://www.sec.gov/rules/
sro.shtml). Copies of the submission, all subsequent amendments, all
written statements with respect to the proposed rule change that are
filed with the Commission, and all written communications relating to
the proposed rule change between the Commission and any person, other
than those that may be withheld from the public in accordance with the
provisions of 5 U.S.C. 552, will be available for inspection and
copying in the Commission's Public Reference Room on official business
days between the hours of 10 a.m. and 3 p.m. Copies of such filing also
will be available for inspection and copying at the principal office of
the Exchange. All comments received will be posted without change; the
Commission does not edit personal identifying information from
submissions. You should submit only information that you wish to make
available publicly. All submissions should refer to File Number SR-
NYSE-2009-101 and should be submitted on or before October 28, 2009.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\14\
Florence E. Harmon,
Deputy Secretary.
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    \14\ 17 CFR 200.30-3(a)(12).
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[FR Doc. E9-24081 Filed 10-6-09; 8:45 am]

BILLING CODE 8011-01-P