[Federal Register Volume 80, Number 249 (Tuesday, December 29, 2015)]
[Proposed Rules]
[Pages 81223-81233]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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, 
[email protected].

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