[Federal Register Volume 80, Number 249 (Tuesday, December 29, 2015)]
[Proposed Rules]
[Pages 81223-81233]
[FR Doc No: 2015-32592]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 882

[Docket No. FDA-2014-N-1210]

Neurological Devices; Reclassification of Electroconvulsive
Therapy Devices Intended for Use in Treating Severe Major Depressive
Episode in Patients 18 Years of Age and Older Who Are Treatment
Resistant or Require a Rapid Response; Effective Date of Requirement
for Premarket Approval for Electroconvulsive Therapy for Certain
Specified Intended Uses

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed order.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a proposed
administrative order to reclassify the electroconvulsive therapy (ECT)
device for use in treating severe major depressive episode (MDE)
associated with major depressive disorder (MDD) or bipolar disorder
(BPD) in patients 18 years of age and older who are treatment-resistant
or who require a rapid response due to the severity of their
psychiatric or medical condition, which is a preamendments class III
device, into class II (special controls) based on new information. FDA
is also proposing to require the filing of a premarket approval
application (PMA) or a notice of completion of a product development
protocol (PDP) for ECT devices for other intended uses specified in
this proposed order. The Agency is also summarizing its proposed
findings regarding the degree of risk of illness or injury designed to
be eliminated or reduced by requiring the devices to meet the statute's
approval requirements for other intended uses specified in this
proposed order. In addition, FDA is announcing the opportunity for
interested persons to request that the Agency change the classification
of any of the devices mentioned in this document based on new
information. This action implements certain statutory requirements.

DATES: Submit either electronic or written comments on this proposed
order by March 28, 2016. See section XVII of this document for the
proposed effective date of a final order based on this proposed order.

ADDRESSES: You may submit comments as follows:

Electronic Submissions
    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, 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.
2014-N-1210 for ``Neurological Devices; Reclassification of
Electroconvulsive Therapy Devices Intended for Use in Treating Severe
Major Depressive Episode in Patients 18 Years of Age and Older Who Are
Treatment-Resistant or Require a Rapid Response; Effective Date of
Requirement for Premarket Approval for Electroconvulsive Therapy
Devices for Certain Specified Intended Uses''. Received comments will
be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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 http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Michael J. Ryan, Center for Devices
and

Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1615, Silver Spring, MD 20993,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L.
94-295), the Safe Medical Devices Act of 1990 (SMDA) (Pub. L. 101-629),
Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L.
105-115), the Medical Device User Fee and Modernization Act of 2002
(MDUFMA) (Pub. L. 107-250), the Medical Devices Technical Corrections
Act (Pub. L. 108-214), the Food and Drug Administration Amendments Act
of 2007 (Pub. L. 110-85), and the Food and Drug Administration Safety
and Innovation Act (FDASIA) (Pub. L. 112-144), 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). One type of general control provided by the FD&C Act is a
restriction on the sale, distribution, or use of a device under section
520(e) of the FD&C Act (21 U.S.C. 360j(e)). A restriction under section
520(e) of the FD&C Act must be implemented through rulemaking
procedures, unlike the administrative order procedures that apply to
this proposed reclassification under section 513(e) of the FD&C Act, as
amended by FDASIA.
    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 regulation
classifying the device; and (3) published a final regulation
classifying the device. FDA has classified most preamendments devices
under these procedures.
    Devices that were not in commercial distribution prior to May 28,
1976 (generally referred to as postamendments devices) are
automatically classified by section 513(f) 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, 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).
    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 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 or until the device is
subsequently reclassified into class I or class II.
    Although, under the FD&C Act, the 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. For simplicity,
although corresponding requirements for PDPs remain available to
manufacturers in response to a final order under section 515(b) of the
FD&C Act, this document will refer only to the requirement for the
filing and receiving approval of a PMA.
    On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA (126
Stat. 1056) amended section 513(e) of the FD&C Act, changing the
process for reclassifying a device from rulemaking to an administrative
order. Section 608(b) of FDASIA amended section 515(b) of the FD&C Act
changing the process for requiring premarket approval for a
preamendments class III device from rulemaking to an administrative
order.

A. Reclassification

    FDA is publishing this document to propose the reclassification of
ECT devices for use in treating severe MDE associated with MDD or BPD
in patients 18 years of age and older who are treatment-resistant or
who require a rapid response due to the severity of their psychiatric
or medical condition from class III to class II.
    Section 513(e) of the FD&C Act governs reclassification of
classified preamendments devices. This section provides that FDA may,
by administrative order, reclassify a device based upon ``new
information.'' FDA can initiate a reclassification under section 513(e)
of the FD&C Act or an interested person may petition FDA to reclassify
a preamendments device. The term ``new information,'' as used in
section 513(e) of the FD&C Act, includes information developed as a
result of a reevaluation of the data before the Agency when the device
was originally classified, as well as information not presented, not
available, or not developed at that time. (See, e.g., Holland Rantos
Co. v. United States Department of Health, Education, and Welfare, 587
F.2d 1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944
(6th Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).)
    Reevaluation of the data previously before the Agency is an
appropriate basis for subsequent regulatory action where the
reevaluation is made in light of newly available regulatory authority
(see Bell, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 F. Supp. 382,
388-391 (D.D.C. 1991)) or in light of changes in ``medical science''
(see Upjohn, 422 F.2d at 951). Whether data before the Agency are old
or new data, the ``new information'' to support reclassification under
section 513(e) 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 Mfrs. Assoc. v. FDA, 766 F.2d 592 (D.C.
Cir. 1985), cert. denied, 474 U.S. 1062 (1986).)
    FDA relies upon ``valid scientific evidence'' 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 .) Section 520(h)(4) of the
FD&C Act, added by FDAMA, provides that FDA may use, for
reclassification of a device, certain information in a PMA 6 years
after the application has been approved. 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.

    Section 513(e)(1) of the FD&C Act sets forth the process for
issuing a final order for reclassifying a device. Specifically, prior
to the issuance of a final order reclassifying a 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 to a
public docket. FDA has held a meeting of a device classification panel
described in section 513(b) of the FD&C Act with respect to ECT
devices, and therefore, has met this requirement under section
515(b)(1) of the FD&C Act.
    FDAMA added a section 510(m) to the FD&C Act. 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 assure the safety and effectiveness of the device.

B. Requirement for Premarket Approval Application

    FDA is proposing to require PMAs for ECT devices for the intended
uses listed in section IX of this proposed order. For the purposes of
this proposed order, the term, ``Certain Specified Intended Uses,''
refers to the listing of the intended uses in section IX of this
proposed order and includes the following: schizophrenia, bipolar manic
states, schizoaffective disorder, schizophreniform disorder, and
catatonia.
    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, payors, and providers. FDA has held a
meeting of a device classification panel described in section 513(b) of
the FD&C Act with respect to ECT devices, and therefore, has met this
requirement under section 515(b)(1) of the FD&C Act.
    Section 515(b)(2) of the FD&C Act provides that a proposed order to
require premarket approval shall contain: (1) The proposed order, (2)
proposed findings with respect to the degree of risk of illness or
injury designed to be eliminated or reduced by requiring the device to
have an approved PMA or a declared completed PDP and the benefit to the
public from the use of the device, (3) an opportunity for the
submission of comments on the proposed order and the proposed findings,
and (4) an opportunity to request a change in the classification of the
device based on new information relevant to the classification of the
device.
    Section 515(b)(3) of the FD&C Act provides that FDA shall, after
the close of the comment period on the proposed order, consideration of
any comments received, and a meeting of a device classification panel
described in section 513(b) of the FD&C Act, issue a final order to
require premarket approval or publish a document terminating the
proceeding together with the reasons for such termination. If FDA
terminates the proceeding, FDA is required to initiate reclassification
of the device under section 513(e) of the FD&C Act, unless the reason
for termination is that the device is a banned device under section 516
of the FD&C Act (21 U.S.C. 360f).
    Under section 501(f) of the FD&C Act (21 U.S.C. 351(f)), 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. For ECT devices, the preamendments class III
devices that are the subject of this proposal, the later of these two
time periods is the 90-day period. Since these devices were classified
in 1979, the 30-month period has expired (44 FR 51776, September 4,
1979). Therefore, if the proposal to require premarket approval for ECT
devices for Certain Specified Intended Uses is finalized, section
501(f)(2)(B) of the FD&C Act requires that a PMA for such device be
filed within 90 days of the date of issuance of the final order. If a
PMA is not filed for such device within 90 days after the issuance of a
final order, the device would be deemed adulterated under section
501(f) of the FD&C Act.
    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 part 812 (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. 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 by the later
of the two dates, 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. 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). In the past, FDA has requested that manufacturers take
action to prevent the further use of devices for which no PMA has been
filed and may determine that such a request is appropriate for the
class III devices that are the subject of this proposed order, if
finalized.
    In accordance with section 515(b)(2)(D) of the FD&C Act, interested
persons are being offered the opportunity to request reclassification
of ECT devices for Certain Specified Intended Uses.

II. Regulatory History of the Device

    In the preamble to the proposed rule (43 FR 55729, November 28,
1978), FDA described the recommendation of the Neurological Device
Classification Panel (the Panel) that ECT be classified into class II
because: ``Although the use of this device involves a substantial risk
to the patient, the Panel believes that the benefit of the treatment
outweighs the risks involved if the patients are selected carefully and
the devices are designed and used properly. The Panel believes that a
standard will provide reasonable assurance of the safety and
effectiveness of the device and that there is sufficient information to
establish a standard to provide such assurance.'' However, in 1979 (44
FR 51776, September 4, 1979), FDA classified ECT into class III after
receiving several comments on the proposed rule, and reconvening the
Panel to discuss these comments (May 29, 1979). The Panel discussed
whether there was sufficient evidence to establish a performance
standard for ECT. Several panel members expressed doubt that such
information was available, and the Panel voted to recommend that ECT be
classified into class III. FDA agreed with the Panel stating that FDA
did not believe that the characteristics of ECT devices had been

identified precisely enough such that special controls could be
established that would provide reasonable assurance of the safety and
effectiveness of the device.
    On August 13, 1982, the American Psychiatric Association (APA)
submitted a reclassification petition to FDA requesting that ECT be
classified into class II. The reclassification petition was discussed
at a Panel meeting on November 4, 1982 (47 FR 44611, October 8, 1982).
The Panel recommended that ECT be reclassified from class III to class
II. FDA tentatively agreed that there was sufficient evidence to
reclassify to class II for severe depression and schizophrenia and
published a notice of intent to reclassify (48 FR 14758, April 5,
1983). Several comments received by the Agency argued that research and
data did not support that ECT is an effective therapy for
schizophrenia, and after careful review of the scientific literature
and the APA's petition, FDA agreed with the comments. In the subsequent
proposed rule (55 FR 36578, September 5, 1990), FDA determined that the
evidence of effectiveness for schizophrenia was inconclusive, and
proposed that ECT be reclassified to class II only for severe
depression and remain class III for all other indications. In 1995, FDA
published an order for the submission of safety and effectiveness
information on ECT devices (60 FR 41986, August 14, 1995). In 2003, FDA
published an intent to withdraw the 1990 proposed rule (68 FR 19766,
April 22, 2003) followed by withdrawal in 2004 (69 FR 68831, November
26, 2004) of the proposed rule for reclassification of ECT, along with
other FDA proposed rules that had been outstanding for more than 5
years because the proposals were no longer considered viable candidates
for final action. Thus, ECT devices remain in class III for all
indications.
    In 2009, FDA published an order for the submission of safety and
effectiveness information on ECT devices by August 7, 2009 (74 FR
16214, April 9, 2009). In response to that order, FDA received two
submissions from ECT manufacturers suggesting that ECT devices could be
reclassified to class II. The manufacturers stated that safety and
effectiveness of these devices may be assured by reducing the frequency
of treatments, temporary or permanent interruption of treatments,
reduction of stimulus dose, electrode placement, dosage or type of
anesthetic (or other) medications, including minimizing psychotropic
medications, brief pulse or ultra-brief pulse waveform stimulus, EEG
monitoring, proper preparation (including conductive gel) and contact
of the electrodes to the skin, changing anesthetic medications or
doses, and changing concurrent medications.
    In 2009, FDA also opened a public docket to receive information and
comments regarding the current classification process for ECT by
January 8, 2010 (74 FR 46607, September 10, 2009). FDA received over
3,000 submissions to the docket, with the majority of respondents,
approximately 80 percent, opposing reclassification of ECT. The
majority of those opposing reclassification of ECT cited adverse events
from ECT treatment as the basis for their opposition. The most common
type of adverse event mentioned in the public docket were memory
adverse events, followed by other cognitive complaints, brain damage,
and death.
    On January 27-28, 2011, a meeting of the Neurological Devices Panel
was held to discuss the classification of ECT devices for treatment of
several disorders. There was panel consensus recommending class III for
Schizophrenia, Bipolar manic states, Schizoaffective, and
Schizophreniform disorder. The Panel did not reach consensus on the
classification of ECT for depression (unipolar and bipolar) and
catatonia. The Panel transcript and other meeting materials are
available on FDA's Web site (http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/ucm240924.htm).

III. Device Description

    The ECT device consists of an electrical generator and a pair of
electrodes that apply a brief intense electrical current to the head in
order to induce a generalized seizure. In addition to generating and
modulating the electrical functions of the stimulus, the box enclosing
the generator also has capabilities and displays for physiological
monitoring. The device parameters such as voltage, pulse width,
frequency, and treatment (train) duration are adjustable. The typical
display may provide information such as Electroencephalograph (EEG)
activity, stimulus administration, total charge, energy, and impedance.
These devices are currently regulated under Sec.  882.5940 (21 CFR
882.5940), product code GXC.
    FDA is proposing in this order to modify the identification
language from how it is presently written in Sec.  882.5940(a). FDA is
clarifying in the identification that these are prescription devices
and clarifying that this device type includes the ECT pulse generator
and its stimulation electrodes and accessories.

IV. Proposed Reclassification

    FDA is proposing that ECT devices intended for treating severe MDE
associated with MDD and BPD in patients 18 years of age and older who
are treatment-resistant or who require a rapid response due to the
severity of their psychiatric or medical condition be reclassified from
class III to class II. In this proposed order, the Agency has
identified special controls under section 513(a)(1)(B) of the FD&C Act
that, together with general controls applicable to the devices, would
provide reasonable assurance of safety and effectiveness. Absent the
special controls identified in this proposed order, general controls
applicable to the device are insufficient to provide reasonable
assurance of the safety and effectiveness of the device.
    Therefore, in accordance with sections 513(e) and 515(i) of the
FD&C Act and21 CFR 860.130, based on new information with respect to
the devices and taking into account the public health benefit of the
use of the device and the nature and known incidence of the risk of the
device, FDA, on its own initiative, is proposing to reclassify this
preamendments class III device into class II when the device is
intended to treat severe MDE associated with MDD and BPD in patients 18
years of age and older who are treatment-resistant or who require a
rapid response due to the severity of their psychiatric or medical
condition. FDA believes that this new information is sufficient to
demonstrate that the proposed special controls can effectively mitigate
the risks to health identified in the next section, and that these
special controls, together with general controls, will provide a
reasonable assurance of safety and effectiveness for ECT devices
intended for treating severe MDE associated with MDD and BPD in
patients 18 years of age and older who are treatment-resistant or who
require a rapid response due to the severity of their psychiatric or
medical condition.
    Section 510(m) of the FD&C Act authorizes the Agency to exempt
class II devices from premarket notification (510(k)) submission. FDA
has considered ECT devices intended for treating severe MDE associated
with MDD and BPD in patients 18 years of age and older who are
treatment-resistant or who require a rapid response due to the severity
of their psychiatric or medical condition and decided that the device
does require premarket notification. Therefore, the Agency does not
intend to exempt this

proposed class II device from premarket notification (510(k))
submission.

V. Risks to Health

    After considering the available information from the reports and
recommendations of the advisory committees (panels) for the
classification of these devices, FDA has evaluated the risks to health
associated with the use of ECT devices and determined that the
following risks to health are associated with its use:
     Adverse reaction to anesthetic agents/neuromuscular
blocking agents. The muscle relaxing and sedating (or sleep inducing)
drugs that are a part of the procedure may hamper the patient's ability
to breathe spontaneously.
     Adverse skin reactions. The patient-contacting materials
of the device may cause an adverse immunological or allergic reaction
in a patient.
     Cardiovascular complications. The therapeutic convulsions
may be accompanied by arrhythmias (irregular heartbeat) or ischemia/
infarction (i.e., heart attack). Hypertension (high blood pressure) as
well as hypotension (low blood pressure) may be associated with ECT
treatment. ECT treatment may also result in stroke (impairment of blood
flow to the brain or bleeding in the brain).
     Cognition and memory impairment. ECT treatment may result
in memory impairment, specifically immediate post-treatment
disorientation, anterograde memory impairment and retrograde personal
(autobiographical) memory impairment.
     Death. Death may result from various complications of ECT
such as reactions to anesthesia, cardiovascular complications,
pulmonary complications, or stroke.
     Dental/oral trauma. Dental fractures, dislocations,
lacerations, and prosthetic damage may occur as a result of strong
muscle contractions during treatment.
     Device malfunction. Faulty hardware, software or
accessories (electrodes) or improper use may cause electrical hazards,
such as the risk of excessive dose administration, prolonged seizures,
and skin burns.
     Manic symptoms. ECT treatment may result in the
development of hypomanic or manic symptoms.
     Pain/discomfort. The patient may experience mild to
moderate pain following the motor seizure induced by ECT treatment.
     Physical trauma. Inadequate supportive drug treatment may
allow the patient to be injured from unconscious violent movements
during convulsions.
     Prolonged or tardive seizures. ECT treatment may result in
prolonged or delayed seizures, and status epilepticus (continuous
unremittent seizure) may ensue if prolonged seizures are not properly
treated.
     Pulmonary complications. ECT treatment may result in
prolonged apnea (no breathing) or inhalation of foreign material, such
as regurgitated stomach contents.
     Skin burns. Excessive electrical current or improperly
designed electrodes may cause the patient's skin under the electrodes
to be burned.
     Worsening of psychiatric symptoms. ECT treatment may be
ineffective and therefore may result in worsening psychiatric symptoms.

VI. Summary of Reasons for Reclassification

    FDA believes that ECT devices indicated for severe MDE associated
with MDD and BPD in patients 18 years of age and older who are
treatment-resistant or who require a rapid response due to the severity
of their psychiatric or medical condition should be reclassified from
class III to class II because, in light of new information about the
effectiveness of these devices, special controls, in addition to
general controls, can be established to provide reasonable assurance of
safety and effectiveness of the device, and because general controls
themselves are insufficient to provide reasonable assurance of its
safety and effectiveness. FDA believes that in the specified patient
population, and with the application of general and special controls as
described in this document, the probable benefit to health from use of
the device outweighs the probable injury or illness from such use. FDA
acknowledges significant risks associated with ECT but believes that
for the specified population--patients age 18 years of age and older
experiencing a severe MDE associated with MDD or BPD for whom other
treatment options have not been successful or for whom rapid,
definitive response is needed due the severity of a psychiatric or
medical condition--the probable benefit of ECT outweighs these risks.
FDA is inviting comments on whether the term ``treatment resistant''
and the phrase ``require rapid response'' provide sufficient clarity to
the population for which ECT benefits outweigh risks.

VII. Summary of Data Upon Which the Reclassification Is Based

    Since the time of the original ECT device classification,
sufficient evidence has been developed to support a reclassification of
ECT to class II with special controls for severe MDE associated with
MDD and BPD in patients 18 years of age and older who are treatment-
resistant or who require a rapid response due to the severity of their
psychiatric or medical condition. FDA's review of the clinical
literature has been previously summarized in the Executive Summary to
the January 27-28, 2011, Neurological Device Panel meeting to discuss
ECT classification (http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM240933.pdf). The largest body of evidence for ECT effectiveness
exists for MDE associated with MDD and BPD in patients 18 years of age
and older. Based on this review, FDA concluded that ECT demonstrated
effectiveness in the acute phase (less than 3 months after treatment);
however, the Panel members had various scientific opinions regarding
the long-term effectiveness of ECT for the treatment of depression, but
agreed that it was effective in the acute phase. Panel members
indicated that controlled clinical trials are lacking regarding the
effectiveness of ECT beyond the acute phase, in part, due to the fact
that many patients have an initial improvement in the depressive
symptoms following an acute course of ECT and are able to return to
alternative treatments for managing depression such as medications and
psychotherapy. The findings from FDA's review are consistent with other
recently conducted, comprehensive, high quality systematic reviews,
including the American Psychiatric Association (APA) recommendations/
guidelines (Ref. 1), the Third report of the Royal College of
Psychiatrists' Special Committee on ECT (2004) (Ref. 2), the United
Kingdom National Institute for Health and Clinical Excellence (NICE
2003; NICE 2009) (Refs. 3, 4), the Surgeon General's report on mental
health (Ref. 5), systematic reviews by Semkovska and McLoughlin (Ref.
6), and Greenhalgh et al (Ref. 7). These findings from the FDA review
included examining the results of over 60 randomized controlled
clinical trials comparing ECT with either placebo (sham) or
antidepressant therapy in which ECT was superior for patients with MDD
and BPD in patients 18 years of age and older who are treatment-
resistant or who require a rapid response due to the severity of their
psychiatric or medical condition. In addition, FDA conducted a
systematic meta-analysis of these

studies which supported a robust effect of ECT in the short-term (e.g.
3 months) (Ref. 11).
    FDA also examined other conditions, including bipolar mania,
schizophrenia, schizoaffective disorder, schizophreniform disorder, and
catatonia, but there were insufficient clinical data to support
effectiveness for these conditions. FDA relied upon literature
describing clinical study data collected largely in patients age 18 and
older. Data on the use of ECT in children and adolescents is limited
and hence the recommended reclassification is limited to patients 18
years of age and older. Most of the published literature FDA is aware
of and reviewed focused on subject populations that did not receive
benefit from prior treatments; therefore, the recommended
reclassification is limited to treatment resistant populations as well
as those patients who require a rapid response due to the severity of
their psychiatric or medical condition. Further, practice guidelines
published by the APA task force on ECT and the NICE in the United
Kingdom recommend that ECT be considered for primary use (i.e., prior
to medications) when there is a need for rapid, definitive response due
to the severity of a psychiatric or medical condition. Conventional
treatments such as medications and psychotherapy are likely to be less
effective for a rapid definitive response, thus the recommended
reclassification for ECT includes patients who require a rapid response
because of the severity of their psychiatric or medical condition.
    Panel deliberations focused heavily on ECT versus sham meta-
analysis for treatment of depression. Discussion focused on the
clinical meaningfulness of the effect size, the wide confidence
interval which included 0 (i.e., the possibility of no effect), and the
sources of variability in the dataset. Compared with other approved
treatments for depression, the data suggest that the effect size of ECT
is at least as large as, or larger than, that of other treatments
(i.e., antidepressant medications) (Refs. 8, 9). In addition, other
sources of evidence supported the effectiveness claim of ECT, including
the FDA effectiveness systematic review, the meta-analysis
demonstrating ECT favorability over placebo, and meta-analyses
demonstrating ECT effectiveness being equal to or better than some
antidepressant medications (see FDA Executive Summary from the panel
meeting, Ref. 11).
    While medical/physical risks may occur with ECT, they vary in
frequency, with the most severe risks being quite rare. Death
associated with ECT appears to occur at a very low rate comparable to
that of minor surgical procedures. Recent estimates of the mortality
rate associated with ECT treatment are 1 per 10,000 patients or 1 per
80,000 treatments (Refs. 1, 10).
    The risks of greatest concern to clinicians and patients remain
cognitive and memory impairment. Both the FDA review of literature and
the meta-analyses of the randomized controlled studies indicate that
while post-procedure disorientation occurs frequently, it is transient,
typically resolving within minutes after the procedure is complete. The
systematic meta-analyses of the randomized controlled clinical trials
data by FDA revealed that there is no evidence that disorientation
following ECT is long-term or persistent. The primary areas of concern
for persistent changes are anterograde and retrograde autobiographical
memory. While rates of occurrence are difficult to estimate, it appears
that both types of memory impairment are not uncommon. The literature
review suggests that anterograde memory declines immediately post-ECT
and then returns to baseline within 3 months post-ECT. Retrograde
autobiographical memory declines immediately post-ECT and then appears
to improve over time. It is important to note that while improvement is
seen, impairment may persist past 6 months post-ECT. Data on persistent
retrograde autobiographical memory deficits beyond 6 months is lacking
in the scientific literature. Therefore, it cannot be concluded that
retrograde autobiographical memory returns to baseline over time. (See
tables 6 and 7 and Figures 2-24 from FDA's Executive Summary, Ref. 11.)
    Despite the occurrence and uncertainty of duration of memory
impairment, FDA believes that the potential benefits of ECT outweigh
the risks in patients 18 years of age or older for MDE associated with
MDD or BPD in patients who are treatment-resistant or who require a
rapid response due to the severity of their psychiatric or medical
condition.

VIII. Proposed Special Controls

    FDA believes that special controls, in addition to the general
controls, are necessary to provide a reasonable assurance of safety and
effectiveness for ECT devices indicated for severe MDE associated with
MDD and BPD in patients 18 years of age and older who are treatment-
resistant or who require a rapid response due to the severity of their
psychiatric or medical condition. FDA believes that the risks to health
identified in section V associated with ECT devices indicated for
severe MDE associated with MDD and BPD in patients 18 years of age and
older who are treatment-resistant or who require a rapid response due
to the severity of their psychiatric or medical condition can be
mitigated with general and special controls.
    Several of the risks associated with ECT, including adverse
reaction to anesthetic agents/neuromuscular blocking agents,
cardiovascular complications, death, and pulmonary complications, are
medical/physical risks related to the procedure involving use of the
device. For these risks, safe use of the device is based on appropriate
directions for use. FDA believes that labeling provisions are adequate
to mitigate these risks, including:
     Disclosure of contraindications, precautions, warnings,
and potential adverse effects/complications in both physician and
patient labeling so that users and patients can be advised of
conditions under which ECT treatment should not proceed, and
     Specific device use instructions including information
regarding conduct of pre-ECT patient assessments; and information on
appropriate patient monitoring during an ECT procedure) to minimize
potential ECT procedural complications.
    Other ECT risks are specific to the medical/physical effects of the
induced seizure and potentially severe muscle contractions that result
from use of the device (dental/oral trauma, physical trauma, prolonged
or tardive seizures, pain/discomfort). FDA believes that appropriate
labeling provisions are adequate to mitigate these risks, including:
     Disclosure of contraindications, precautions, warnings,
and adverse effects/complications in both physician and patient
labeling so that users and patients can be advised of conditions under
which ECT treatment should not proceed and are aware of potential
adverse effects associated with ECT treatment, and
     Specific device use instructions including information
regarding conduct of pre-ECT assessments, use of mouth protection
during the procedure, use of general anesthetic agents and
neuromuscular blocking agents, and information on appropriate patient
monitoring during the procedure to minimize potential post-ECT
complications.
    The risks of skin burns can be mitigated by performance testing of
the device to demonstrate safe electrical performance, adhesive
integrity, and physical and chemical stability of the

stimulation electrodes. This risk is further mitigated by providing
specific user instructions regarding proper electrode placement,
including instructions for adequate skin preparation and use of
conductivity gel in placing the electrodes.
    The risk of cognitive and memory impairment can be mitigated by
establishing the technical parameters for the device along with non-
clinical testing data to confirm the electrical characteristics of the
output waveform to ensure that the device performance characteristics
are consistent with existing clinical performance data that supports a
reasonable assurance of safety and effectiveness (see information on
review of clinical performance data in section VII). This risk is
further mitigated by providing information to both the user and patient
on the potential adverse effects of the device, alternative treatments,
and a prominent warning that ECT device use may be associated with:
Disorientation, confusion, and memory problems and limited in its long-
term effectiveness (greater than 3 months). These risks can also be
mitigated by providing instructions to the user that include
recommendations on cognitive status monitoring prior to beginning ECT
and during the course of treatment. Providing this information helps
patients and providers to make informed choices about how and when to
use ECT to maximize benefits and minimize potential adverse effects.
    The risks associated with malfunction of the device can be
mitigated by data demonstrating electrical and mechanical safety and
the functioning of all safety features built into the device (including
the static and dynamic impedance monitoring system); appropriate
analysis/testing of electromagnetic compatibility such that
electromagnetic interference does not cause device malfunction; and
appropriate software verification, validation, and hazard analysis to
ensure that any device software has been adequately designed.
    The potential for manic symptoms or worsening of the condition
being treated can be mitigated by labeling provisions, including:
     The clinical training needed by users of the device to
ensure appropriate use of ECT and appropriate ongoing medical
management of the patient, and
     Information on the patient population in which the device
is intended to be used, including a detailed summary of the clinical
testing pertinent to use of the device, information on the potential
adverse effects of treatment, and information on the typical course of
treatment such that users and patients can make informed decisions
regarding the appropriate use of ECT.
    The risks of adverse skin reactions can be mitigated with
biocompatibility testing to ensure that the materials used in patient-
contacting components of the device are safe for skin contact as well
as labeling that provides information on validated methods for
reprocessing any reusable components between uses.
    Specifically, FDA believes that special controls in Sec.
882.5940(b)(1), together with general controls, are sufficient to
mitigate the risks to health described in section V:
    Table 1 shows how FDA believes that the risks to health identified
in section V can be mitigated by the proposed special controls.

          Table 1--Health Risks and Mitigation Measures for ECT
------------------------------------------------------------------------
            Identified risk                      Special controls
------------------------------------------------------------------------
Adverse reaction to anesthetic agents/   Labeling.
 neuromuscular blocking agents.
Adverse skin reactions.................  Biocompatibility
                                         Labeling.
Cardiovascular complications...........  Labeling.
Cognitive and memory impairment........  Technical parameters
                                         Non-clinical test data.
                                         Labeling.
Death..................................  Labeling.
Dental/oral trauma.....................  Labeling.
Device malfunction.....................  Performance data.
                                         Electromagnetic compatibility.
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Manic symptoms.........................  Labeling.
Pain/discomfort........................  Labeling.
Physical trauma........................  Labeling.
Prolonged or tardive seizures..........  Labeling.
Pulmonary complications................  Labeling.
Skin burns.............................  Performance data.
                                         Labeling.
Worsening of psychiatric symptoms......  Labeling.
------------------------------------------------------------------------

    In addition, FDA is proposing to limit this reclassification to
prescription use devices under 21 CFR 801.109. Under 21 CFR 807.81, the
device would continue to be subject to 510(k) notification
requirements. Elsewhere in this issue of the Federal Register, FDA is
announcing the availability of a draft guidance document entitled
``Electroconvulsive Therapy (ECT) Devices for Class II Intended Uses,''
that, when finalized, would provide recommendations on how to comply
with the special controls proposed in this order, if FDA reclassifies
this device.

IX. Dates New Requirements Apply

    In accordance with section 515(b) of the FD&C Act, FDA is proposing
to require that a PMA be filed with the Agency within 90 days after
issuance of any final order based on this proposal for ECT devices
intended for Certain Specified Intended Uses. 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. 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.''
    FDA intends that under Sec.  812.2(d), the preamble to any final
order based on this proposal will state that, as of the date on which
the filing of a PMA or a notice of completion of a PDP is required to
be filed, the exemptions 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 any device that is: (1) Not legally on the market on
or before that date or (2) legally on the market on or before that date
but for which a PMA or notice of completion of a PDP is not filed by
that date, or for which PMA approval has been denied or withdrawn.
    If a PMA for a class III device is not filed with FDA within 90
days after the date of issuance of any final order requiring premarket
approval for the device, the device would be deemed adulterated under
section 501(f) of the FD&C Act (21 U.S.C. 351(f)). 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 the end of the 90-day period
after the issuance of the final order to avoid interrupting
investigations.
    FDA proposes that following the effective date of any final order,
ECT devices intended for use in treating severe MDE associated with MDD
and BPD in patients 18 years of age and older who are treatment-
resistant or who require a rapid response due to the severity of their
psychiatric or medical condition must comply with the special controls.
FDA notes that a firm whose ECT 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 use in treating severe MDE
associated with MDD and BPD in patients 18 years of age and older who
are treatment-resistant or who require a rapid response due to the
severity of their psychiatric or medical condition, may remove such
intended uses from the device's labeling. FDA proposes that such ECT
devices must comply with the special controls, and, as part of the
special controls, anyone who wishes to continue to market an ECT device
for these uses must submit an amendment to their previously cleared
premarket notification (510(k)) that demonstrates compliance with the
special controls within 60 days after the effective date of the final
order. 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 an ECT device is in compliance with the special controls. If a
510(k) amendment is not submitted within 60 days after the effective
date or if FDA determines that the amendment does not demonstrate
compliance with the special controls, the device may be considered
adulterated under section 501(f)(1)(B) of the FD&C

X. Proposed Findings With Respect to Risks and Benefits

    As required by section 515(b) of the FD&C Act, FDA is publishing
its proposed findings regarding: (1) The degree of risk of illness or
injury designed to be eliminated or reduced by requiring that this
device have an approved PMA or a declared completed PDP when intended
for use in treating any condition other than MDE associated with MDD or
BPD in patients 18 years of age and older who are treatment-resistant
or who require a rapid response due to the severity of their
psychiatric or medical condition and (2) the benefits to the public
from the use of ECT devices for other specified intended uses.
    These findings are based on the reports and recommendations of the
advisory committees (panels) for the classification of these devices
along with information submitted in response to the 515(i) Order (74 FR
16214), the public docket (74 FR 46607) and any additional information
that FDA has obtained. Additional information regarding the risks as
well as classification associated with this device type can be found in
43 FR 55729, 44 FR 51776, 48 FR 14758, and 55 FR 36578.

XI. Device Subject to the Proposal To Require a PMA--ECT Devices for
Certain Specified Intended Uses (Sec.  882.5940(c))

A. Identification

    An electroconvulsive therapy device is a device used for treating
severe psychiatric disturbances by inducing in the patient a major
motor seizure by applying a brief intense electrical current to the
patient's head.

B. Summary of Data

    For intended uses other than the treatment of MDE associated with
MDD or BPD in patients 18 years of age and older who are treatment-
resistant or who require a rapid response due to the severity of their
psychiatric or medical condition, FDA concludes that the safety and
effectiveness of ECT devices have not been established by adequate
scientific evidence. Given the FDA analysis and the advisory panel
deliberations (see http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/ucm240924.htm), there is insufficient evidence of effectiveness for
indications including: schizophrenia, bipolar mania (and mixed states),
schizoaffective disorder, schizophreniform disorder, and catatonia. The
panel recommended Class III designation for schizophrenia, bipolar
mania (and mixed states), schizoaffective disorder, and
schizophreniform disorder; however, the panel did not reach consensus
on the classification of ECT in treatment of catatonia and a review of
the literature for use of ECT in catatonia yielded only one randomized
control trial (Ref. 11). The body of evidence is not sufficiently
robust for FDA to determine that there is a reasonable assurance of
safety and effectiveness for ECT treatment of catatonia. Catatonia is a
potentially life-threatening condition for patients unresponsive to the
current standard of care treatment. FDA encourages collection of
additional data that may support future reclassification of ECT for
this use.
    FDA believes that insufficient information exists regarding the
risks and benefits of the device in order for FDA to determine that
general and/or special controls will provide reasonable assurance of
the safety and effectiveness of ECT for Certain Specified Intended
Uses. As established in section 513(a)(1)(C) of the FD&C Act and 21 CFR
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 in section V
for the use of ECT devices for Certain Specified

Intended Uses, in the absence of an established positive benefit-risk
profile, presents a potential unreasonable risk of illness or injury.

C. Risks to Health

    The risks to health for ECT devices for intended uses other than
the treatment of MDE associated with MDD or BPD in patients 18 years of
age and older who are treatment-resistant or who require a rapid
response due to the severity of their psychiatric or medical condition
are the same as outlined in section V.

D. Benefits of ECT Devices

    As discussed previously, there is limited scientific evidence
regarding the effectiveness of ECT devices for intended uses other than
the treatment of MDE associated with MDD or BPD in patients 18 years of
age and older who are treatment-resistant or who require a rapid
response due to the severity of their psychiatric or medical condition.
Because the benefits of these devices for such uses are unknown, it is
impossible to estimate the direct effect of the devices on patient
outcomes. However, based on claims made about the devices, the devices
have the potential to benefit the public by providing additional
treatment options for schizophrenia, bipolar manic states,
schizoaffective disorder, schizophreniform disorder, and catatonia.

XII. PMA Requirements

    A PMA for ECT devices Certain Specified Intended Uses must include
the information required by section 515(c)(1) of the FD&C Act. Such a
PMA should also include a detailed discussion of the risks identified
previously, as well as a discussion of the effectiveness of the device
for which premarket approval is sought. In addition, a PMA must include
all data and information on: (1) Any risks known, or that should be
reasonably known, to the applicant that have not been identified in
this document; (2) the effectiveness of the device that is the subject
of the application; and (3) full reports of all preclinical and
clinical information from investigations on the safety and
effectiveness of the device for which premarket approval is sought.
    A PMA must include valid scientific evidence to demonstrate
reasonable assurance of the safety and effectiveness of the device for
its intended use (see Sec.  860.7(c)(1)). Valid scientific evidence is
evidence from well-controlled investigations, partially controlled
studies, studies and objective trials without matched controls, well-
documented case histories conducted by qualified experts, and reports
of significant human experience with a marketed device, from which it
can fairly and responsibly be concluded by qualified experts that there
is reasonable assurance of the safety and effectiveness of a device
under its conditions of use. Isolated case reports, random experience,
reports lacking sufficient details to permit scientific evaluation, and
unsubstantiated opinions are not regarded as valid scientific evidence
to show safety or effectiveness. (Sec.  860.7(c)(2)).

XIII. Opportunity To Request a Change in Classification

    Before requiring the filing of a PMA or notice of completion of a
PDP for a device, FDA is required by section 515(b)(2)(D) of the FD&C
Act to provide an opportunity for interested persons to request a
change in the classification of the device based on new information
relevant to the classification. Any proceeding to reclassify the device
will be under the authority of section 513(e) of the FD&C Act.
    A request for a change in the classification of ECT devices is to
be in the form of a reclassification petition containing the
information required by 21 CFR 860.123, including new information
relevant to the classification of the device.

XIV. Codification of Orders

    Prior to the amendments by FDASIA, section 513(e) of the FD&C Act
provided for FDA to issue regulations to reclassify devices and section
515(b) of the FD&C Act provided for FDA to issue regulations to require
approval of an application for premarket approval for preamendments
devices or devices found to be substantially equivalent to
preamendments devices. Because sections 513(e) and 515(b) of the FD&C
Act as amended require FDA to issue final orders rather than
regulations, 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 (CFR). Therefore, under section 513(e)(1)(A)(i) of the FD&C
Act, as amended by FDASIA, in this proposed order, we are proposing to
codify the reclassification of ECT devices for use in treating severe
Major Depressive Episode (MDE) associated with Major Depressive
Disorder (MDD) or Bipolar Disorder (BPD) in patients 18 years of age
and older who are treatment-resistant or who require a rapid response
due to the severity of their psychiatric or medical condition into
class II by amending Sec.  882.5940.

XV. Environmental Impact

    The Agency has determined under 21 CFR 25.30(h) 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.

XVI. Paperwork Reduction Act of 1995

    This proposed 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.
3501-3520). The collections of information in 21 CFR part 807, subpart
E, have been approved under OMB control number 0910-0120. The
collections of information in 21 CFR part 812 have been approved under
OMB control number 0910-0078. The collections of information in 21 CFR
part 814 have been approved under OMB control number 0910-0231.
    The device and patient warning labeling provisions in this proposed
rule are not subject to review by OMB because they do not constitute a
``collection of information'' under the PRA. Rather, the recommended
labeling is a ``public disclosure of information originally supplied by
the Federal government to the recipient for the purpose of disclosure
to the public'' (5 CFR 1320.3(c)(2)).

XVII. Proposed Effective Date

    FDA is proposing that any final order based on this proposal become
effective 90 days after the date of publication in the Federal
Register.

XVIII. Specific Questions for Comment

    Interested persons may submit either electronic comments regarding
this document to http://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES). FDA is explicitly
seeking comments on whether: (1) The term ``treatment resistant'' and
the phrase ``require rapid response'' provide sufficient clarity to the
population for which ECT benefits outweigh risks and (2) if 60 days is
an appropriate time to allow existing manufacturers who do not intend
to market their ECT device(s) for uses other than use in treating
severe MDE associated with MDD and BPD in patients 18 years of age and
older who are treatment-resistant or who require a rapid response due
to the severity of their psychiatric or medical condition to prepare
and submit 510(k) amendments for ECT devices.

XIX. References

    The following references are on display in the Division of Dockets
Management (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also
available electronically at http://www.regulations.gov. FDA has
verified the Web site addresses, as of the date this document publishes
in the Federal Register, but Web sites are subject to change over time.

    1. American Psychiatric Association. 2001. The Practice of
Electroconvulsive Therapy: Recommendations for Treatment, Training
and Privileging--A Task Force Report, 2nd ed. American Psychiatric
Press, Washington, DC.
    2. Royal College of Psychiatrists. The ECT Handbook. Ed. A.I.F.
Scott. The Third Report of the Royal College of Psychiatrists'
Special Committee on ECT. 2004. Available at: http://www.ectron.co.uk/ws-public/uploads/143_cr128.pdf
    3. NICE (National Institute for Health and Clinical Excellence).
Guidance on the Use of Electroconvulsive Therapy. Technology
Appraisal Guidance: 59:1-37, 2003. Available at: https://www.nice.org.uk/guidance/ta59
    4. NICE (National Institute for Health and Clinical Excellence).
Depression in Adults (update). National Clinical Practice Guideline:
90:1-585, 2009. Available at: https://www.nice.org.uk/guidance/cg90
    5. U.S. Department of Health and Human Services. Mental Health:
A Report of the Surgeon General. Rockville, MD: Substance Abuse and
Mental Health Services Administration/Center for Mental Health
Services; National Institutes of Health/National Institute of Mental
Health, 1999. Available at: http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/NNBBHS
    6. Semkovska, M., D.M. McLoughlin, ``Objective Cognitive
Performance Associated with Electroconvulsive Therapy for
Depression: A Systematic Review and Meta-Analysis.'' Biological
Psychiatry: 68:568-577, 2010.
    7. Greenhalgh, J., C. Knight, D. Hind, C. Beverley, S. Walters,
``Clinical and Cost-effectiveness of Electroconvulsive Therapy for
Depressive Illness, Schizophrenia, Catatonia and Mania: Systematic
Reviews and Economic Modelling Studies. Health Technology
Assessment: 9(9):1-170, 2005. J.C. Fournier, R.J. DeRubeis, S.D.
Hollon, S. Dimidjian, J.D. Amsterdam, R.C. Shelton, J. Fawcett,
``Antidepressant Drug Effects and Depression Severity.'' Journal of
the American Medical Association: 303(1):47-53, 2010.
    8. Kirsch, I., B.J. Deacon, T.B. Huedo-Medina, A. Scoboria, T.J.
Moore, B.T. Johnson, ``Initial Severity and Antidepressant Benefits:
A Meta-analysis of Data Submitted to the Food and Drug
Administration.'' PLoS Medicine: 5(2):260-268, 2008.
    9. Watts, B.V., et al. ``An Examination of Mortality and Other
Adverse Events Related to Electroconvulsive Therapy Using a National
Adverse Event Report System.'' Journal of ECT, 2010.
    10. Girish, K., N.S. Gill, ``Electroconvulsive Therapy in
Lorazepam Non-Responsive Catatonia.'' Indian Journal of Psychiatry:
45(1):21-25, 2003.
    11. FDA Executive Summary, Prepared for the January 27-28, 2011
meeting of the Neurological Devices Panel, Meeting to Discuss the
Classification of Electroconvulsive Therapy Devices (ECT), available
at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/ucm240924.htm.

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, it is
proposed that 21 CFR part 882 be amended as follows:

PART 882--NEUROLOGICAL DEVICES

0
1. The authority citation for 21 CFR part 882 continues to read as
follows:

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

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2. Revise Sec.  882.5940 to read as follows:

Sec.  882.5940  Electroconvulsive therapy device.

    (a) Identification. An electroconvulsive therapy device is a
prescription device, including the pulse generator and its stimulation
electrodes and accessories, used for treating severe psychiatric
disturbances by inducing in the patient a major motor seizure by
applying a brief intense electrical current to the patient's head.
    (b) Classification. (1) Class II (special controls) when the device
is intended to treat severe major depressive episodes (associated with
major depressive disorder or bipolar disorder) in patients 18 years of
age and older who are treatment-resistant or who require a rapid
response due to the severity of their psychiatric or medical condition.
The special controls for this device are:
    (i) The technical parameters of the device, including waveform,
output mode, pulse duration, frequency, train delivery, maximum charge
and energy, and the type of impedance monitoring system must be fully
characterized.
    (ii) Non-clinical testing data must confirm the electrical
characteristics of the output waveform.
    (iii) Components (and accessories) of the device that come into
human contact must be demonstrated to be biocompatible.
    (iv) Performance data must demonstrate electrical and mechanical
safety and the functioning of all safety features built into the device
including the static and dynamic impedance monitoring system.
    (v) Appropriate analysis/testing must validate electromagnetic
compatibility.
    (vi) Appropriate software verification, validation, and hazard
analysis must be performed.
    (vii) Performance data must demonstrate electrical performance,
adhesive integrity, and physical and chemical stability of the
stimulation electrodes.
    (viii) The labeling for the device must include the following:
    (A) Information related to generic adverse events associated with
ECT treatment.
    (B) Instructions must contain the following specific
recommendations to the user of the device:
    (1) Conduct of pre-ECT medical and psychiatric assessment
(including pertinent medical and psychiatric history, physical
examination, anesthesia assessment, dental assessment, and other
studies as clinically appropriate);
    (2) Use of patient monitoring during the procedure;
    (3) Use of general anesthesia and neuromuscular blocking agents;
    (4) Use of mouth/dental protection during the procedure;
    (5) Use of EEG monitoring until seizure termination;
    (6) Instructions on electrode placement, including adequate skin
preparation and use of conductivity gel; and
    (7) Cognitive status monitoring prior to beginning ECT and during
the course of treatment via formal neuropsychological assessment for
evaluating specific cognitive functions (e.g., orientation, attention,
memory, executive function).
    (C) Clinical training needed by users of the device.
    (D) Information on the patient population in which the device is
intended to be used.
    (E) Information on how the device operates and the typical course
of treatment.
    (F) 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.
    (G) A detailed summary of the device technical parameters;
    (H) Where appropriate, validated methods and instructions for
reprocessing of any reusable components.
    (I) The following statement, prominently placed: ``Warning: ECT

device use may be associated with: disorientation, confusion, and
memory problems.''
    (J) Absent performance data demonstrating a beneficial effect of
longer term use, generally considered treatment in excess of 3 months,
the following statement, prominently placed: ``Warning: When used as
intended this device provides short-term relief of symptoms. The long-
term safety and effectiveness of ECT treatment has not been
demonstrated.''
    (ix) Patient labeling must be provided and include:
    (A) Relevant contraindications, warnings, precautions.
    (B) A summation 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.
    (C) Information on how the device operates and the typical course
of treatment.
    (D) The potential benefits.
    (E) Alternative treatments.
    (F) The following statement, prominently placed: ``Warning: ECT
device use may be associated with: disorientation, confusion, and
memory problems.''
    (G) Absent performance data demonstrating a beneficial effect of
longer term use, generally considered treatment in excess of 3 months,
the following statement, prominently placed: ``Warning: When used as
intended this device provides short-term relief of symptoms. The long-
term safety and effectiveness of ECT treatment has not been
demonstrated.''
    (H) The following statements on known risks of ECT, absent
performance data demonstrating that these risks do not apply:
    (1) ECT treatment may be associated with disorientation, confusion
and memory loss, including short-term (anterograde) and long-term
(autobiographical) memory loss following treatment. These side effects
tend to go away within a few days to a few months after the last
treatment with ECT. However, some patients have reported a permanent
loss of memories of personal life events (i.e., autobiographical
memory). Improvements in the way ECT is applied to patients currently,
with controlled electric currents and electrode placement, can minimize
but not completely eliminate, these risks.
    (2) Patients treated with ECT may also experience manic symptoms
(including euphoria and/or irritability, impulsivity, racing thoughts,
distractibility, grandiosity, increased activity, talkativeness, and
decreased need for sleep) or a worsening of the psychiatric symptoms
they are being treated for.
    (3) The physical risks of ECT may include the following (in order
of frequency of occurrence):
    (i) Pain/somatic discomfort (including headache, muscle soreness,
and nausea).
    (ii) Skin burns.
    (iii) Physical trauma (including fractures, contusions, injury from
falls, dental and oral injury).
    (iv) Prolonged or delayed onset seizures.
    (v) Pulmonary complications (insufficient, or lack of breathing, or
inhalation of foreign substance into the lungs).
    (vi) Cardiovascular complications (heart attack, high or low blood
pressure, and stroke).
    (vii) Death.
    (viii) Devices marketed prior to the effective date of this
reclassification must have an amendment submitted to their previously
cleared premarket notification (510(k)) that demonstrates compliance
with these special controls within 60 days after the effective date of
this reclassification.
    (2) Classification: Class III (premarket approval) for the
following intended uses: schizophrenia, bipolar manic states,
schizoaffective disorder, schizophreniform disorder, and catatonia.
    (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 [A DATE WILL BE ADDED 90 DAYS AFTER
DATE OF PUBLICATION OF A FUTURE FINAL ORDER IN THE Federal Register],
for any electroconvulsive therapy 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 [A DATE
WILL BE ADDED 90 DAYS AFTER DATE OF PUBLICATION OF A FUTURE FINAL ORDER
IN THE Federal Register], been found to be substantially equivalent to
any electroconvulsive therapy device with an intended use described in
paragraph (b)(2) of this section, that was in commercial distribution
before May 28, 1976. Any other electroconvulsive therapy 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 18, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-32592 Filed 12-28-15; 8:45 am]
 BILLING CODE 4164-01-P