
[Federal Register Volume 78, Number 98 (Tuesday, May 21, 2013)]
[Proposed Rules]
[Pages 29672-29680]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-12122]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 870

[Docket No. FDA-2013-N-0487]


Cardiovascular Devices; Reclassification of External Counter-
Pulsating Devices for Treatment of Chronic Stable Angina; Effective 
Date of Requirement for Premarket Approval for External Counter-
Pulsating Devices for Other 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 external counter-pulsating (ECP) 
devices for treatment of chronic stable angina that is refractory to 
optimal anti-anginal medical therapy and without options for 
revascularization, 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 ECP 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

[[Page 29673]]

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 August 19, 2013. FDA intends that, if a final order based on 
this proposed order is issued, anyone who wishes to continue to market 
ECP devices for specified intended uses listed in section IX 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 XVII for the proposed 
effective date of any final order based on this proposed order.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-0487, by any of the following methods:

Electronic Submissions

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

Written Submissions

    Submit written submissions in the following ways:
     Mail/Hand delivery/Courier (for paper 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 No. FDA-2013-N-0487 for this rulemaking. All comments 
received may be posted without change to http://www.regulations.gov, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section.
    Docket: For access to the docket to read background documents or 
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: Angela Krueger, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 1666, Silver Spring, MD 20993, 301-796-6380, 
angela.krueger@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended 
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L. 
94-295), the Safe Medical Devices Act of 1990 (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 
(Public Law 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).
    Under section 513 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 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 (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.

A. Reclassification

    FDA is publishing this document to propose the reclassification of 
ECP devices for treatment of chronic stable angina that is refractory 
to optimal anti-anginal medical therapy and without options for 
revascularization 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

[[Page 29674]]

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, 388-391 (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 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 
Association v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 
1062 (1985).)
    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, 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 can include information 
from clinical and preclinical tests or studies that demonstrate the 
safety or effectiveness of the device but does not include descriptions 
of methods of manufacture or product composition and other trade 
secrets.
    Section 513(e)(1) of the FD&C Act sets forth the process for 
issuing a final order. 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 external-counter pulsating devices, and 
therefore, has met this requirement under section 515(b)(1) of the FD&C 
Act.
    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.

B. Requirement for Premarket Approval Application

    FDA is proposing to require PMAs for ECP devices for Certain 
Specified Intended Uses.\1\
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    \1\ For the purposes of this proposed order, the term ``Certain 
Specified Intended Uses'' includes the following intended uses:
     Unstable angina pectoris;
     Acute myocardial infarction;
     Cardiogenic shock;
     Congestive heart failure;
     Postoperative treatment of patients who have undergone 
coronary artery bypass surgery;
     Peripheral arterial disease associated with the 
following: Ischemic ulcers rest pain or claudication; threatened 
gangrene; insufficient blood supply at an amputation site; 
persisting ischemia after embolectomy or bypass surgery; and/or pre- 
and post-arterial reconstruction to improve runoff;
     Diabetes complicated by peripheral arterial disease or 
other conditions possibly related to arterial insufficiency 
including the following: Nocturnal leg cramps and/or necrobiosis 
diabeticorum;
     Venous diseases, including the following: Prophylaxis 
of deep vein thrombophlebitis; edema (e.g., chronic lymphedema) and/
or induration (e.g., stasis dermatitis) associated with chronic 
venous stasis; venous stasis ulcers; and/or thrombophlebitis;
     Athletic injuries, including the following: Charley 
horses, pulled muscles, and/or edematous muscles; and
     Necrotizing cellulitis.
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    Section 515(b)(1) of the FD&C Act sets forth the process for 
issuing a final order. 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 external-
counter pulsating 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)
    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 ECP 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 1980, the 30-month period has 
expired (45 FR 7966; February 5, 1980). Therefore, if the proposal to 
require premarket approval for ECP 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

[[Page 29675]]

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 ECP devices for Certain Specified Intended Uses.

II. Regulatory History of the Device

    In the preamble to the proposed rule (44 FR 13426, March 9, 1979), 
the Cardiovascular Device Classification Panel (the 1979 Panel) 
recommended that ECP devices be classified into class III because the 
device is life-supporting and is potentially hazardous to life or 
health even when properly used. The 1979 Panel noted that the device 
surrounds the limbs to which it is attached, is in direct contact with 
the skin, and is used in a clinical environment where excessive leakage 
current can be a serious hazard. As a result the electrical 
characteristics of this device need to meet certain requirements. The 
1979 Panel further noted that the performance characteristics, 
including accuracy, reproducibility, and any limitations on the 
device's cardiac synchronization and pressure application should be 
maintained at a generally accepted satisfactory level and should be 
made known to the user through special labeling. In addition, the 
device is used with other devices in a system that may be hazardous if 
not satisfactorily assembled, used, and maintained. The 1979 Panel 
indicated that general controls alone would not provide sufficient 
control over the performance characteristics of the device, and that 
there was not sufficient information to establish a performance 
standard to provide assurance of the safety and effectiveness of the 
device. Consequently, the 1979 Panel believed that premarket approval 
was necessary to assure the safety and effectiveness of the device. In 
1980, FDA classified external counter-pulsating devices into class III 
after receiving no comments on the proposed rule (45 FR 7966, February 
5, 1980).
    In 1987, FDA published a clarification by codifying a statement 
that no effective date had been established for the requirement for 
premarket approval for external counter-pulsating devices (52 FR 17732 
at 17737, May 11, 1987).
    In 2009, FDA published an order for the submission of information 
on external counter-pulsating devices by August 7, 2009 (74 FR 16214, 
April 9, 2009). FDA received five responses to that order from device 
manufacturers recommending that ECP devices be reclassified to class 
II. The manufacturers stated that safety and effectiveness of these 
devices may be assured by device design, performance testing, and 
labeling (special controls).
    As explained further in sections VII and XI, a meeting of the 
Circulatory System Devices Panel (the 2012 Panel) took place December 
5, 2012, to discuss whether ECP devices should be reclassified or 
remain in class III. The 2012 Panel recommended that ECP devices 
intended for treatment of chronic stable angina that is refractory to 
optimal anti-anginal medical therapy and without options for 
revascularization be reclassified to class II with special controls and 
ECP devices for Certain Specified Intended Uses remain in class III. 
Because the safety and effectiveness of ECP devices for Certain 
Specified Intended Uses has not been established through adequate 
scientific evidence, the device presents a potential unreasonable risk 
of injury given that the benefit of ECP devices for these uses is 
unknown. In addition, there was insufficient information to establish 
special controls for these uses. FDA is not aware of new information 
that would provide a basis for a different recommendation or findings.

III. Device Description

    An external counter-pulsating device is a noninvasive device used 
to assist the heart by applying positive or negative pressure to one or 
more of the body's limbs in synchrony with the heart cycle. An ECP 
system typically consists of a treatment table, a set of pressure 
cuffs, and a control console. The control console controls a pneumatic 
circuit that inflates and deflates the pressure cuffs. The inflatable 
pressure cuffs are wrapped around the calves, the lower and upper 
thighs, and/or the buttocks. They are rapidly and sequentially 
inflated, starting from the calves and moving proximally during the 
diastolic phase of a cardiac cycle. This creates an arterial retrograde 
flow of blood towards the heart and increases blood flow to the 
coronary arteries at a time when resistance to the coronary blood flow 
is low. The inflation of the cuffs also simultaneously increases the 
volume of venous blood returned to the right side of the heart, 
providing greater filling of the ventricle for ejection. The 
synchronization between the cardiac cycle and the inflation/deflation 
cycle of the cuffs is coordinated by custom software contained within 
the control console that monitors and interprets the patient's 
electrocardiogram and heart rhythm.

IV. Proposed Reclassification

    FDA is proposing that ECP devices for treatment of chronic stable 
angina that is refractory to optimal anti-anginal medical therapy and 
without options for revascularization 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 their 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 and Sec.  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 for the treatment of 
chronic stable angina that is refractory to optimal anti-anginal 
medical therapy and without options for revascularization. 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 ECP devices for treatment of chronic 
stable angina that

[[Page 29676]]

is refractory to optimal anti-anginal medical therapy and without 
options for revascularization.
    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 ECP devices for treatment of chronic stable angina that 
is refractory to optimal anti-anginal medical therapy and without 
options for revascularization in accordance with the reserved criteria 
set forth in section 513(a) of the FD&C Act and decided that the device 
does require premarket notification. Therefore, the Agency does not 
intend to exempt this proposed class II device from premarket 
notification (510(k)) submission.

V. Risks to Health

    After considering available information, including the 
recommendations of the advisory committees (panels) for the 
classification of these devices, FDA has evaluated the risks to health 
associated with the use of ECP devices and determined that the 
following risks to health are associated with its use:
     Cardiac arrhythmias--Excessive electrical leakage current 
may disturb the normal electrophysiology of the heart, leading to the 
onset of cardiac arrhythmias.
     Trauma/Irritation to the limb--Improper mechanical design, 
including selection of materials, may cause bruising, blistering, 
muscle aches, and/or pain to the limb(s).
     Ineffective cardiac assistance--Improper timing or failure 
to synchronize the device with the appropriate phase of the cardiac 
cycle may lead to ineffective cardiac assistance by the device.

VI. Summary of Reasons for Reclassification

    If properly manufactured and used, ECP devices can provide a 
treatment option for patients with chronic stable angina that is 
refractory to optimal anti-anginal medical therapy and without options 
for revascularization, especially patients who are not candidates for 
treatment by revascularization and who are refractory to medical 
therapy, by increasing blood flow to the coronary arteries and 
increasing the volume of venous blood returned to the right side of the 
heart, providing greater filling of the ventricle for ejection. FDA 
believes that ECP devices intended for treatment of chronic stable 
angina that is refractory to optimal anti-anginal medical therapy and 
without options for revascularization should be reclassified from class 
III to class II because special controls, in addition to general 
controls, can be established to provide reasonable assurance of the 
safety and effectiveness of the device, and because general controls 
themselves are insufficient to provide reasonable assurance of its 
safety and effectiveness. In addition, there is now adequate 
effectiveness information sufficient to establish special controls to 
provide such assurance.

VII. Summary of Data Upon Which the Reclassification Is Based

    Since the time of the 1979 Panel recommendation, sufficient 
evidence has been developed to support a reclassification of ECP 
devices to class II with special controls for the treatment of chronic 
stable angina that is refractory to optimal anti-anginal medical 
therapy and without options for revascularization. FDA has been 
reviewing these devices for many years and their risks are well known. 
FDA conducted a comprehensive review of available literature for ECP 
devices for treatment of chronic stable angina. FDA's review found 4 
randomized controlled trials (Refs. 1 to 4), 21 observational studies, 
and a meta-analysis of 13 individual studies that provided consistent 
evidence of the effectiveness of ECP devices for the treatment of 
chronic stable angina that is refractory to optimal anti-anginal 
medical therapy and without options for revascularization. Although all 
of the studies of ECP for the treatment of angina considered 
individually have various limitations, the consistency of the study 
results, the wide range of angina-related endpoints involved in the 
studies, the large magnitude of the demonstrated beneficial outcomes, 
the long duration (up to 3 years) of some of the beneficial outcomes, 
and the fact that many or most of the subjects had a disease that was 
refractory to the effects of any other treatment, all support a 
conclusion of reasonable evidence for the effectiveness of ECP in the 
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization. The 
safety profile of ECP devices has been established based on the few 
relevant adverse events reported in the literature or through FDA's 
Manufacturer and User Facility Device Experience (MAUDE) database. In 
addition, bench studies designed to demonstrate the devices' ability to 
function as intended have been well characterized.
    The 2012 Panel discussed and made recommendations regarding the 
regulatory classification of ECP devices to either reconfirm to class 
III (subject to premarket approval application) or reclassify to class 
II (subject to special controls) as directed by section 515(i) of the 
FD&C Act.
    FDA's presentation to the 2012 Panel included a summary of the 
available safety and effectiveness information for ECP devices for 
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization, 
including adverse event reports from the MAUDE database and available 
literature. Based on the available scientific literature that supports 
that ECP may be beneficial for patients with chronic stable angina who 
are not revascularization candidates and who are refractory to optimal 
medical therapy, FDA recommended to the 2012 Panel that ECP devices for 
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization be 
reclassified to class II (special controls). The 2012 Panel agreed with 
FDA's conclusion that the available scientific evidence is adequate to 
support the safety and effectiveness of ECP devices for treatment of 
chronic stable angina that is refractory to optimal anti-anginal 
medical therapy and without options for revascularization.
    The 2012 Panel also agreed with the identified risks to health 
outlined in section V. FDA recommended that a fourth risk to health, 
failure to identify the correct patient population, be considered in 
the 2012 Panel's deliberations. FDA proposed this risk to health to 
capture situations in which the device was used properly but patients 
experienced adverse events associated with their underlying 
comorbidities. For example, based on FDA's evaluation of Medical Device 
Reporting Regulations more than half were associated with patients with 
congestive heart failure who experience exacerbation of the condition 
following use of the device. However, the 2012 Panel questioned whether 
failure to identify the correct patient population was really a risk to 
health and noted that the risk is vague and too broad. FDA agreed with 
the 2012 Panel's recommendation and removed the proposed fourth risk. 
The 2012 Panel agreed with FDA's proposed special controls outlined in 
section VIII. In addition, the 2012 Panel also agreed with FDA that ECP 
devices are not considered to be life-supporting. This differs from the 
1979 Panel's recommendation outlined in the proposed rule for this 
device type (44 FR 13426, March 9, 1979). The 2012 Panel transcript and 
other meeting

[[Page 29677]]

materials are available on FDA's Web site (Ref. 5).

VIII. Proposed Special Controls

    FDA believes that the following special controls, together with 
general controls, are sufficient to mitigate the risks to health 
described in section V:
    (1) Nonclinical performance evaluation of the device must 
demonstrate a reasonable assurance of safety and effectiveness for 
applied pressure, synchronization of therapy with the appropriate phase 
of the cardiac cycle, and functionality of alarms during a device 
malfunction or an abnormal patient condition;
    (2) Reliabilities of the mechanical and electrical systems must be 
established through bench testing under simulated use conditions and 
matched by appropriate maintenance schedules;
    (3) Software design and verification and validation must be 
appropriately documented;
    (4) The skin-contacting components of the device must be 
demonstrated to be biocompatible;
    (5) Appropriate analysis and testing must be conducted to verify 
electrical safety and electromagnetic compatibility of the device; and
    (6) Labeling must bear all information required for the safe and 
effective use of the device, including a detailed summary of the 
device-related and procedure-related complications pertinent to use of 
the device.
    ECP devices 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.  870.5225(a) (21 CFR 870.5225(a)); 
see section 520(e) of the FD&C Act and 21 CFR 801.109 (Prescription 
devices)). Prescription-use requirements are a type of general control 
authorized under section 520(e) of the FD&C Act and defined as a 
general control in section 513(a)(1)(A)(i) of the FD&C Act; and under 
Sec.  807.81, the device would continue to be subject to 510(k) 
notification requirements.

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 ECP devices 
intended for the following uses (Certain Specified Intended Uses):
     Unstable angina pectoris;
     Acute myocardial infarction;
     Cardiogenic shock;
     Congestive heart failure;
     Postoperative treatment of patients who have undergone 
coronary artery bypass surgery;
     Peripheral arterial disease associated with the following: 
Ischemic ulcers rest pain or claudication, threatened gangrene, 
insufficient blood supply at an amputation site, persisting ischemia 
after embolectomy or bypass surgery, and/or pre and post-arterial 
reconstruction to improve runoff;
     Diabetes complicated by peripheral arterial disease or 
other conditions possibly related to arterial insufficiency including 
the following: Nocturnal leg cramps and/or necrobiosis diabeticorum;
     Venous diseases, including the following: Prophylaxis of 
deep vein thrombophlebitis, edema (e.g., chronic lymphedema) and/or 
induration (e.g., stasis dermatitis) associated with chronic venous 
stasis, venous stasis ulcers, and/or thrombophlebitis;
     Athletic injuries, including the following: Charley 
horses, pulled muscles, and/or edematous muscles; and
     Necrotizing cellulitis.
    An applicant whose device was legally in commercial distribution 
before May 28, 1976, or whose device has been found to be substantially 
equivalent to such a device, will be permitted to continue marketing 
such class III devices during FDA's review of the PMA provided that the 
PMA is timely filed. FDA intends to review any PMA for the device 
within 180 days of the date of filing. FDA cautions that under section 
515(d)(1)(B)(i) of the FD&C Act, the Agency may not enter into an 
agreement to extend the review period for a PMA beyond 180 days unless 
the Agency finds that ``the continued availability of the device is 
necessary for the public health.''
    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, who does not intend to market such device 
for any one or more Certain Specified Intended Uses, may remove such 
intended uses from the device's labeling by initiating a correction 
within 90 days after issuance of any final order based on this 
proposal. 21 CFR 806.10(a)(2) requires a device manufacturer or 
importer initiating a correction to remedy a violation of the FD&C Act 
that may present a risk to health to submit a written report of the 
correction to FDA.
    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 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 ECP devices intended for the treatment of chronic stable 
angina that is refractory to optimal anti-Anginal medical therapy and 
without options for revascularization 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 require a new premarket submission for ECP devices 
intended for the treatment of chronic stable angina that is refractory 
to optimal anti-anginal medical therapy and without options for 
revascularization.

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 for Certain Specified Intended Uses and (2) 
the benefits to the public from the use of ECP devices for Certain 
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, April 9, 2009) and any additional information that FDA has 
obtained. Additional information regarding the risks as well as 
classification associated with this

[[Page 29678]]

device type can be found in 44 FR 13426, 45 FR 7966, and 52 FR 17732 at 
17737.

XI. Device Subject to the Proposal to Require a PMA--External Counter-
Pulsating Devices for Uses Other Than Treatment of Chronic Stable 
Angina That Is Refractory to Optimal Anti-Anginal Medical Therapy and 
Without Options for Revascularization (Sec.  870.5225(c))

A. Identification

    An external counter-pulsating device is a noninvasive, prescription 
device used to assist the heart by applying positive or negative 
pressure to one or more of the body's limbs in synchrony with the heart 
cycle.

B. Summary of Data

    For uses other than treatment of chronic stable angina that is 
refractory to optimal anti-anginal medical therapy and without options 
for revascularization as specified in section IX, FDA concludes that 
the safety and effectiveness of these devices have not been established 
by adequate scientific evidence. There is limited scientific evidence 
regarding the effectiveness of ECP devices for uses other than 
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization. 
Review of the published scientific literature revealed a lack of valid 
scientific evidence to support indications other than treatment of 
chronic stable angina that is refractory to optimal anti-anginal 
medical therapy and without options for revascularization. There were 
few studies that discussed other uses and those studies did not provide 
evidence of reasonable assurance of effectiveness due to lack of 
relevant details regarding study design, conduct and results, use of 
flawed study designs, and publication bias (Refs. 6 to 11). FDA 
presented the findings of our literature search for ECP devices for 
uses other than treatment of chronic stable angina that is refractory 
to optimal anti-anginal medical therapy and without options for 
revascularization to the Circulatory System Devices Panel (the Panel) 
on December 5, 2012. Based on FDA's findings, the Panel concluded that 
available scientific evidence is not adequate to support the 
effectiveness of ECP devices for uses other than treatment of chronic 
stable angina that is refractory to optimal anti-anginal medical 
therapy and without options for revascularization. The Panel also 
recommended that ECP devices for Certain Specified Intended Uses should 
remain in class III (subject to premarket approval application). 
Although the Panel noted that ECP devices are not life-supporting, the 
devices present a potential unreasonable risk of injury given that 
risks to health exist that are not balanced by a benefit that has been 
established through adequate scientific evidence to demonstrate safety 
and effectiveness.
    The Panel transcript and other meeting materials are available on 
FDA's Web site (Ref. 5).

C. Risks to Health

    The risks to health for ECP devices for uses other than treatment 
of chronic stable angina that is refractory to optimal anti-anginal 
medical therapy and without options for revascularization are the same 
as outlined in section V.

D. Benefits of ECP Devices

    As discussed previously, there is limited scientific evidence 
regarding the effectiveness of ECP devices for uses other than 
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization. 
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, claims for the devices state that the devices have 
the potential to benefit the public by augmenting cardiac output, 
increasing coronary blood flow, and stimulating circulation in the 
lower extremities.

XII. PMA Requirements

    A PMA for ECP devices for 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.'' (See Sec.  
860.7(c)(2).)

XIII. 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 ECP devices for 
Certain Specified Intended Uses is to be in the form of a 
reclassification petition containing the information required by Sec.  
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) 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 Sec.  
870.5225 related to the classification of external counter-pulsating 
devices for chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization as 
class III

[[Page 29679]]

devices and to codify the reclassification of external counter-
pulsating devices for chronic stable angina that is refractory to 
optimal anti-anginal medical therapy and without options for 
revascularization into class II.

XV. Environmental Impact

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

XVI. 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 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. FDA 
estimates that there will be two fewer 510(k) submissions as a result 
of this order, if finalized. Based on FDA's most recent estimates, this 
will result in a 91-hour burden decrease to OMB control number 0910-
0120, which is the control number for the 510(k) premarket notification 
process. However, because FDA does not expect to receive any new PMAs 
as a result of this order, we estimate no burden increase to OMB 
control number 0910-0231 based on this order, if finalized. Therefore, 
on net, FDA expects a burden hour decrease of 91 due to this proposed 
regulatory change.
    The collections of information in part 812 have been approved under 
OMB control number 0910-0078.

XVII. 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.

XVIII. Comments

    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). It is only necessary to 
submit one set of comments. Identify comments with the docket number 
found in the 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 http://www.regulations.gov.

XIX. 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 http://www.regulations.gov. (FDA 
has verified the Web site address in this reference section, but FDA is 
not responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register.)

1. Arora, R. R., T. M. Chou, D. Jain, et al., ``The Multicenter 
Study of Enhanced External Counterpulsation (MUST-EECP): Effect of 
EECP on Exercise-Induced Myocardial Ischemia and Anginal Episodes,'' 
Journal of the American College of Cardiology, vol. 33, pp. 1833-
1840, 1999.
2. Arora, R. R., T. M. Chou, D. Jain, et al., ``Effects of Enhanced 
External Counterpulsation on Health-Related Quality of Life Continue 
12 Months After Treatment: A Substudy of the Multicenter Study of 
Enhanced External Counterpulsation,'' Journal of Investigative 
Medicine, vol. 50, pp. 25-32, 2002.
3. Gloekler, S., P. Meier, S. F. de Marchi, et al., ``Coronary 
Collateral Growth by External Counterpulsation: A Randomised 
Controlled Trial,'' Heart, vol. 96, pp. 202-207, 2010.
4. Casey, D. P., D. T. Beck, W. W. Nichols, et al., ``Effects of 
Enhanced External Counterpulsation on Arterial Stiffness and 
Myocardial Oxygen Demand in Patients With Chronic Angina Pectoris,'' 
American Journal of Cardiology, vol. 107, pp. 1466-1472, 2011.
5. FDA, the Panel transcript and other meeting materials, (http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm300073.htm).
6. Abbottsmith, C. W., E. S. Chung, T. Varricchione, et al., 
``Enhanced External Counterpulsation Improves Exercise Duration and 
Peak Oxygen Consumption in Older Patients With Heart Failure: A 
Subgroup Analysis of the PEECH Trial,'' Congestive Heart Failure, 
vol. 12, pp. 307-311, 2006.
7. Feldman, A. M., M. A. Silver, G. S. Francis, et al., ``Enhanced 
External Counterpulsation Improves Exercise Tolerance in Patients 
With Chronic Heart Failure,'' Journal of the American College of 
Cardiology, vol. 48, pp. 1198-1205, 2006.
8. Kozdag, G., G. Ertas, F. Aygun, et al., ``Clinical Effects of 
Enhanced External Counterpulsation Treatment in Patients With 
Ischemic Heart Failure,'' Anadolu Kardiyol Derg, vol. 12, pp. 214-
221, 2012.
9. Triulzi, E., S. Devizzi, G. Rovelli, et al., [``Efficacy of 
Enhanced Aortic Diastolic Pressure With An External Counterpulsation 
Method in the Acute Myocardial Infarction'' (author's translation)], 
Giornale Italiano di Cardiologia, vol. 10, pp. 690-702, 1980.
10. Vijayaraghavan, K., L. Santora, J. Kahn, et al., ``New Graduated 
Pressure Regimen for External Counterpulsation Reduces Mortality and 
Improves Outcomes in Congestive Heart Failure: A Report From the 
Cardiomedics External Counterpulsation Patient Registry,'' 
Congestive Heart Failure, vol. 11, pp. 147-152, 2005.
11. Amsterdam, E. Z., J. Banas, J. M. Criley, et al., ``Clinical 
Assessment of External Pressure Circulatory Assistance in Acute 
Myocardial Infarction,'' American Journal of Cardiology, vol. 45, 
pp. 349-356, 1980.

List of Subjects in 21 CFR Part 870

    Medical devices, Cardiovascular 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 870 be amended as follows:

PART 870--CARDIOVASCULAR DEVICES

0
1. The authority citation for 21 CFR part 870 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Revise Sec.   870.5225 to read as follows:


Sec.  870.5225  External counter-pulsating device.

    (a) Identification. An external counter-pulsating device is a 
noninvasive, prescription device used to assist the heart by applying 
positive or negative pressure to one or more of the body's limbs in 
synchrony with the heart cycle.
    (b) Classification. (1) Class II (special controls) when the device 
is intended for the treatment of chronic stable angina that is 
refractory to optimal anti-anginal medical therapy and without options 
for revascularization. The special controls for this device are:
    (i) Nonclinical performance evaluation of the device must 
demonstrate a reasonable assurance of safety and effectiveness for 
applied pressure, synchronization of therapy with the appropriate phase 
of the cardiac cycle, and functionality of

[[Page 29680]]

alarms during a device malfunction or an abnormal patient condition;
    (ii) Reliabilities of the mechanical and electrical systems must be 
established through bench testing under simulated use conditions and 
matched by appropriate maintenance schedules;
    (iii) Software design and verification and validation must be 
appropriately documented;
    (iv) The skin-contacting components of the device must be 
demonstrated to be biocompatible;
    (v) Appropriate analysis and testing must be conducted to verify 
electrical safety and electromagnetic compatibility of the device; and
    (vi) Labeling must bear all information required for the safe and 
effective use of the device, including a detailed summary of the 
device-related and procedure-related complications pertinent to use of 
the device.
    (2) Class III (premarket approval) for the following intended uses: 
Unstable angina pectoris; acute myocardial infarction; cardiogenic 
shock; congestive heart failure; postoperative treatment of patients 
who have undergone coronary artery bypass surgery; peripheral arterial 
disease associated with ischemic ulcers rest pain or claudication, 
threatened gangrene, insufficient blood supply at an amputation site, 
persisting ischemia after embolectomy or bypass surgery, and/or pre- 
and post-arterial reconstruction to improve runoff; diabetes 
complicated by peripheral arterial disease or other conditions possibly 
related to arterial insufficiency including nocturnal leg cramps and/or 
necrobiosis diabeticorum; venous diseases, including prophylaxis of 
deep vein thrombophlebitis, edema (e.g., chronic lymphedema) and/or 
induration (e.g., stasis dermatitis) associated with chronic venous 
stasis, venous stasis ulcers, and/or thrombophlebitis; athletic 
injuries, including Charley horses, pulled muscles and/or edematous 
muscles; necrotizing cellulitis.
    (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 on or 
before [A DATE WILL BE ADDED THAT WILL BE 90 DAYS AFTER DATE OF 
PUBLICATION OF A FUTURE FINAL ORDER IN THE FEDERAL REGISTER], for any 
external counter-pulsating device, with an intended use described in 
(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 THAT WILL BE 
90 DAYS AFTER DATE OF PUBLICATION OF A FUTURE FINAL ORDER IN THE 
FEDERAL REGISTER], been found to be substantially equivalent to any 
external counter-pulsating device, with an intended use described in 
(b)(2) of this section, that was in commercial distribution before May 
28, 1976. Any other external counter-pulsating device with an intended 
use described in (b)(2) of this section shall have an approved PMA or 
declared completed PDP in effect before being placed in commercial 
distribution.

    Dated: May 15, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-12122 Filed 5-20-13; 8:45 am]
BILLING CODE 4160-01-P


