80 FR 81223 - 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

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 249 (December 29, 2015)

Page Range		81223-81233
FR Document		2015-32592

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.

Federal Register, Volume 80 Issue 249 (Tuesday, December 29, 2015)

[Federal Register Volume 80, Number 249 (Tuesday, December 29, 2015)]
[Proposed Rules]
[Pages 81223-81233]
From the Federal Register Online [www.thefederalregister.org]
[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

[[Page 81224]]

Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1615, Silver Spring, MD 20993, 301-796-6283,
michael.ryan@fda.hhs.gov.

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.

[[Page 81225]]

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

[[Page 81226]]

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

[[Page 81227]]

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

[[Page 81228]]

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

[[Page 81229]]

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

[[Page 81230]]

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

[[Page 81231]]

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.

[[Page 81232]]

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.

0
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

[[Page 81233]]

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

81224 Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules

Radiological Health, Food and Drug automatically classified by section Section 513(e) of the FD&C Act
Administration, 10903 New Hampshire 513(f) of the FD&C Act into class III governs reclassification of classified
Ave., Bldg. 66, Rm. 1615, Silver Spring, without any FDA rulemaking process. preamendments devices. This section
MD 20993, 301–796–6283, Those devices remain in class III and provides that FDA may, by
michael.ryan@fda.hhs.gov. require premarket approval unless, and administrative order, reclassify a device
SUPPLEMENTARY INFORMATION: until, the device is reclassified into class based upon ‘‘new information.’’ FDA
I or II or FDA issues an order finding the can initiate a reclassification under
I. Background—Regulatory Authorities device to be substantially equivalent, in section 513(e) of the FD&C Act or an
The Federal Food, Drug, and Cosmetic accordance with section 513(i) of the interested person may petition FDA to
Act (the FD&C Act), as amended by the FD&C Act, to a predicate device that reclassify a preamendments device. The
Medical Device Amendments of 1976 does not require premarket approval. term ‘‘new information,’’ as used in
(the 1976 amendments) (Pub. L. 94– The Agency determines whether new section 513(e) of the FD&C Act, includes
295), the Safe Medical Devices Act of devices are substantially equivalent to information developed as a result of a
1990 (SMDA) (Pub. L. 101–629), Food predicate devices by means of reevaluation of the data before the
and Drug Administration Modernization premarket notification procedures in Agency when the device was originally
Act of 1997 (FDAMA) (Pub. L. 105–115), section 510(k) of the FD&C Act (21 classified, as well as information not
the Medical Device User Fee and U.S.C. 360(k)) and part 807 (21 CFR part presented, not available, or not
Modernization Act of 2002 (MDUFMA) 807). developed at that time. (See, e.g.,
(Pub. L. 107–250), the Medical Devices A preamendments device that has Holland Rantos Co. v. United States
Technical Corrections Act (Pub. L. 108– been classified into class III and devices Department of Health, Education, and
214), the Food and Drug Administration found substantially equivalent by means Welfare, 587 F.2d 1173, 1174 n.1 (D.C.
Amendments Act of 2007 (Pub. L. 110– of premarket notification (510(k)) Cir. 1978); Upjohn v. Finch, 422 F.2d
85), and the Food and Drug procedures to such a preamendments 944 (6th Cir. 1970); Bell v. Goddard, 366
Administration Safety and Innovation device or to a device within that type F.2d 177 (7th Cir. 1966).)
Act (FDASIA) (Pub. L. 112–144), may be marketed without submission of Reevaluation of the data previously
establishes a comprehensive system for a PMA until FDA issues a final order before the Agency is an appropriate
the regulation of medical devices under section 515(b) of the FD&C Act basis for subsequent regulatory action
intended for human use. Section 513 of (21 U.S.C. 360e(b)) requiring premarket where the reevaluation is made in light
the FD&C Act (21 U.S.C. 360c) approval or until the device is of newly available regulatory authority
established three categories (classes) of subsequently reclassified into class I or (see Bell, 366 F.2d at 181; Ethicon, Inc.
devices, reflecting the regulatory v. FDA, 762 F. Supp. 382, 388–391
class II.
controls needed to provide reasonable (D.D.C. 1991)) or in light of changes in
Although, under the FD&C Act, the ‘‘medical science’’ (see Upjohn, 422
assurance of their safety and
manufacturer of a class III F.2d at 951). Whether data before the
effectiveness. The three categories of
preamendments device may respond to Agency are old or new data, the ‘‘new
devices are class I (general controls),
the call for PMAs by filing a PMA or a information’’ to support reclassification
class II (special controls), and class III
(premarket approval). One type of notice of completion of a PDP, in under section 513(e) must be ‘‘valid
general control provided by the FD&C practice, the option of filing a notice of scientific evidence,’’ as defined in
Act is a restriction on the sale, completion of a PDP has not been used. section 513(a)(3) of the FD&C Act and
distribution, or use of a device under For simplicity, although corresponding § 860.7(c)(2) (21 CFR 860.7(c)(2)). (See,
section 520(e) of the FD&C Act (21 requirements for PDPs remain available e.g., General Medical Co. v. FDA, 770
U.S.C. 360j(e)). A restriction under to manufacturers in response to a final F.2d 214 (D.C. Cir. 1985); Contact Lens
section 520(e) of the FD&C Act must be order under section 515(b) of the FD&C Mfrs. Assoc. v. FDA, 766 F.2d 592 (D.C.
implemented through rulemaking Act, this document will refer only to the Cir. 1985), cert. denied, 474 U.S. 1062
procedures, unlike the administrative requirement for the filing and receiving (1986).)
order procedures that apply to this approval of a PMA. FDA relies upon ‘‘valid scientific
proposed reclassification under section On July 9, 2012, FDASIA was enacted. evidence’’ in the classification process
513(e) of the FD&C Act, as amended by Section 608(a) of FDASIA (126 Stat. to determine the level of regulation for
FDASIA. 1056) amended section 513(e) of the devices. To be considered in the
Under section 513(d) of the FD&C Act, FD&C Act, changing the process for reclassification process, the ‘‘valid
devices that were in commercial reclassifying a device from rulemaking scientific evidence’’ upon which the
distribution before the enactment of the to an administrative order. Section Agency relies must be publicly
1976 amendments, May 28, 1976 608(b) of FDASIA amended section available. Publicly available information
(generally referred to as preamendments 515(b) of the FD&C Act changing the excludes trade secret and/or
devices), are classified after FDA has: (1) process for requiring premarket confidential commercial information,
Received a recommendation from a approval for a preamendments class III e.g., the contents of a pending PMA.
device classification panel (an FDA device from rulemaking to an (See section 520(c) of the FD&C Act .)
advisory committee); (2) published the administrative order. Section 520(h)(4) of the FD&C Act,
panel’s recommendation for comment, added by FDAMA, provides that FDA
A. Reclassification
along with a proposed regulation may use, for reclassification of a device,
classifying the device; and (3) published FDA is publishing this document to certain information in a PMA 6 years
jstallworth on DSK7TPTVN1PROD with PROPOSALS

a final regulation classifying the device. propose the reclassification of ECT after the application has been approved.
FDA has classified most devices for use in treating severe MDE This includes information from clinical
preamendments devices under these associated with MDD or BPD in patients and preclinical tests or studies that
procedures. 18 years of age and older who are demonstrate the safety or effectiveness
Devices that were not in commercial treatment-resistant or who require a of the device but does not include
distribution prior to May 28, 1976 rapid response due to the severity of descriptions of methods of manufacture
(generally referred to as their psychiatric or medical condition or product composition and other trade
postamendments devices) are from class III to class II. secrets.

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81226 Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules

identified precisely enough such that of the electrodes to the skin, changing and its stimulation electrodes and
special controls could be established anesthetic medications or doses, and accessories.
that would provide reasonable changing concurrent medications.
In 2009, FDA also opened a public IV. Proposed Reclassification
assurance of the safety and effectiveness
of the device. docket to receive information and FDA is proposing that ECT devices
On August 13, 1982, the American comments regarding the current intended for treating severe MDE
Psychiatric Association (APA) classification process for ECT by associated with MDD and BPD in
submitted a reclassification petition to January 8, 2010 (74 FR 46607, patients 18 years of age and older who
FDA requesting that ECT be classified September 10, 2009). FDA received over are treatment-resistant or who require a
into class II. The reclassification 3,000 submissions to the docket, with rapid response due to the severity of
petition was discussed at a Panel the majority of respondents, their psychiatric or medical condition
meeting on November 4, 1982 (47 FR approximately 80 percent, opposing be reclassified from class III to class II.
44611, October 8, 1982). The Panel reclassification of ECT. The majority of In this proposed order, the Agency has
recommended that ECT be reclassified those opposing reclassification of ECT identified special controls under section
from class III to class II. FDA tentatively cited adverse events from ECT treatment 513(a)(1)(B) of the FD&C Act that,
agreed that there was sufficient as the basis for their opposition. The together with general controls
evidence to reclassify to class II for most common type of adverse event applicable to the devices, would
severe depression and schizophrenia mentioned in the public docket were provide reasonable assurance of safety
and published a notice of intent to memory adverse events, followed by and effectiveness. Absent the special
reclassify (48 FR 14758, April 5, 1983). other cognitive complaints, brain controls identified in this proposed
Several comments received by the damage, and death. order, general controls applicable to the
Agency argued that research and data On January 27–28, 2011, a meeting of device are insufficient to provide
did not support that ECT is an effective the Neurological Devices Panel was held reasonable assurance of the safety and
therapy for schizophrenia, and after to discuss the classification of ECT effectiveness of the device.
careful review of the scientific literature devices for treatment of several Therefore, in accordance with
and the APA’s petition, FDA agreed disorders. There was panel consensus sections 513(e) and 515(i) of the FD&C
with the comments. In the subsequent recommending class III for Act and21 CFR 860.130, based on new
proposed rule (55 FR 36578, September Schizophrenia, Bipolar manic states, information with respect to the devices
5, 1990), FDA determined that the Schizoaffective, and Schizophreniform and taking into account the public
evidence of effectiveness for disorder. The Panel did not reach health benefit of the use of the device
schizophrenia was inconclusive, and consensus on the classification of ECT and the nature and known incidence of
proposed that ECT be reclassified to for depression (unipolar and bipolar) the risk of the device, FDA, on its own
class II only for severe depression and and catatonia. The Panel transcript and initiative, is proposing to reclassify this
remain class III for all other indications. other meeting materials are available on preamendments class III device into
In 1995, FDA published an order for the FDA’s Web site (http://www.fda.gov/ class II when the device is intended to
submission of safety and effectiveness AdvisoryCommittees/ treat severe MDE associated with MDD
information on ECT devices (60 FR CommitteesMeetingMaterials/ and BPD in patients 18 years of age and
41986, August 14, 1995). In 2003, FDA MedicalDevices/ older who are treatment-resistant or
published an intent to withdraw the MedicalDevicesAdvisoryCommittee/ who require a rapid response due to the
1990 proposed rule (68 FR 19766, April NeurologicalDevicesPanel/ severity of their psychiatric or medical
22, 2003) followed by withdrawal in ucm240924.htm). condition. FDA believes that this new
2004 (69 FR 68831, November 26, 2004) information is sufficient to demonstrate
III. Device Description that the proposed special controls can
of the proposed rule for reclassification
of ECT, along with other FDA proposed The ECT device consists of an effectively mitigate the risks to health
rules that had been outstanding for more electrical generator and a pair of identified in the next section, and that
than 5 years because the proposals were electrodes that apply a brief intense these special controls, together with
no longer considered viable candidates electrical current to the head in order to general controls, will provide a
for final action. Thus, ECT devices induce a generalized seizure. In reasonable assurance of safety and
remain in class III for all indications. addition to generating and modulating effectiveness for ECT devices intended
In 2009, FDA published an order for the electrical functions of the stimulus, for treating severe MDE associated with
the submission of safety and the box enclosing the generator also has MDD and BPD in patients 18 years of
effectiveness information on ECT capabilities and displays for age and older who are treatment-
devices by August 7, 2009 (74 FR 16214, physiological monitoring. The device resistant or who require a rapid
April 9, 2009). In response to that order, parameters such as voltage, pulse width, response due to the severity of their
FDA received two submissions from frequency, and treatment (train) psychiatric or medical condition.
ECT manufacturers suggesting that ECT duration are adjustable. The typical Section 510(m) of the FD&C Act
devices could be reclassified to class II. display may provide information such authorizes the Agency to exempt class II
The manufacturers stated that safety and as Electroencephalograph (EEG) activity, devices from premarket notification
effectiveness of these devices may be stimulus administration, total charge, (510(k)) submission. FDA has
assured by reducing the frequency of energy, and impedance. These devices considered ECT devices intended for
treatments, temporary or permanent are currently regulated under § 882.5940 treating severe MDE associated with
jstallworth on DSK7TPTVN1PROD with PROPOSALS

interruption of treatments, reduction of (21 CFR 882.5940), product code GXC. MDD and BPD in patients 18 years of
stimulus dose, electrode placement, FDA is proposing in this order to age and older who are treatment-
dosage or type of anesthetic (or other) modify the identification language from resistant or who require a rapid
medications, including minimizing how it is presently written in response due to the severity of their
psychotropic medications, brief pulse or § 882.5940(a). FDA is clarifying in the psychiatric or medical condition and
ultra-brief pulse waveform stimulus, identification that these are prescription decided that the device does require
EEG monitoring, proper preparation devices and clarifying that this device premarket notification. Therefore, the
(including conductive gel) and contact type includes the ECT pulse generator Agency does not intend to exempt this

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Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules 81227

proposed class II device from premarket • Prolonged or tardive seizures. ECT reclassification of ECT to class II with
notification (510(k)) submission. treatment may result in prolonged or special controls for severe MDE
delayed seizures, and status epilepticus associated with MDD and BPD in
V. Risks to Health
(continuous unremittent seizure) may patients 18 years of age and older who
After considering the available ensue if prolonged seizures are not are treatment-resistant or who require a
information from the reports and properly treated. rapid response due to the severity of
recommendations of the advisory • Pulmonary complications. ECT their psychiatric or medical condition.
committees (panels) for the treatment may result in prolonged apnea FDA’s review of the clinical literature
classification of these devices, FDA has (no breathing) or inhalation of foreign has been previously summarized in the
evaluated the risks to health associated material, such as regurgitated stomach Executive Summary to the January 27–
with the use of ECT devices and contents. 28, 2011, Neurological Device Panel
determined that the following risks to • Skin burns. Excessive electrical meeting to discuss ECT classification
health are associated with its use: current or improperly designed (http://www.fda.gov/downloads/
• Adverse reaction to anesthetic electrodes may cause the patient’s skin AdvisoryCommittees/
agents/neuromuscular blocking agents. under the electrodes to be burned. CommitteesMeetingMaterials/
The muscle relaxing and sedating (or • Worsening of psychiatric symptoms.
MedicalDevices/
sleep inducing) drugs that are a part of ECT treatment may be ineffective and
MedicalDevicesAdvisoryCommittee/
the procedure may hamper the patient’s therefore may result in worsening
psychiatric symptoms. NeurologicalDevicesPanel/
ability to breathe spontaneously. UCM240933.pdf). The largest body of
• Adverse skin reactions. The patient- VI. Summary of Reasons for evidence for ECT effectiveness exists for
contacting materials of the device may Reclassification MDE associated with MDD and BPD in
cause an adverse immunological or
FDA believes that ECT devices patients 18 years of age and older. Based
allergic reaction in a patient.
• Cardiovascular complications. The indicated for severe MDE associated on this review, FDA concluded that ECT
therapeutic convulsions may be with MDD and BPD in patients 18 years demonstrated effectiveness in the acute
accompanied by arrhythmias (irregular of age and older who are treatment- phase (less than 3 months after
heartbeat) or ischemia/infarction (i.e., resistant or who require a rapid treatment); however, the Panel members
heart attack). Hypertension (high blood response due to the severity of their had various scientific opinions
pressure) as well as hypotension (low psychiatric or medical condition should regarding the long-term effectiveness of
blood pressure) may be associated with be reclassified from class III to class II ECT for the treatment of depression, but
ECT treatment. ECT treatment may also because, in light of new information agreed that it was effective in the acute
result in stroke (impairment of blood about the effectiveness of these devices, phase. Panel members indicated that
flow to the brain or bleeding in the special controls, in addition to general controlled clinical trials are lacking
brain). controls, can be established to provide regarding the effectiveness of ECT
• Cognition and memory impairment. reasonable assurance of safety and beyond the acute phase, in part, due to
ECT treatment may result in memory effectiveness of the device, and because the fact that many patients have an
impairment, specifically immediate general controls themselves are initial improvement in the depressive
post-treatment disorientation, insufficient to provide reasonable symptoms following an acute course of
anterograde memory impairment and assurance of its safety and effectiveness. ECT and are able to return to alternative
retrograde personal (autobiographical) FDA believes that in the specified treatments for managing depression
memory impairment. patient population, and with the such as medications and psychotherapy.
• Death. Death may result from application of general and special The findings from FDA’s review are
various complications of ECT such as controls as described in this document, consistent with other recently
reactions to anesthesia, cardiovascular the probable benefit to health from use conducted, comprehensive, high quality
complications, pulmonary of the device outweighs the probable systematic reviews, including the
complications, or stroke. injury or illness from such use. FDA American Psychiatric Association (APA)
• Dental/oral trauma. Dental acknowledges significant risks recommendations/guidelines (Ref. 1),
fractures, dislocations, lacerations, and associated with ECT but believes that the Third report of the Royal College of
prosthetic damage may occur as a result for the specified population—patients Psychiatrists’ Special Committee on
of strong muscle contractions during age 18 years of age and older ECT (2004) (Ref. 2), the United Kingdom
treatment. experiencing a severe MDE associated National Institute for Health and
• Device malfunction. Faulty with MDD or BPD for whom other Clinical Excellence (NICE 2003; NICE
hardware, software or accessories treatment options have not been 2009) (Refs. 3, 4), the Surgeon General’s
(electrodes) or improper use may cause successful or for whom rapid, definitive report on mental health (Ref. 5),
electrical hazards, such as the risk of response is needed due the severity of systematic reviews by Semkovska and
excessive dose administration, a psychiatric or medical condition—the McLoughlin (Ref. 6), and Greenhalgh et
prolonged seizures, and skin burns. probable benefit of ECT outweighs these al (Ref. 7). These findings from the FDA
• Manic symptoms. ECT treatment risks. FDA is inviting comments on review included examining the results
may result in the development of whether the term ‘‘treatment resistant’’ of over 60 randomized controlled
hypomanic or manic symptoms. and the phrase ‘‘require rapid response’’ clinical trials comparing ECT with
• Pain/discomfort. The patient may provide sufficient clarity to the either placebo (sham) or antidepressant
jstallworth on DSK7TPTVN1PROD with PROPOSALS

experience mild to moderate pain population for which ECT benefits therapy in which ECT was superior for
following the motor seizure induced by outweigh risks. patients with MDD and BPD in patients
ECT treatment. 18 years of age and older who are
• Physical trauma. Inadequate VII. Summary of Data Upon Which the treatment-resistant or who require a
supportive drug treatment may allow Reclassification Is Based rapid response due to the severity of
the patient to be injured from Since the time of the original ECT their psychiatric or medical condition.
unconscious violent movements during device classification, sufficient evidence In addition, FDA conducted a
convulsions. has been developed to support a systematic meta-analysis of these

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81228 Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules

studies which supported a robust effect to occur at a very low rate comparable ECT devices indicated for severe MDE
of ECT in the short-term (e.g. 3 months) to that of minor surgical procedures. associated with MDD and BPD in
(Ref. 11). Recent estimates of the mortality rate patients 18 years of age and older who
FDA also examined other conditions, associated with ECT treatment are 1 per are treatment-resistant or who require a
including bipolar mania, schizophrenia, 10,000 patients or 1 per 80,000 rapid response due to the severity of
schizoaffective disorder, treatments (Refs. 1, 10). their psychiatric or medical condition
schizophreniform disorder, and The risks of greatest concern to can be mitigated with general and
catatonia, but there were insufficient clinicians and patients remain cognitive special controls.
clinical data to support effectiveness for and memory impairment. Both the FDA Several of the risks associated with
these conditions. FDA relied upon review of literature and the meta- ECT, including adverse reaction to
literature describing clinical study data analyses of the randomized controlled anesthetic agents/neuromuscular
collected largely in patients age 18 and studies indicate that while post- blocking agents, cardiovascular
older. Data on the use of ECT in procedure disorientation occurs complications, death, and pulmonary
children and adolescents is limited and frequently, it is transient, typically complications, are medical/physical
hence the recommended reclassification resolving within minutes after the risks related to the procedure involving
is limited to patients 18 years of age and procedure is complete. The systematic use of the device. For these risks, safe
older. Most of the published literature meta-analyses of the randomized use of the device is based on
FDA is aware of and reviewed focused controlled clinical trials data by FDA appropriate directions for use. FDA
on subject populations that did not revealed that there is no evidence that believes that labeling provisions are
receive benefit from prior treatments; disorientation following ECT is long- adequate to mitigate these risks,
therefore, the recommended term or persistent. The primary areas of including:
reclassification is limited to treatment concern for persistent changes are • Disclosure of contraindications,
resistant populations as well as those anterograde and retrograde precautions, warnings, and potential
patients who require a rapid response autobiographical memory. While rates adverse effects/complications in both
due to the severity of their psychiatric of occurrence are difficult to estimate, it physician and patient labeling so that
or medical condition. Further, practice appears that both types of memory users and patients can be advised of
guidelines published by the APA task impairment are not uncommon. The conditions under which ECT treatment
force on ECT and the NICE in the literature review suggests that should not proceed, and
United Kingdom recommend that ECT anterograde memory declines • Specific device use instructions
be considered for primary use (i.e., prior immediately post-ECT and then returns including information regarding
to medications) when there is a need for to baseline within 3 months post-ECT. conduct of pre-ECT patient assessments;
rapid, definitive response due to the Retrograde autobiographical memory and information on appropriate patient
severity of a psychiatric or medical declines immediately post-ECT and monitoring during an ECT procedure) to
condition. Conventional treatments then appears to improve over time. It is minimize potential ECT procedural
such as medications and psychotherapy important to note that while complications.
are likely to be less effective for a rapid improvement is seen, impairment may Other ECT risks are specific to the
definitive response, thus the persist past 6 months post-ECT. Data on medical/physical effects of the induced
recommended reclassification for ECT persistent retrograde autobiographical seizure and potentially severe muscle
includes patients who require a rapid memory deficits beyond 6 months is contractions that result from use of the
response because of the severity of their lacking in the scientific literature. device (dental/oral trauma, physical
psychiatric or medical condition. Therefore, it cannot be concluded that trauma, prolonged or tardive seizures,
Panel deliberations focused heavily retrograde autobiographical memory pain/discomfort). FDA believes that
on ECT versus sham meta-analysis for returns to baseline over time. (See tables appropriate labeling provisions are
treatment of depression. Discussion 6 and 7 and Figures 2–24 from FDA’s adequate to mitigate these risks,
focused on the clinical meaningfulness Executive Summary, Ref. 11.) including:
of the effect size, the wide confidence Despite the occurrence and • Disclosure of contraindications,
interval which included 0 (i.e., the uncertainty of duration of memory precautions, warnings, and adverse
possibility of no effect), and the sources impairment, FDA believes that the effects/complications in both physician
of variability in the dataset. Compared potential benefits of ECT outweigh the and patient labeling so that users and
with other approved treatments for risks in patients 18 years of age or older patients can be advised of conditions
depression, the data suggest that the for MDE associated with MDD or BPD under which ECT treatment should not
effect size of ECT is at least as large as, in patients who are treatment-resistant proceed and are aware of potential
or larger than, that of other treatments or who require a rapid response due to adverse effects associated with ECT
(i.e., antidepressant medications) (Refs. the severity of their psychiatric or treatment, and
8, 9). In addition, other sources of medical condition. • Specific device use instructions
evidence supported the effectiveness including information regarding
claim of ECT, including the FDA VIII. Proposed Special Controls conduct of pre-ECT assessments, use of
effectiveness systematic review, the FDA believes that special controls, in mouth protection during the procedure,
meta-analysis demonstrating ECT addition to the general controls, are use of general anesthetic agents and
favorability over placebo, and meta- necessary to provide a reasonable neuromuscular blocking agents, and
analyses demonstrating ECT assurance of safety and effectiveness for information on appropriate patient
jstallworth on DSK7TPTVN1PROD with PROPOSALS

effectiveness being equal to or better ECT devices indicated for severe MDE monitoring during the procedure to
than some antidepressant medications associated with MDD and BPD in minimize potential post-ECT
(see FDA Executive Summary from the patients 18 years of age and older who complications.
panel meeting, Ref. 11). are treatment-resistant or who require a The risks of skin burns can be
While medical/physical risks may rapid response due to the severity of mitigated by performance testing of the
occur with ECT, they vary in frequency, their psychiatric or medical condition. device to demonstrate safe electrical
with the most severe risks being quite FDA believes that the risks to health performance, adhesive integrity, and
rare. Death associated with ECT appears identified in section V associated with physical and chemical stability of the

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Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules 81229

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

TABLE 1—HEALTH RISKS AND MITIGATION MEASURES FOR ECT
Identified risk Special controls

Adverse reaction to anesthetic agents/neuromuscular blocking agents .. Labeling.
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 with the special controls proposed in distribution before May 28, 1976, or
this reclassification to prescription use this order, if FDA reclassifies this whose device has been found to be
devices under 21 CFR 801.109. Under device. substantially equivalent to such a
21 CFR 807.81, the device would device, will be permitted to continue
IX. Dates New Requirements Apply
continue to be subject to 510(k) marketing such class III devices during
jstallworth on DSK7TPTVN1PROD with PROPOSALS

notification requirements. Elsewhere in In accordance with section 515(b) of FDA’s review of the PMA provided that
this issue of the Federal Register, FDA the FD&C Act, FDA is proposing to the PMA is timely filed. FDA intends to
is announcing the availability of a draft require that a PMA be filed with the review any PMA for the device within
guidance document entitled Agency within 90 days after issuance of 180 days of the date of filing. FDA
‘‘Electroconvulsive Therapy (ECT) any final order based on this proposal cautions that under section
Devices for Class II Intended Uses,’’ for ECT devices intended for Certain 515(d)(1)(B)(i) of the FD&C Act, the
that, when finalized, would provide Specified Intended Uses. An applicant Agency may not enter into an agreement
recommendations on how to comply whose device was legally in commercial to extend the review period for a PMA

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81230 Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules

beyond 180 days unless the Agency ECT device for these uses must submit B. Summary of Data
finds that ‘‘the continued availability of an amendment to their previously For intended uses other than the
the device is necessary for the public cleared premarket notification (510(k)) treatment of MDE associated with MDD
health.’’ that demonstrates compliance with the or BPD in patients 18 years of age and
FDA intends that under § 812.2(d), the special controls within 60 days after the older who are treatment-resistant or
preamble to any final order based on effective date of the final order. Such who require a rapid response due to the
this proposal will state that, as of the amendment will be added to the 510(k) severity of their psychiatric or medical
date on which the filing of a PMA or a file but will not serve as a basis for a condition, FDA concludes that the
notice of completion of a PDP is new substantial equivalence review. A safety and effectiveness of ECT devices
required to be filed, the exemptions submitted 510(k) amendment in this have not been established by adequate
from the requirements of the IDE context will be used solely to scientific evidence. Given the FDA
regulations for preamendments class III demonstrate to FDA that an ECT device analysis and the advisory panel
devices in § 812.2(c)(1) and (2) will is in compliance with the special deliberations (see http://www.fda.gov/
cease to apply to any device that is: (1) controls. If a 510(k) amendment is not AdvisoryCommittees/
Not legally on the market on or before submitted within 60 days after the CommitteesMeetingMaterials/
that date or (2) legally on the market on effective date or if FDA determines that MedicalDevices/
or before that date but for which a PMA the amendment does not demonstrate MedicalDevicesAdvisoryCommittee/
or notice of completion of a PDP is not compliance with the special controls, NeurologicalDevicesPanel/
filed by that date, or for which PMA the device may be considered ucm240924.htm), there is insufficient
approval has been denied or withdrawn. adulterated under section 501(f)(1)(B) of
If a PMA for a class III device is not evidence of effectiveness for indications
the FD&C including: schizophrenia, bipolar mania
filed with FDA within 90 days after the
date of issuance of any final order X. Proposed Findings With Respect to (and mixed states), schizoaffective
requiring premarket approval for the Risks and Benefits disorder, schizophreniform disorder,
device, the device would be deemed and catatonia. The panel recommended
adulterated under section 501(f) of the As required by section 515(b) of the Class III designation for schizophrenia,
FD&C Act (21 U.S.C. 351(f)). The device FD&C Act, FDA is publishing its bipolar mania (and mixed states),
may be distributed for investigational proposed findings regarding: (1) The schizoaffective disorder, and
use only if the requirements of the IDE degree of risk of illness or injury schizophreniform disorder; however,
regulations are met. The requirements designed to be eliminated or reduced by the panel did not reach consensus on
for significant risk devices include requiring that this device have an the classification of ECT in treatment of
submitting an IDE application to FDA approved PMA or a declared completed catatonia and a review of the literature
for its review and approval. An PDP when intended for use in treating for use of ECT in catatonia yielded only
approved IDE is required to be in effect any condition other than MDE one randomized control trial (Ref. 11).
before an investigation of the device associated with MDD or BPD in patients The body of evidence is not sufficiently
may be initiated or continued under 18 years of age and older who are robust for FDA to determine that there
§ 812.30. FDA, therefore, cautions that treatment-resistant or who require a is a reasonable assurance of safety and
IDE applications should be submitted to rapid response due to the severity of effectiveness for ECT treatment of
FDA at least 30 days before the end of their psychiatric or medical condition catatonia. Catatonia is a potentially life-
the 90-day period after the issuance of and (2) the benefits to the public from threatening condition for patients
the final order to avoid interrupting the use of ECT devices for other unresponsive to the current standard of
investigations. specified intended uses. care treatment. FDA encourages
FDA proposes that following the These findings are based on the collection of additional data that may
effective date of any final order, ECT reports and recommendations of the support future reclassification of ECT
devices intended for use in treating advisory committees (panels) for the for this use.
severe MDE associated with MDD and classification of these devices along FDA believes that insufficient
BPD in patients 18 years of age and with information submitted in response information exists regarding the risks
older who are treatment-resistant or to the 515(i) Order (74 FR 16214), the and benefits of the device in order for
who require a rapid response due to the public docket (74 FR 46607) and any FDA to determine that general and/or
severity of their psychiatric or medical additional information that FDA has special controls will provide reasonable
condition must comply with the special obtained. Additional information assurance of the safety and effectiveness
controls. FDA notes that a firm whose regarding the risks as well as of ECT for Certain Specified Intended
ECT device was legally in commercial classification associated with this Uses. As established in section
distribution before May 28, 1976, or device type can be found in 43 FR 513(a)(1)(C) of the FD&C Act and 21
whose device was found to be 55729, 44 FR 51776, 48 FR 14758, and CFR 860.3(c)(3), a device is in class III
substantially equivalent to such a device 55 FR 36578. if insufficient information exists to
and who does not intend to market such determine that general controls and/or
device for uses other than use in treating XI. Device Subject to the Proposal To special controls are sufficient to provide
severe MDE associated with MDD and Require a PMA—ECT Devices for reasonable assurance of its safety and
BPD in patients 18 years of age and Certain Specified Intended Uses effectiveness and the device is
older who are treatment-resistant or (§ 882.5940(c)) purported or represented to be for a use
jstallworth on DSK7TPTVN1PROD with PROPOSALS

who require a rapid response due to the A. Identification that is life-supporting or life-sustaining,
severity of their psychiatric or medical or for a use which is of substantial
condition, may remove such intended An electroconvulsive therapy device importance in preventing impairment of
uses from the device’s labeling. FDA is a device used for treating severe human health, or if the device presents
proposes that such ECT devices must psychiatric disturbances by inducing in a potential unreasonable risk of illness
comply with the special controls, and, the patient a major motor seizure by or injury. FDA believes that the risks to
as part of the special controls, anyone applying a brief intense electrical health identified in section V for the use
who wishes to continue to market an current to the patient’s head. of ECT devices for Certain Specified

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81232 Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules

XIX. References 10. Girish, K., N.S. Gill, ‘‘Electroconvulsive features built into the device including
Therapy in Lorazepam Non-Responsive the static and dynamic impedance
The following references are on Catatonia.’’ Indian Journal of Psychiatry:
display in the Division of Dockets monitoring system.
45(1):21–25, 2003. (v) Appropriate analysis/testing must
Management (see ADDRESSES) and are 11. FDA Executive Summary, Prepared for
available for viewing by interested the January 27–28, 2011 meeting of the validate electromagnetic compatibility.
persons between 9 a.m. and 4 p.m., Neurological Devices Panel, Meeting to (vi) Appropriate software verification,
Monday through Friday; they are also Discuss the Classification of validation, and hazard analysis must be
available electronically at http:// Electroconvulsive Therapy Devices (ECT), performed.
www.regulations.gov. FDA has verified available at http://www.fda.gov/ (vii) Performance data must
AdvisoryCommittees/ demonstrate electrical performance,
the Web site addresses, as of the date
CommitteesMeetingMaterials/ adhesive integrity, and physical and
this document publishes in the Federal MedicalDevices/
Register, but Web sites are subject to chemical stability of the stimulation
MedicalDevicesAdvisoryCommittee/ electrodes.
change over time. NeurologicalDevicesPanel/ucm240924.htm.
(viii) The labeling for the device must
1. American Psychiatric Association. 2001. List of Subjects in 21 CFR Part 882 include the following:
The Practice of Electroconvulsive Therapy: (A) Information related to generic
Recommendations for Treatment, Training Medical devices, Neurological
and Privileging—A Task Force Report, 2nd devices. adverse events associated with ECT
ed. American Psychiatric Press, Washington, Therefore, under the Federal Food, treatment.
DC. Drug, and Cosmetic Act and under (B) Instructions must contain the
2. Royal College of Psychiatrists. The ECT authority delegated to the Commissioner following specific recommendations to
Handbook. Ed. A.I.F. Scott. The Third Report the user of the device:
of the Royal College of Psychiatrists’ Special
of Food and Drugs, it is proposed that
21 CFR part 882 be amended as follows: (1) Conduct of pre-ECT medical and
Committee on ECT. 2004. Available at: http:// psychiatric assessment (including
www.ectron.co.uk/ws-public/uploads/143_ pertinent medical and psychiatric
cr128.pdf PART 882—NEUROLOGICAL DEVICES
3. NICE (National Institute for Health and history, physical examination,
Clinical Excellence). Guidance on the Use of ■ 1. The authority citation for 21 CFR anesthesia assessment, dental
Electroconvulsive Therapy. Technology part 882 continues to read as follows: assessment, and other studies as
Appraisal Guidance: 59:1–37, 2003. Authority: 21 U.S.C. 351, 360, 360c, 360e, clinically appropriate);
Available at: https://www.nice.org.uk/ 360j, 371. (2) Use of patient monitoring during
guidance/ta59 the procedure;
4. NICE (National Institute for Health and ■ 2. Revise § 882.5940 to read as
follows: (3) Use of general anesthesia and
Clinical Excellence). Depression in Adults neuromuscular blocking agents;
(update). National Clinical Practice
Guideline: 90:1–585, 2009. Available at:
§ 882.5940 Electroconvulsive therapy (4) Use of mouth/dental protection
device. during the procedure;
https://www.nice.org.uk/guidance/cg90
5. U.S. Department of Health and Human (a) Identification. An (5) Use of EEG monitoring until
Services. Mental Health: A Report of the electroconvulsive therapy device is a seizure termination;
Surgeon General. Rockville, MD: Substance prescription device, including the pulse (6) Instructions on electrode
Abuse and Mental Health Services generator and its stimulation electrodes placement, including adequate skin
Administration/Center for Mental Health and accessories, used for treating severe preparation and use of conductivity gel;
Services; National Institutes of Health/ and
National Institute of Mental Health, 1999.
psychiatric disturbances by inducing in
Available at: http://profiles.nlm.nih.gov/ps/ the patient a major motor seizure by (7) Cognitive status monitoring prior
retrieve/ResourceMetadata/NNBBHS applying a brief intense electrical to beginning ECT and during the course
6. Semkovska, M., D.M. McLoughlin, current to the patient’s head. of treatment via formal
‘‘Objective Cognitive Performance Associated (b) Classification. (1) Class II (special neuropsychological assessment for
with Electroconvulsive Therapy for controls) when the device is intended to evaluating specific cognitive functions
Depression: A Systematic Review and Meta- treat severe major depressive episodes (e.g., orientation, attention, memory,
Analysis.’’ Biological Psychiatry: 68:568–577, (associated with major depressive executive function).
2010. (C) Clinical training needed by users
7. Greenhalgh, J., C. Knight, D. Hind, C.
disorder or bipolar disorder) in patients
Beverley, S. Walters, ‘‘Clinical and Cost- 18 years of age and older who are of the device.
effectiveness of Electroconvulsive Therapy treatment-resistant or who require a (D) Information on the patient
for Depressive Illness, Schizophrenia, rapid response due to the severity of population in which the device is
Catatonia and Mania: Systematic Reviews their psychiatric or medical condition. intended to be used.
and Economic Modelling Studies. Health The special controls for this device are: (E) Information on how the device
Technology Assessment: 9(9):1–170, 2005. (i) The technical parameters of the operates and the typical course of
J.C. Fournier, R.J. DeRubeis, S.D. Hollon, S. device, including waveform, output treatment.
Dimidjian, J.D. Amsterdam, R.C. Shelton, J. (F) A detailed summary of the clinical
Fawcett, ‘‘Antidepressant Drug Effects and
mode, pulse duration, frequency, train
Depression Severity.’’ Journal of the delivery, maximum charge and energy, testing, which includes the clinical
American Medical Association: 303(1):47–53, and the type of impedance monitoring outcomes associated with the use of the
2010. system must be fully characterized. device, and a summary of adverse
8. Kirsch, I., B.J. Deacon, T.B. Huedo- (ii) Non-clinical testing data must events and complications that occurred
Medina, A. Scoboria, T.J. Moore, B.T. confirm the electrical characteristics of with the device.
jstallworth on DSK7TPTVN1PROD with PROPOSALS

Johnson, ‘‘Initial Severity and Antidepressant the output waveform. (G) A detailed summary of the device
Benefits: A Meta-analysis of Data Submitted (iii) Components (and accessories) of technical parameters;
to the Food and Drug Administration.’’ PLoS the device that come into human (H) Where appropriate, validated
Medicine: 5(2):260–268, 2008.
9. Watts, B.V., et al. ‘‘An Examination of
contact must be demonstrated to be methods and instructions for
Mortality and Other Adverse Events Related biocompatible. reprocessing of any reusable
to Electroconvulsive Therapy Using a (iv) Performance data must components.
National Adverse Event Report System.’’ demonstrate electrical and mechanical (I) The following statement,
Journal of ECT, 2010. safety and the functioning of all safety prominently placed: ‘‘Warning: ECT

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Federal Register / Vol. 80, No. 249 / Tuesday, December 29, 2015 / Proposed Rules 81233

device use may be associated with: talkativeness, and decreased need for Dated: December 18, 2015.
disorientation, confusion, and memory sleep) or a worsening of the psychiatric Leslie Kux,
problems.’’ symptoms they are being treated for. Associate Commissioner for Policy.
(J) Absent performance data (3) The physical risks of ECT may [FR Doc. 2015–32592 Filed 12–28–15; 8:45 am]
demonstrating a beneficial effect of include the following (in order of BILLING CODE 4164–01–P
longer term use, generally considered frequency of occurrence):
treatment in excess of 3 months, the (i) Pain/somatic discomfort (including
following statement, prominently headache, muscle soreness, and nausea). DEPARTMENT OF HEALTH AND
placed: ‘‘Warning: When used as (ii) Skin burns. HUMAN SERVICES
intended this device provides short- (iii) Physical trauma (including
term relief of symptoms. The long-term fractures, contusions, injury from falls, Food and Drug Administration
safety and effectiveness of ECT dental and oral injury).
treatment has not been demonstrated.’’ (iv) Prolonged or delayed onset 21 CFR Part 1271
(ix) Patient labeling must be provided seizures. [Docket No. FDA–2015–D–3719]
and include: (v) Pulmonary complications
(A) Relevant contraindications, (insufficient, or lack of breathing, or Draft Guidances Relating to the
warnings, precautions. inhalation of foreign substance into the Regulation of Human Cells, Tissues, or
(B) A summation of the clinical lungs). Cellular or Tissue-Based Products;
testing, which includes the clinical (vi) Cardiovascular complications Public Hearing; Request for
outcomes associated with the use of the (heart attack, high or low blood Comments; Correction
device, and a summary of adverse pressure, and stroke).
events and complications that occurred (vii) Death. AGENCY: Food and Drug Administration,
with the device. (viii) Devices marketed prior to the HHS.
(C) Information on how the device ACTION: Notification of public hearing;
effective date of this reclassification
operates and the typical course of request for comments; correction.
must have an amendment submitted to
treatment.
(D) The potential benefits. their previously cleared premarket
SUMMARY: The Food and Drug
(E) Alternative treatments. notification (510(k)) that demonstrates
Administration (FDA or Agency) is
(F) The following statement, compliance with these special controls
correcting a notification of a public
prominently placed: ‘‘Warning: ECT within 60 days after the effective date of
hearing entitled ‘‘Draft Guidances
device use may be associated with: this reclassification.
Relating to the Regulation of Human
disorientation, confusion, and memory (2) Classification: Class III (premarket
Cells, Tissues, or Cellular or Tissue-
problems.’’ approval) for the following intended
Based Products; Public Hearing; Request
(G) Absent performance data uses: schizophrenia, bipolar manic
for Comments’’ that appeared in the
demonstrating a beneficial effect of states, schizoaffective disorder,
Federal Register of October 30, 2015 (80
longer term use, generally considered schizophreniform disorder, and
FR 66845). The document announced a
treatment in excess of 3 months, the catatonia.
public hearing to obtain input on four
following statement, prominently (c) Date premarket approval
recently issued draft guidances relating
placed: ‘‘Warning: When used as application (PMA) or notice of
to the regulation of human cells, tissues,
intended this device provides short- completion of product development
or cellular or tissue-based products
term relief of symptoms. The long-term protocol (PDP) is required. A PMA or
(HCT/Ps). The document published
safety and effectiveness of ECT notice of completion of a PDP is
with conflicting information about who
treatment has not been demonstrated.’’ required to be filed with the Food and
must register for the public hearing.
(H) The following statements on Drug Administration on or before [A
This document corrects that error.
known risks of ECT, absent performance DATE WILL BE ADDED 90 DAYS
AFTER DATE OF PUBLICATION OF A FOR FURTHER INFORMATION CONTACT: Lori
data demonstrating that these risks do
FUTURE FINAL ORDER IN THE Jo Churchyard, Center for Biologics
not apply:
(1) ECT treatment may be associated Federal Register], for any Evaluation and Research, Food and
with disorientation, confusion and electroconvulsive therapy device with Drug Administration, 10903 New
memory loss, including short-term an intended use described in paragraph Hampshire Ave., Bldg. 71, Rm. 7301,
(anterograde) and long-term (b)(2) of this section, that was in Silver Spring, MD 20993, 240–402–
(autobiographical) memory loss commercial distribution before May 28, 7911.
following treatment. These side effects 1976, or that has, on or before [A DATE SUPPLEMENTARY INFORMATION: In FR Doc.
tend to go away within a few days to a WILL BE ADDED 90 DAYS AFTER 2015–27703, appearing on pages 66845
few months after the last treatment with DATE OF PUBLICATION OF A and 66847 in the Federal Register of
ECT. However, some patients have FUTURE FINAL ORDER IN THE Friday, October 30, 2015, the following
reported a permanent loss of memories Federal Register], been found to be corrections are made:
of personal life events (i.e., substantially equivalent to any 1. On page 66845, in the third column
autobiographical memory). electroconvulsive therapy device with under DATES, the third sentence is
Improvements in the way ECT is an intended use described in paragraph revised to read: ‘‘Persons seeking to
applied to patients currently, with (b)(2) of this section, that was in attend (including FDA employees) or to
jstallworth on DSK7TPTVN1PROD with PROPOSALS

controlled electric currents and commercial distribution before May 28, present at the public hearing must
electrode placement, can minimize but 1976. Any other electroconvulsive register by January 8, 2016.’’
not completely eliminate, these risks. therapy device with an intended use 2. On page 66847, in the first column
(2) Patients treated with ECT may also described in paragraph (b)(2) of this under section IV. Attendance and
experience manic symptoms (including section shall have an approved PMA or Registration, the third sentence is
euphoria and/or irritability, impulsivity, declared completed PDP in effect before revised to read: ‘‘Individuals who wish
racing thoughts, distractibility, being placed in commercial to attend (including FDA employees) or
grandiosity, increased activity, distribution. present at the public hearing must

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Document Created: 2015-12-29 10:15:05
Document Modified: 2015-12-29 10:15:05

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Proposed Rules
Action		Proposed order.
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.
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, 301-796-6283, [email protected]
FR Citation		80 FR 81223
CFR Associated		Medical Devices and Neurological Devices

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 249 (December 29, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration