Effective Date of Requirement for Premarket Approval for Three Class III Preamendments Devices; Reclassification of Sorbent Hemoperfusion Devices for the Treatment of Poisoning and Drug Overdose, 20268-20277 [2013-07730]

Agencies

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

[Federal Register Volume 78, Number 65 (Thursday, April 4, 2013)]
[Proposed Rules]
[Pages 20268-20277]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-07730]


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Proposed Rules
                                                Federal Register
________________________________________________________________________

This section of the FEDERAL REGISTER contains notices to the public of 
the proposed issuance of rules and regulations. The purpose of these 
notices is to give interested persons an opportunity to participate in 
the rule making prior to the adoption of the final rules.

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Federal Register / Vol. 78, No. 65 / Thursday, April 4, 2013 / 
Proposed Rules

[[Page 20268]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 876, 882, and 892

[Docket No. FDA-2013-N-0195]


Effective Date of Requirement for Premarket Approval for Three 
Class III Preamendments Devices; Reclassification of Sorbent 
Hemoperfusion Devices for the Treatment of Poisoning and Drug Overdose

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed order.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is issuing a proposed 
administrative order to require the filing of a premarket approval 
application (PMA) or a notice of completion of a product development 
protocol (PDP) for the following three class III preamendments devices: 
Sorbent hemoperfusion devices for the treatment of hepatic coma and 
metabolic disturbances; cranial electrotherapy stimulator for the 
treatment of depression, anxiety, and insomnia; and transilluminator 
for breast evaluation. FDA is also announcing the opportunity for 
interested persons to request that the Agency change the classification 
of any of the aforementioned devices based on new information. In 
addition, FDA is proposing to reclassify sorbent hemoperfusion devices 
for the treatment of poisoning and drug overdose, a preamendments class 
III device, into class II (special controls) based on new information 
respecting the device. This action implements certain statutory 
requirements.

DATES: Submit written or electronic comments on this proposed order by 
May 6, 2013. FDA intends that, if a final order based on this proposed 
order is issued, anyone who wishes to continue to market the sorbent 
hemoperfusion devices for the treatment of hepatic coma and metabolic 
disturbances; cranial electrotherapy stimulator for the treatment of 
depression, anxiety, and insomnia; or transilluminator for breast 
evaluation will need to file a PMA or a notice of completion of a PDP 
within 90 days of the effective date of the final order. See section 
XIII of this document for the proposed effective date of any final 
order that may publish based on this proposed order.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-0195 by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following way:
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and Docket Number FDA-2013-N-0195 for this action. All comments 
received may be posted without change to https://www.regulations.gov, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Michael 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.

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 (Pub. L. 101-629), the 
Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L. 
105-115), the Medical Device User Fee and Modernization Act of 2002 
(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), among other amendments, 
established a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the FD&C Act (21 U.S.C. 
360c) established three categories (classes) of devices, reflecting the 
regulatory controls needed to provide reasonable assurance of their 
safety and effectiveness. The three categories of devices are class I 
(general controls), class II (special controls), and class III 
(premarket approval).
    Under section 513(d) of the FD&C Act, devices that were in 
commercial distribution before the enactment of the 1976 amendments, 
May 28, 1976 (generally referred to as preamendments devices), are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed 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

[[Page 20269]]

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 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 (both the preamendments and substantially 
equivalent devices are referred to as preamendments class III devices) 
may be marketed without submission of a PMA until FDA takes final 
action under section 515(b) of the FD&C Act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    Although, under the FD&C Act, the manufacturer of class III 
preamendments device may respond to the call for PMAs by filing a PMA 
or a notice of completion of a product development protocol (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(b) of FDASIA (126 
Stat. 1056) 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. Prior to the enactment of 
FDASIA, FDA published four proposed rules under section 515(b) to 
require PMAs for the sorbent hemoperfusion devices for the treatment of 
hepatic coma and metabolic disturbances; cranial electrotherapy 
stimulator for the treatment of depression, anxiety, and insomnia; 
shortwave diathermy for all uses other than the generation of deep heat 
within the body tissues for the treatment of selected medical 
conditions; and transilluminator for breast evaluation (76 FR 48062, 
August 8, 2011; 77 FR 9610, February 17, 2012; 77 FR 39953, July 6, 
2012; 75 FR 52294, August 25, 2010). FDA is issuing this proposed 
administrative order to comply with the new procedural requirement 
created by FDASIA when requiring premarket approval for preamendments 
class III devices. Shortwave diathermy for all uses other than the 
generation of deep heat within the body tissues for the treatment of 
selected medical conditions is not included in this proposed 
administrative order due to an approaching panel meeting on the 
classification of this device scheduled for April 5, 2013 (77 FR 71195, 
November 29, 2012). Because of the level of interest in the 
classification of shortwave diathermy for all uses other than the 
generation of deep heat within the body tissues for the treatment of 
selected medical conditions and because this technology was last 
considered by a panel December 13, 1979, FDA is electing to hold the 
panel meeting required by sections 513(e) and 515(b) of the FD&C Act 
before issuing a proposed order on this device. FDA believes a new 
panel meeting will be useful to consider significant new developments 
in the technology class III shortwave diathermy devices use since that 
time and the large volume of new information on the use of these 
devices. In addition, the 1979 Panel's deliberations focused on class 
II shortwave diathermy devices that achieve their affect through use of 
therapeutic deep heat instead of those class III shortwave diathermy 
devices that are the subject of FDA's July 6, 2012, proposed rule.
    Comments submitted in response to the proposed rules on sorbent 
hemoperfusion devices for the treatment of hepatic coma and metabolic 
disturbances; cranial electrotherapy stimulator for the treatment of 
depression, anxiety, and insomnia; and transilluminator for breast 
evaluation will be considered under this proposed administrative order 
and do not need to be resubmitted. Similarly, FDA continues to review 
the merits of the requests for reclassification submitted in response 
to the proposed rules. Any preliminary decisions on those requests are 
not reflected in this proposed administrative order to require the 
filing of a PMA for sorbent hemoperfusion devices for the treatment of 
hepatic coma and metabolic disturbances; cranial electrotherapy 
stimulator for the treatment of depression, anxiety, and insomnia; and 
transilluminator for breast evaluation. This action is intended solely 
to fulfill the procedural requirements for reclassification implemented 
by FDASIA.
    Section 515(b)(1) of the FD&C Act sets forth the process for 
issuing a final administrative order. Specifically, prior to the 
issuance of a final order requiring premarket approval for a 
preamendments class III device, the following must occur: Publication 
of a proposed order in the Federal Register; a meeting of a device 
classification panel described in section 513(b) of the FD&C Act; and 
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 cranial electrotherapy stimulator for the treatment of 
depression, anxiety, and insomnia and transilluminator for breast 
evaluation, 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 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. 360(f).
    A preamendments class III device may be commercially distributed 
without a PMA until 90 days after FDA issues a final order (a final 
rule issued under section 515(b) of the FD&C Act prior to the enactment 
of FDASIA is considered to be a final order for purposes of section 
501(f) of the FD&C Act (21 U.S.C. 351(f))) 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 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 the 
sorbent hemoperfusion devices for the treatment of hepatic coma and 
metabolic disturbances; cranial electrotherapy stimulator for the 
treatment of depression, anxiety, and insomnia; and transilluminator 
for breast evaluation were classified in 1983, 1979, and 1995, 
respectively, the 30-month period has

[[Page 20270]]

expired (48 FR 53028, November 23, 1983; 44 FR 51770, September 4, 
1979; and 60 FR 36639, July 18, 1995, respectively). Therefore, if the 
proposal to require premarket approval for sorbent hemoperfusion 
devices for the treatment of hepatic coma and metabolic disturbances; 
cranial electrotherapy stimulator for the treatment of depression, 
anxiety, and insomnia; or transilluminator for breast evaluation 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) of the FD&C Act, interested 
persons are being offered the opportunity to request reclassification 
of sorbent hemoperfusion devices for the treatment of hepatic coma and 
metabolic disturbances; cranial electrotherapy stimulator for the 
treatment of depression, anxiety, and insomnia; and transilluminator 
for breast evaluation that are the subject of this proposal. Requests 
for reclassification previously submitted in response to the proposed 
rules (76 FR 48062, August 8, 2011; 75 FR 52294, August 25, 2010; 77 FR 
9610, February 17, 2012) will be considered under this proposed 
administrative order and do not need to be resubmitted.
    Along with proposing to require PMAs for sorbent hemoperfusion 
devices for the treatment of hepatic coma and metabolic disturbances; 
cranial electrotherapy stimulator for the treatment of depression, 
anxiety, and insomnia; and transilluminator for breast evaluation, FDA 
is also publishing this document to propose the reclassification of 
sorbent hemoperfusion devices for the treatment of poisoning and drug 
overdose 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) 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 action where the reevaluation is made 
in light of newly available authority (see Bell, 366 F.2d at 181; 
Ethicon, Inc. v. FDA, 762 F. Supp. 382, 388-91 (D.D.C. 1991)), or in 
light of changes in ``medical science'' (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 21 CFR 860.7(c)(2). (See, e.g., General Medical Co. v. 
FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Association 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 (21 U.S.C. 360j(c)).) Section 
520(h)(4) of the FD&C Act (21 U.S.C. 360j(h)(4)), 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.
    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 preamendments class III device from rulemaking to 
an administrative order. Prior to the enactment of FDASIA, FDA 
published a proposed rule under section 513(e) proposing the 
reclassification of sorbent hemoperfusion devices for the treatment of 
poisoning and drug overdose. The same device is the subject of this 
proposed order so that FDA can comply with the new procedural 
requirement created by FDASIA when reclassifying a preamendments class 
III device.
    Section 513(e)(1) of the FD&C Act sets forth the process for 
issuing a final order. 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.
    FDAMA added 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.

II. 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 for three preamendments 
class III devices, sorbent hemoperfusion devices for the treatment of 
hepatic coma and metabolic disturbances; cranial electrotherapy 
stimulator for the

[[Page 20271]]

treatment of depression, anxiety, and insomnia; and transilluminator 
for breast evaluation, within 90 days after issuance of any final order 
based on this proposal. 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 device during FDA's 
review of the PMA provided that the PMA is timely filed. FDA intends to 
review any PMA for the device within 180 days of the date of filing. 
FDA cautions that under section 515(d)(1)(B)(i) of the FD&C Act, the 
Agency may not enter into an agreement to extend the review period for 
a PMA beyond 180 days unless the Agency finds that ``the continued 
availability of the device is necessary for the public health.''
    FDA intends that under Sec.  812.2(d), the publication in the 
Federal Register of any final order based on this proposal will include 
a statement that, as of the date on which a PMA 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 (c)(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 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. 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 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, recommends 
that IDE applications 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 any ongoing investigations.
    Because sorbent hemoperfusion devices for the treatment of 
poisoning and drug overdose can currently be marketed after receiving 
clearance of an application for premarket notification and FDA is 
proposing to reclassify these devices as class II requiring clearance 
of an application for premarket notification, this order, if finalized, 
will not impose any new requirements on sorbent hemoperfusion devices 
for the treatment of poisoning and drug overdose.

III. Proposed Findings With Respect to Risks and Benefits for Devices 
Subject to the Proposal To Require PMA

    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 these 
devices have an approved PMA and (2) the benefits to the public from 
the use of the devices.
    These findings are based on the reports and recommendations of the 
advisory committee (panel) for the classification of these devices 
along with information submitted in response to the 515(i) Order (74 FR 
16214, April 9, 2009), and any additional information that FDA has 
obtained. Additional information regarding the risks as well as 
classification associated with these device types can be found in the 
following proposed and final rules and notices published in the Federal 
Register: Cranial electrotherapy stimulator for the treatment of 
depression, anxiety, and insomnia, 43 FR 55716 (November 28, 1974), 44 
FR 51770 (September 4, 1979), 54 FR 550 (January 6, 1989), 58 FR 45865 
(August 31, 1993), 60 FR 43967 (August 24, 1995), 61 FR 59448 (November 
22, 1996), 62 FR 4023 (January 28, 1997), 62 FR 30456 and 62 FR 30600 
(June 4, 1997), and 76 FR 48062 (August 8, 2011); classification of 
transilluminators (Diaphanoscopes or Lightscanners) for breast 
evaluation, 60 FR 3168 (January 13, 1995), 60 FR 36639 (July 18, 1995), 
and 75 FR 52294, (August 25, 2010); and sorbent hemoperfusion for the 
treatment of hepatic coma and metabolic disturbances (46 FR 7630, 46 FR 
7562, and 48 FR 53023).
    The proposed findings concerning the degree of risk of illness or 
injury for each of these devices is set out in section IV, as well as 
information concerning known benefits, if any for these devices. FDA 
notes, however, that there is limited scientific evidence regarding the 
effectiveness of the sorbent hemoperfusion devices for the treatment of 
hepatic coma and metabolic disturbances; cranial electrotherapy 
stimulator for the treatment of depression, anxiety, and insomnia; and 
transilluminator for breast evaluation devices. Because the benefits of 
these devices for the indications specified are unknown, it is 
impossible to estimate the direct effect of the devices on patient 
outcomes. However, claims for the devices state the devices have the 
potential to benefit the public in the following ways:
     Cranial electrotherapy stimulator for the treatment of 
depression, anxiety, and insomnia. CES devices are marketed as a 
treatment for insomnia, anxiety, or depression (either symptoms thereof 
or the underlying disorder).
     Sorbent hemoperfusion devices for the treatment of hepatic 
coma and metabolic disturbances. Disorders that affect the liver can 
result in metabolic disturbances and a decrease in brain function due 
to the accumulation of toxins in the blood. This reduced brain function 
may eventually result in hepatic coma and death. Sorbent hemoperfusion 
systems are marketed as a treatment device to compensate for liver 
failure by removing toxins from the blood.
     Transilluminator for breast evaluation. Transilluminator 
for breast evaluation is marketed as an aid in breast self examination 
as an addition to normal breast health routine by visualizing 
translucent tissue for the diagnosis of cancer, other conditions, 
diseases, or abnormalities.

IV. Devices Subject to the Proposal To Require PMA

A. Sorbent Hemoperfusion System for the Treatment of Hepatic Coma and 
Metabolic Disturbances (21 CFR 876.5870(c))

1. Identification
    A sorbent hemoperfusion system is a device that consists of an 
extracorporeal blood system and a container filled with adsorbent 
material that removes a wide range of substances, both toxic and 
normal, from blood flowing through it. The adsorbent materials are 
usually activated-carbon or resins, which may be coated or immobilized 
to prevent fine particles entering the patient's blood. The generic 
type of device may include lines and filters specifically designed to 
connect the device to the extracorporeal blood system. Sorbent 
hemoperfusion systems may also include the machine or instrument used 
to drive and manage blood and fluid flow within the extracorporeal 
circuit, as well as any accompanying controllers, monitors, or sensors.
2. Summary of Data
    For the treatment of hepatic coma and metabolic disturbances, FDA 
concludes that the safety and effectiveness of these devices have not 
been established by adequate scientific evidence, and the Agency 
continues to agree with the Gastroenterology-Urology Device Panel's 
recommendation. The review of the published scientific literature

[[Page 20272]]

revealed mostly observational studies performed with sorbent 
hemoperfusion devices. Only a few randomized, controlled trials were 
found, but sample sizes were small and not adequately powered, and 
etiologies and control group criteria were varied. Furthermore, based 
on FDA's experience reviewing these devices for use in the treatment of 
hepatic coma and metabolic disturbances, bench testing is not adequate 
in establishing the devices' safety and effectiveness, particularly 
since characterizing a sorbent hemoperfusion system's performance and 
adsorption capabilities has not correlated to patient outcomes, such as 
resolution of the patients' hepatic coma, or improvements in mortality. 
The scientific literature also revealed that there is no consensus on 
the clinical endpoints necessary to adequately evaluate sorbent 
hemoperfusion devices for the treatment of hepatic coma and metabolic 
disturbances or on the patient populations who will benefit the most 
from the use of these devices.
3. Risks to Health
     Extracorporeal leaks (blood loss)--Rupture of the 
extracorporeal circuit, cartridge, filters, and/or tubing, as well as 
disconnections, may lead to blood leaks and blood loss.
     Platelet loss and thrombocytopenia--The adsorption 
characteristics of the device may cause large losses of platelets 
during hemoperfusion.
     Leukopenia--The materials used, or the design of the 
device, may cause absorption of leukocytes, leading to the transient 
loss of leukocytes in a patient.
     Hemolysis--The materials used, or the design of the blood 
pathways in the device, may cause the lysis of red blood cells.
     Leak of adsorbent agent into fluid path (release of 
emboli)--Fine particles leached from the sorbent column of the device 
may be deposited in the arterioles of the lungs and other organ as 
particulate emboli.
     Lack of sterility--Improper sterilization or compromise of 
the device packaging may lead to the introduction of microorganisms, 
which may be transmitted to a patient during use.
     Toxic and/or pyrogenic reactions--Toxic substances may be 
leached from the device, causing a patient to have a pyrogenic reaction 
(sudden fever with collapse and chills).
     Infection--Defects in the design or construction of the 
device preventing adequate cleaning and/or sterilization may allow 
pathogenic organisms to be introduced and may cause an infection in a 
patient.
     Hypotension--Sudden fluid shifts within the patient, due 
to pressures exerted by the device, or to fluid being removed by the 
device, may cause sudden decreases in a patient's blood pressure.
     Lack of biocompatibility in materials or solutions 
contacting blood--The patient-contacting materials of the device may 
cause an adverse immunological or allergic reaction in a patient.
     Clotting (blood loss)--The materials used, or the design 
of the device, may cause a patient's blood to form clots, which may 
obstruct the device's extracorporeal circuit, interrupting or 
terminating treatments, and also leading to blood loss, because the 
blood entrapped in the clotted blood circuit often cannot be returned 
to the patient.
     Removal or depletion of vital nutrients, hormones, 
vitamins, substances. and drugs (e.g., adsorption of glucose, 
unspecific removal characteristics, drop in patients' hematocrit), due 
to device's lack of specificity--The adsorption characteristics of the 
device may cause removal or depletions of nutrients, hormones, and 
other necessary substances.
     Metabolic disturbances--The removal of normal metabolites 
along with undesirable substances may lead to metabolic disturbances.
     Lack of effectiveness--The adsorption characteristics of 
the device may lead to the failure to remove drugs in the treatment of 
poisoning or drug overdose, or to bring on clinical improvement in 
hepatic coma and metabolic disturbances.
     Treatment interruptions or discontinuations--Inadequate 
safeguards in the device may lead to treatment interruptions or 
discontinuations in the case of power failures.
     Electrical shock due to lack of electrical safety--
Inadequate safeguards in the device may lead to electrical shocks in 
patients using them.
     Electromagnetic interference, which may lead to adverse 
interactions with other patient systems--Inadequate safeguards in the 
device may lead to its interference with other patient systems, causing 
adverse events in the patient, as well as adversely affecting the 
performance of the other patient systems.

B. Cranial Electrotherapy Stimulator (21 CFR 882.5800)

1. Identification
    A cranial electrotheraphy stimulator is a device that applies 
electrical current to a patient's head to treat depression, anxiety, or 
insomnia.
2. Summary of Data
    The Neurological Devices Panel that discussed original 
classification for the cranial electrotherapy stimulator (CES) device 
in 1977 and 1978 ultimately recommended that the device be classified 
into class III because satisfactory device effectiveness had not been 
demonstrated. The panel considered information from the National 
Research Council, which reviewed 88 published studies on CES and 
concluded that the device has not been shown to be effective in 
treating any of the conditions for which it was prescribed. In 
addition, the panel indicated that it was not possible to establish an 
adequate performance standard for CES because the characteristics of 
the electrical current necessary for potential effectiveness were not 
known. The panel believed that general controls would not provide 
sufficient control over these characteristics, and that the device 
presented a potential unreasonable risk of illness or injury to the 
patient if the practitioner relied on the device, and it was 
ineffective in treating the patient's illness. Therefore, the panel 
recommended that premarket approval was necessary to assure the safety 
and effectiveness of CES devices.
    In support of a subsequent proposed rule in 1993 for classification 
of CES into class III, FDA performed a literature review and identified 
additional studies that had been performed for CES. After a review of 
the scientific literature, FDA concluded that the effectiveness of CES 
had still not been established by adequate scientific evidence. While 
this rule was finalized in 1995 (60 FR 43969), it was withdrawn in 1997 
(62 FR 30456). FDA performed additional literature searches for studies 
of CES published after the 1993 proposed rule in support of the 
proposed rule to retain CES devices in class III and a call for PMAs 
issued on August 8, 2011 (76 FR 48062), as well as in preparation for 
the panel meeting described in the paragraphs that follow.
    FDA received three petitions requesting a change in the 
classification of CES devices in response to the August 8, 2011, 
proposed rule (76 FR 48062). FDA received a petition from 
Electromedical Products International, Inc., dated August 19, 2011 
[FDA-2011-

[[Page 20273]]

N-0504-0029], requesting the Agency to reclassify from class III into 
class II the CES for the ``treatment of insomnia, depression, or 
anxiety.'' FDA received petitions from Fisher Wallace Laboratories, 
LLC, dated August 22, 2011 [FDA-2011-N-0504-0031], and Neuro-Fitness 
LLC, dated August 22, 2011 [FDA-2011-N-0504-0033], both requesting the 
Agency to reclassify from class III into class II the CES for the 
``treatment of depression, anxiety, and insomnia in adult substance 
abuse patients who have failed to achieve satisfactory improvement from 
one prior antidepressant or sleep medication at or above the minimal 
effective dose and duration in the current episode, or are unable to 
tolerate such medication.'' The petition from Neuro-Fitness also 
mentioned ``general treatment of anxiety, depression, and insomnia as 
part of an approved program of medical care when conventional 
approaches have failed or are deemed inappropriate'' and ``treatment of 
the primary symptoms of substance abuse: Anxiety, depression, and 
insomnia when conventional approaches have failed or are deemed 
inappropriate.'' FDA continues to review the merits of the previous 
requests for reclassification submitted in response to the proposed 
rules and any preliminary decisions on those requests are not reflected 
in this proposed administrative order proposing to require the filing 
of a PMA for the cranial electrotherapy stimulator device for the 
treatment of depression, anxiety, and insomnia.
    Consistent with then-section 515(b)(2)(B) of the FD&C Act as it 
stood at the time and 21 CFR 860.125, FDA referred the petitions to the 
Panel for its recommendation on the requested change in classification 
in February 2012. FDA provided the panel members with the three 
reclassification petitions and FDA's executive summary (Ref. 1). Based 
on its review of the data and information as well as information 
presented during its February 10, 2012, open meeting (Ref. 2), the 
Neurological Devices Panel recommended that the CES device for 
treatment of insomnia, depression, and anxiety should remain in class 
III requiring PMAs. The Panel consensus was that there was not adequate 
scientific evidence to provide a reasonable assurance of effectiveness 
for the CES device for any of the indications proposed by the 
petitioners. Although the panel expressed some reservations regarding 
several of the risks that FDA had identified as being associated with 
CES, the Panel consensus was that given the lack of adequate 
effectiveness data, the probable benefits of the CES device did not 
outweigh the probable risks. The Panel also suggested that the list of 
risks in the proposed rule was not accurate. While there was consensus 
for including the risks of skin irritation, headaches, and dizziness, 
the panel did not agree that seizures and blurred vision were risks 
associated with CES as it is characterized today by the devices on the 
market and the comparable devices studied in clinical trials. The Panel 
also suggested that worsening of the condition being treated, though a 
risk, could be adequately addressed through patient supervision by a 
medical professional.
    While the panel did not recommend a classification for the focused 
indication in the substance abuse population for which two petitioners 
requested class II, the panel concluded that the substance abuse 
population did adequately define a target population and that there 
were no significant additional risks associated with use of the device 
in the substance abuse population as compared to the population of 
patients who are not substance abusers. The panel also recommended 
there was not adequate scientific evidence to provide a reasonable 
assurance of effectiveness for the CES device for treatment of 
insomnia, depression, or anxiety in the substance abuse population.
3. Risks to Health
     Worsening of the condition being treated--If the device is 
not effective and the patient is not treated in a conventional manner, 
the patient's psychological condition may worsen.
     Skin irritation--The electrodes or the conductive cream 
used with the electrodes may cause skin irritation.
     Headaches--Reported cases of adverse effects of CES 
devices include headaches following treatment with electrical 
stimulation.
     Potential adverse effects from electrical stimulation of 
the brain--The physiological effects associated with electrical 
stimulation of the brain by these devices have not been studied 
systematically; therefore, adverse effects which may be caused by these 
electrical stimuli remain unknown.

C. Transilluminator for Breast Evaluation (21 CFR 892.1990)

1. Identification
    A transilluminator, also known as a diaphanoscope or lightscanner, 
is an electrically powered device that uses low intensity emissions of 
visible light and near-infrared radiation (approximately 700-1050 
nanometers (nm)), transmitted through the breast, to visualize 
translucent tissue for the diagnosis of cancer, other conditions, 
diseases, or abnormalities.
2. Summary of Data
    On January 11, 1991, the Obstetrics and Gynecology Devices Panel 
recommended that transilluminator devices for breast evaluation be 
classified into class III and subject to premarket approval to provide 
reasonable assurance of the safety and effectiveness of the device. The 
panel concluded that there were no published studies or clinical data 
demonstrating the safety and effectiveness of the device. The panel 
indicated that the device presents a potential unreasonable risk of 
illness or injury to the patient if the clinician relies on the device 
and that although the device's illumination level, wavelength, and 
image quality can be controlled through tests and specifications, 
insufficient evidence exists to determine that special controls can be 
established to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use.
    In addition, the Radiologic Devices Panel considered the 
classification of the device on April 12, 2012 (Ref. 3), and expressed 
concerns regarding the effectiveness of the device which may result in 
delayed diagnosis and determined that general controls and special 
controls are not sufficient to provide a reasonable assurance of safety 
and effectiveness of the device for the diagnosis of cancer, other 
conditions, diseases, or abnormalities. Accordingly, the panel 
concluded that the device should remain in class III. FDA agreed and 
continues to agree with the recommendations of both panels and is aware 
of no information submitted in response to the 515(i) Order (74 FR 
16214, April 9, 2009) or otherwise available to FDA that would support 
a different classification. The Agency notes that the device has fallen 
into disuse and that the published data are not adequate to demonstrate 
the safety and effectiveness of the device.
3. Risks to Health
    a. Missed or delayed diagnosis--As a result of the questionable 
device performance of breast transilluminators, missed or delayed 
diagnosis are the most catastrophic risks to health for a woman. These 
devices depend on the users' visual interpretation of their own breast 
illumination. One scenario may result when a woman incorrectly 
interprets her transillumination as a tumor and suffers the ensuing 
anxiety from her belief that she has a cancer. Another scenario may 
result when a

[[Page 20274]]

woman incorrectly dismisses the findings of her transillumination and 
then suffers from a missed diagnosis or delayed diagnosis and delayed 
treatment. Ultimately, missed or delayed diagnoses could result in the 
need for more aggressive treatment and a potentially higher risk of 
death.
    b. Electrical shock--If a breast transilluminator is not designed 
properly, the user may receive an electrical shock.
    c. Optical radiation--Prolonged gazing directly into the light of a 
breast illuminator while engaged in ``bright light mode'' may result in 
retinal damage.

V. PMA Requirements

    A PMA for sorbent hemoperfusion devices for the treatment of 
hepatic coma and metabolic disturbances; cranial electrotherapy 
stimulator for the treatment of depression, anxiety, or insomnia; and 
transilluminator for breast evaluation 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) (21 CFR 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.'' (see Sec.  860.7(c)(2)).

VI. Opportunity To Request a Change in Classification

    Before requiring the filing of a PMA 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 sorbent 
hemoperfusion devices for the treatment of hepatic coma and metabolic 
disturbances; cranial electrotherapy stimulator for the treatment of 
depression, anxiety, and insomnia; and transilluminator for breast 
evaluation 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.
    Requests for reclassification submitted in response to the proposed 
rules will be considered under this proposed administrative order and 
do not need to be resubmitted. FDA continues to review the merits of 
the previous requests for reclassification submitted in response to the 
proposed rules and any preliminary decisions on those requests are not 
reflected in this proposed administrative order proposing to require 
the filing of a PMA for sorbent hemoperfusion devices for the treatment 
of hepatic coma and metabolic disturbances; cranial electrotherapy 
stimulator for the treatment of depression, anxiety, and insomnia; and 
transilluminator for breast evaluation.

VII. Proposed Reclassification

    FDA is proposing that sorbent hemoperfusion systems intended for 
the treatment of poisoning and drug overdose be reclassified from class 
III to class II. FDA is also proposing to create a separate 
classification for these devices to differentiate them from sorbent 
hemoperfusion systems for the treatment of hepatic coma and metabolic 
disturbances. FDA believes sorbent hemoperfusion devices for the 
treatment of poisoning and drug overdose can be useful in the treatment 
of emergent poisoning and drug overdose events by reducing the level of 
related toxic substances in the bloodstream, thereby reducing or 
preventing damage to the liver and resultant negative patient outcomes.
    FDA has considered sorbent hemoperfusion systems intended for the 
treatment of poisoning and drug overdose in accordance with the 
reserved criteria and determined that these devices require premarket 
notification. The Agency does not intend to exempt this proposed class 
II device from premarket notification (510(k)) submission as provided 
for under section 510(m) of the FD&C Act.

VIII. Summary of Reasons for Reclassification

    FDA believes that sorbent hemoperfusion systems intended for the 
treatment of poisoning and drug overdose should be reclassified into 
class II because special controls, in addition to general controls, are 
necessary to provide reasonable assurance of the safety and 
effectiveness of the device. In addition, there is now sufficient 
information to establish special controls to provide such assurance.

IX. Summary of Data Upon Which the Reclassification is Based

    FDA believes that the identified special controls, in addition to 
general controls, are necessary to provide reasonable assurance of 
safety and effectiveness. Therefore, in accordance with sections 513(e) 
and 515(i) of the FD&C Act and 21 CFR 860.130, based on new information 
with respect to the device, FDA, on its own initiative, is proposing to 
reclassify this preamendments class III device intended for the 
treatment of poisoning and drug overdose into class II. The Agency has 
identified special controls that would provide reasonable assurance of 
their safety and effectiveness. Sorbent hemoperfusion systems intended 
for the treatment of poisoning and drug overdose are prescription 
devices restricted to patient use only upon the authorization of a 
practitioner licensed by law to administer or use the device. (Proposed 
Sec.  876.5870(a); see section 520(e) of the FD&C Act and 21 CFR 
801.109 (Prescription devices)). Prescription-use restrictions are a 
type of general controls authorized under section 520(e) and defined as 
a general control in section 513(a)(1)(A)(i) of the FD&C Act.
    Sorbent hemoperfusion is used in a small number of poisoning and 
drug overdose cases each year. Due to the emergent nature of poisoning 
and drug overdose events, it is expected that the published clinical 
literature is limited and that randomized, controlled, clinical trials 
are not practical to conduct. Since the time of the original 
Gastroenterology-Urology Device Classification Panel recommendation in 
1981, sufficient new evidence has been developed to support a 
reclassification

[[Page 20275]]

of sorbent hemoperfusion system to class II with special controls for 
the treatment of poisoning and hepatic coma. There is valid scientific 
evidence which demonstrate that these devices are of clinical value in 
treating poisoning and drug overdose patients (Refs. 4 to 11). In this 
patient population, which is often relatively healthy prior to the 
poisoning or overdose event, quick removal of the poison or drug can 
greatly impact clinical outcomes, whereas in the hepatic coma and 
encephalopathy population, which typically exhibit severe underlying 
disease, comorbidities, and high mortality there is no substantive 
evidence on what substances need to be removed or decreased to bring on 
patient improvements or change clinical outcomes.
    Unlike sorbent hemoperfusion devices for the treatment of hepatic 
coma and metabolic disturbances, appropriate bench testing 
methodologies have also been developed to provide assurance that the 
device can remove a particular poison or drug from the bloodstream. FDA 
has developed sufficient confidence in these bench tests via review of 
510(k) submissions for these devices. In addition, a review of the 
available literature, FDA's MAUDE adverse event reporting database, and 
the manufacturer's submission to the 515(i) docket (74 FR 16214, April 
9, 2009) did not present evidence of significant reports of adverse 
events associated with the use of the sorbent hemoperfusion despite the 
longstanding use of these devices.
    Given the low occurrence of adverse events, the valid scientific 
evidence to support sorbent hemoperfusion for this use, and FDA's 
review experience with these devices, FDA believes that the identified 
special controls, including performance testing to ensure that the 
device is effective in removing particular poisons or drugs and is 
adequately designed and includes adequate safeguards, and labeling to 
inform users of inappropriate use conditions, in addition to general 
controls, provide reasonable assurance of effectiveness for this device 
for the treatment of poisoning and drug overdose.

X. Environmental Impact

    The Agency has determined under 21 CFR 25.30(h) and 25.34(b) that 
this action is of a type that does not individually or cumulatively 
have a significant effect on the human environment. Therefore, neither 
an environmental assessment nor an environmental impact statement is 
required.

XI. Paperwork Reduction Act of 1995

    This proposed order refers to collections of information that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).
    The collections of information in 21 CFR part 814 have been 
approved under OMB control number 0910-0231. The collections of 
information in 21 CFR part 807, subpart E, have been approved under OMB 
control number 0910-0120. The effect of this order, if finalized, is to 
shift certain devices from the 510(k) premarket notification process to 
the PMA process. To account for this change, FDA intends to transfer 
some of the burden from OMB control number 0910-0120, which is the 
control number for the 510(k) premarket notification process, to OMB 
control number 0910-0231, which is the control number for the PMA 
process. FDA estimates that it will receive 16 new PMAs as a result of 
this order, if finalized. Based on FDA's most recent estimates, this 
will result in a 4,842 hour burden increase. FDA also estimates that 
there will be 14 fewer 510(k) submissions as a result of this order, if 
finalized, because two manufacturers have not introduced their device 
to market yet. Based on FDA's most recent estimates, this will result 
in a 726 hour burden decrease. Therefore, on net, FDA expects a burden 
hour increase of 4,116 due to this proposed regulatory change.
    The collections of information in part 812 have been approved under 
OMB control number 0910-0078.

XII. 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) 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. 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 revoke the requirements in 21 CFR 
876.5870 related to the classification of sorbent hemoperfusion devices 
for the treatment of poisoning and drug overdose as class III devices 
and to codify the reclassification of sorbent hemoperfusion devices for 
the treatment of poisoning and drug overdose into class II.

XIII. Proposed Effective Date

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

XIV. Comments

    Comments submitted to the previous dockets for the relevant devices 
(cranial electrotherapy stimulator for the treatment of depression, 
anxiety, and insomnia FDA-2011-N-0504; transilluminator for breast 
evaluation FDA-2010-N-0412; sorbent hemoperfusion devices to treat 
hepatic coma and metabolic disturbances; and sorbent hemoperfusion 
devices for the treatment FDA-2012-M-0076) have been officially noted 
and do not need to be resubmitted. FDA will consider previous docket 
comments in issuing any final orders for these devices. Interested 
persons may submit either written comments regarding this document to 
the Division of Dockets Management (see ADDRESSES) or electronic 
comments to https://www.regulations.gov. It is only necessary to send 
one set of comments. Identify comments with the docket number found in 
brackets in the heading of this document. Received comments may be seen 
in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday, and will be posted to the docket at https://www.regulations.gov.

XV. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES), and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at https://www.regulations.gov. (FDA 
has verified the Web site addresses, but we are not responsible for any 
subsequent changes to the Web sites after this document publishes in 
the Federal Register.)

1. FDA Executive Summary prepared for the February 10, 2012, meeting 
of the Neurologic Devices Panel--Petitions to Request Change in 
Classification for Cranial Electrotherapy Stimulators.
2. Transcript, Center for Devices and Radiological Health Medical 
Devices Advisory Committee, Neurological

[[Page 20276]]

Devices Panel, February 10, 2012, 8 a.m., Hilton Washington DC 
North, 620 Perry Pkwy., Gaithersburg, MD. Available at https://www.fda.gov/AdvisoryCommittees/Calendar/ucm279941.htm.
3. Transcript, Center for Devices and Radiological Health Medical 
Devices Advisory Committee, Radiological Devices Panel, April 12, 
2012, 8 a.m., Hilton Washington DC North, 620 Perry Pkwy., 
Gaithersburg, MD. Available at https://www.fda.gov/AdvisoryCommittees/Calendar/ucm293275.htm.
4. Evenepoel, P., et al., ``Detoxifying Capacity and Kinetics of the 
Molecular Adsorbent Recycling System, Contribution of the Different 
Inbuilt Filters.'' Blood Purification, 21(3): p. 244-52, 2003.
5. Ash, S. R., et al., ``Treatment of Acetaminophen-Induced 
Hepatitis and Fulminant Hepatic Failure With Extracorporeal Sorbent-
Based Devices,'' Advances in Renal Replacement Therapy, 9(1): p. 42-
53, 2002.
6. Akdogan, M., et al., ``Experience With Liver Dialysis in 
Acetaminophen Induced Fulminant Hepatic Failure: A Preliminary 
Report,'' Turkish Journal of Gastroenterology, 14(3): p. 164-7, 
2003.
7. Ash, S. R., et al., ``Treatment of Severe Tricyclic 
Antidepressant Overdose With Extracorporeal Sorbent 
Detoxification.'' Advances in Renal Replacement Therapy, 9(1): p. 
31-41, 2002.
8. De Schoenmakere, G., et al., ``Phenytoin Intoxication in 
Critically Ill Patients,'' American Journal of Kidney Diseases, 
45(1): p. 189-92, 2005.
9. Covic, A., et al., ``Successful Use of Molecular Absorbent 
Regenerating System (MARS) Dialysis for the Treatment of Fulminant 
Hepatic Failure in Children Accidentally Poisoned by Toxic Mushroom 
Ingestion,'' Liver International, 23 Suppl 3: p. 21-7, 2003.
10. Shi, Y., et al., ``MARS: Optimistic Therapy Method in Fulminant 
Hepatic Failure Secondary to Cytotoxic Mushroom Poisoning--A Case 
Report,'' Liver, 22 Suppl 2: p. 78-80, 2002.
11. Wu, B .F. and M. M. Wang, Molecular Adsorbent Recirculating 
System In Dealing With Maternal Amanita Poisoning During the Second 
Pregnancy Trimester: A Case Report, Hepatobiliary and Pancreatic 
Diseases International, 3(1): p. 152-4, 2004.

List of Subjects

21 CFR Part 876

    Medical devices.

21 CFR Part 882

    Medical devices, Neurological devices.

21 CFR Part 892

    Medical devices, Radiation protection, X-rays.

    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 parts 876, 882, and 892 be amended as follows:

PART 876--GASTROENTEROLOGY-UROLOGY DEVICES

0
1. The authority citation for 21 CFR part 876 continues to read as 
follows:

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

0
2. Section 876.5870 is revised to read as follows:


Sec.  876.5870  Sorbent hemoperfusion system.

    (a) Identification. A sorbent hemoperfusion system is a 
prescription device that consists of an extracorporeal blood system 
similar to that identified in the hemodialysis system and accessories 
(Sec.  876.5820) and a container filled with adsorbent material that 
removes a wide range of substances, both toxic and normal, from blood 
flowing through it. The adsorbent materials are usually activated-
carbon or resins which may be coated or immobilized to prevent fine 
particles entering the patient's blood. The generic type of device may 
include lines and filters specifically designed to connect the device 
to the extracorporeal blood system. The device is used in the treatment 
of poisoning, drug overdose, hepatic coma, or metabolic disturbances.
    (b) Classification. (1) Class II (special controls) when the device 
is intended for the treatment of poisoning and drug overdose. The 
special controls for this device are:
    (i) The device must be demonstrated to be biocompatible;
    (ii) Performance data to demonstrate the mechanical integrity of 
the device (e.g., tensile, flexural, and structural strength), 
including testing for the possibility of leaks, ruptures, release of 
particles, and/or disconnections;
    (iii) Performance data to demonstrate device sterility and shelf 
life;
    (iv) Bench performance data to demonstrate device functionality in 
terms of substances, toxins, and drugs removed by the device, and the 
extent that these are removed when the device is used according to its 
labeling, and to validate the device's safeguards;
    (v) Summary of clinical experience with the device that discusses 
and analyzes device safety and performance, including a list of adverse 
events observed during the testing;
    (vi) Labeling controls, including appropriate warnings, 
precautions, cautions, and contraindications statements to alert and 
inform users of proper device use and potential clinical adverse 
effects, including blood loss, platelet loss, leukopenia, hemolysis, 
hypotension, clotting, metabolic disturbances, and loss of vital 
nutrients and substances; labeling recommendations must be consistent 
with the performance data obtained for the device, and must include a 
list of the drugs and/or poisons the device has been demonstrated to 
remove, and the extent for removal/depletion; and
    (vii) For those devices that incorporate electrical components, 
appropriate analysis and testing to validate electrical safety and 
electromagnetic compatibility.
    (2) Class III (premarket approval) when the device is intended for 
the treatment of hepatic coma and metabolic disturbances.
    (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 FDA by [DATE 
90 DAYS AFTER DATE OF PUBLICATION OF THE FINAL ORDER IN THE FEDERAL 
REGISTER], for any sorbent hemoperfusion system indicated for treatment 
of hepatic coma or metabolic disturbances that was in commercial 
distribution before May 28, 1976, or that has, by [DATE 90 DAYS AFTER 
DATE OF PUBLICATION OF THE FINAL ORDER IN THE FEDERAL REGISTER], been 
found to be substantially equivalent to any sorbent hemoperfusion 
device indicated for treatment of hepatic coma or metabolic 
disturbances that was in commercial distribution before May 28, 1976. 
Any other sorbent hemoperfusion system device indicated for treatment 
of hepatic coma or metabolic disturbances shall have an approved PMA or 
declared completed PDP in effect before being placed in commercial 
distribution.

PART 882--NEUROLOGICAL DEVICES

0
3. 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
4. Section 882.5800 is amended by revising paragraph (c) to read as 
follows:


Sec.  882.5800  Cranial electrotherapy stimulator.

* * * * *
    (c) Date PMA or notice of completion of PDP is required. A PMA or 
notice of completion of a PDP is required to be filed with the Food and 
Drug Administration by [A DATE WILL BE ADDED 90 DAYS AFTER DATE OF 
PUBLICATION OF A FUTURE FINAL ORDER IN THE FEDERAL REGISTER],

[[Page 20277]]

for any cranial electrotherapy stimulator device that was in commercial 
distribution before May 28, 1976, or that has, by [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 
cranial electrotherapy stimulator device that was in commercial 
distribution before May 28, 1976. Any other cranial electrotherapy 
stimulator device shall have an approved PMA or declared completed PDP 
in effect before being placed in commercial distribution.

PART 892--RADIOLOGY DEVICES

0
5. The authority citation for 21 CFR part 892 continues to read as 
follows:

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

0
6. Section 892.1990 is amended by revising paragraph (c) to read as 
follows:


Sec.  892.1990  Transilluminator for breast evaluation.

* * * * *
    (c) Date PMA or notice of completion of PDP is required. A PMA or 
notice of completion of a PDP is required to be filed with the Food and 
Drug Administration by [A DATE WILL BE ADDED 90 DAYS AFTER DATE OF 
PUBLICATION OF A FUTURE FINAL ORDER IN THE FEDERAL REGISTER], for any 
transilluminator for breast evaluation that was in commercial 
distribution before May 28, 1976, or that has, by [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 
transilluminator for breast evaluation that was in commercial 
distribution before May 28, 1976. Any other transilluminator for breast 
evaluation shall have an approved PMA or declared completed PDP in 
effect before being placed in commercial distribution.

    Dated: March 29, 2013.
Peter Lurie,
Acting Associate Commissioner for Policy and Planning.
[FR Doc. 2013-07730 Filed 4-3-13; 8:45 am]
BILLING CODE 4160-01-P