Cardiovascular Devices; Reclassification of Intra-Aortic Balloon and Control Systems (IABP) for Acute Coronary Syndrome, Cardiac and Non-Cardiac Surgery, or Complications of Heart Failure; Effective Date of Requirement for Premarket Approval for IABP for Other Specific Intended Uses, 36702-36711 [2013-14553]

Agencies

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

[Federal Register Volume 78, Number 118 (Wednesday, June 19, 2013)]
[Proposed Rules]
[Pages 36702-36711]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-14553]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 870

[Docket No. FDA-2013-N-0581]


Cardiovascular Devices; Reclassification of Intra-Aortic Balloon 
and Control Systems (IABP) for Acute Coronary Syndrome, Cardiac and 
Non-Cardiac Surgery, or Complications of Heart Failure; Effective Date 
of Requirement for Premarket Approval for IABP for Other Specific 
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 intra-aortic balloon and

[[Page 36703]]

control system devices when indicated for acute coronary syndrome, 
cardiac and non-cardiac surgery, or complications of heart failure, 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 intra-aortic balloon and control 
systems when indicated for septic shock or pulsatile flow generation. 
The Agency is also summarizing its proposed findings regarding the 
degree of risk of illness or injury designed to be eliminated or 
reduced by requiring the devices to meet the statute's approval 
requirements when indicated for septic shock or pulsatile flow 
generation. 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 by September 17, 
2013. FDA intends that, if a final order based on this proposed order 
is issued, anyone who wishes to continue to market intra-aortic balloon 
and control system devices indicated for septic shock or pulsatile flow 
generation 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 of this document 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-0581, 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 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-0581 for this rulemaking. 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.
    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: 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 
(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), establish 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 
amended section 513(e) of the FD&C Act, changing the process for 
reclassifying a device from rulemaking to an administrative order. 
Section 608(b) of FDASIA amended section 515(b) of the FD&C Act 
changing the process for requiring premarket approval for a 
preamendments class III device from rulemaking to an administrative 
order.

A. Reclassification

    FDA is publishing this document to propose the reclassification of 
intra-aortic balloon and control system devices when indicated for 
acute coronary syndrome, cardiac and non-

[[Page 36704]]

cardiac surgery, or complications of heart failure 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, 388-391 (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 intra-aortic balloon and control system 
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, which 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 intra-aortic balloon and 
control system devices when indicated for septic shock or pulsatile 
flow generation.
    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, payers, 
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 intra-
aortic balloon and control system 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) 
the 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 intra-aortic 
balloon and control system 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 7939; February 5, 1980). 
Therefore, if the proposal to require premarket approval for intra-
aortic balloon and control system devices indicated for septic shock or 
pulsatile flow generation 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

[[Page 36705]]

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) of the FD&C Act, interested 
persons are being offered the opportunity to request reclassification 
of intra-aortic balloon and control system devices indicated for septic 
shock or pulsatile flow generation.

II. Regulatory History of the Device

    In the preamble to the proposed rule (44 FR 13369; March 9, 1979), 
the Cardiovascular Device Classification Panel (the 1979 Panel) 
recommended that intra-aortic balloon and control system devices be 
classified into class III because the device is life-supporting, and 
there was insufficient medical and scientific information to establish 
a standard to assure the safety and effectiveness of the device. The 
1979 Panel noted that controversy exists as to whether the device is 
beneficial in many situations in which it is used and that it is 
difficult to use the device safely and effectively. The 1979 Panel 
further noted that accurate and precise labeling and directions for use 
are especially critical and voiced concern that the various components 
of the device would not function properly if its modular components 
were poorly matched. The 1979 Panel indicated that the balloon of the 
device is used within the main artery of the body and because this 
portion of the device is in contact with internal tissues and blood, 
the materials used with it require special controls, and because the 
device is electrically powered and portions of the device may be in 
direct contact with the heart, the electrical characteristics of the 
device, e.g., electrical leakage current, need to meet certain 
requirements. Additionally, if the design of the device is inadequate 
for accurate and precise blood pumping, a resulting failure could lead 
to death. Consequently, the 1979 Panel believed that premarket approval 
was necessary to assure the safety and effectiveness of the device. In 
1980, FDA classified intra-aortic balloon and control system devices 
into class III after receiving no comments on the proposed rule (45 FR 
7939; February 5, 1980).
    In 1987, FDA published a clarification by inserting language in the 
codified language stating that no effective date had been established 
for the requirement for premarket approval for intra-aortic balloon and 
control system devices (52 FR 17736; May 11, 1987).
    In 2009, FDA published an order for the submission of information 
on intra-aortic balloon and control system devices by August 7, 2009 
(74 FR 16214; April 9, 2009). FDA received four responses to that order 
from device manufacturers. One manufacturer stated in their response 
that they were ``not aware of adequate and valid scientific information 
that would support reclassification of the device to Class I or II.'' 
The other three manufacturers recommended that intra-aortic balloon and 
control system devices be reclassified to class II. The manufacturers 
stated that safety and effectiveness of these devices may be assured 
based on data available in the clinical literature; preclinical and 
clinical testing; 40 or more years of knowledge and information 
regarding the clinical use of the devices; and the overall number of 
marketed devices.
    As explained further in sections VII and XI of this document, a 
meeting of the Circulatory System Devices Panel (the 2012 Panel) took 
place December 5, 2012, to discuss whether intra-aortic balloon and 
control system devices should be reclassified or remain in class III. 
The 2012 Panel recommended that intra-aortic balloon and control system 
devices be reclassified to class II with special controls when 
indicated for acute coronary syndrome, cardiac and non-cardiac surgery, 
or complications of heart failure based on available evidence that 
supports the safety and effectiveness of the devices for these uses and 
the ability of special controls to mitigate identified risks to health. 
The 2012 Panel also recommended that intra-aortic balloon and control 
system devices indicated for septic shock or pulsatile flow generation 
remain in class III because the devices are life-supporting and 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 intra-aortic balloon and control system, also known as an intra-
aortic balloon pump (IABP), consists of a balloon, which inflates and 
deflates in synchronization with the cardiac cycle, and console, which 
provides the pneumatic flow of helium to the balloon so that it can 
inflate and deflate. The balloon is usually manufactured from 
polyurethane. It is inserted through the femoral artery and resides in 
the descending aorta. Conventional timing sets inflation of the balloon 
to occur at the onset of diastole or the aortic valve closure 
timepoint. During diastole, the balloon will inflate, increasing blood 
flow to the coronary arteries, therefore increasing myocardial oxygen 
supply. The balloon remains inflated throughout the diastolic phase, 
maintaining the increased pressure in the aorta. The deflation of the 
balloon takes place at the onset of systole during the isovolumetric 
contraction or very early in the systolic ejection phase. This 
deflation will cause a decrease in pressure in the aorta and this 
decrease in pressure assists the left ventricle by reducing the 
pressure that needs to be generated to achieve ejection through the 
aortic valve. As the balloon deflates during systole, it increases 
blood flow to the systemic circulation by reducing afterload and also 
decreases the oxygen demand of the myocardium.
    The console includes software that controls the inflation and 
deflation of the balloon based upon the patient's electrocardiogram or 
arterial pressure waveform. The console also controls the amount of 
helium that is transferred from the internal helium cylinder to the 
balloon. Most balloons come in sizes of 30cc, 40cc, and 50cc with a 
catheter diameter of 7.5Fr or 8Fr.

IV. Proposed Reclassification

    FDA is proposing that intra-aortic balloon and control system 
devices when indicated for acute coronary syndrome, cardiac and non-
cardiac surgery, or complications of heart failure 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

[[Page 36706]]

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 when indicated for acute 
coronary syndrome, cardiac and non-cardiac surgery, or complications of 
heart failure. 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 intra-aortic 
balloon and control system devices when indicated for acute coronary 
syndrome, cardiac and non-cardiac surgery, or complications of heart 
failure.
    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 intra-aortic balloon and control system devices when 
indicated for acute coronary syndrome, cardiac and non-cardiac surgery, 
or complications of heart failure in accordance with the reserved 
criteria set forth in section 513(a) of the FD&C Act and decided that 
the device requires 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 intra-aortic balloon and control system 
devices and determined that the following risks to health are 
associated with its use:
     Cardiac arrhythmias or electrical shock: Excessive 
electrical leakage current can disturb the normal electrophysiology of 
the heart, leading to the onset of cardiac arrhythmias.
     Ineffective cardiac assist (poor augmentation): Failure to 
sense or synchronize on heartbeat, failure to inflate and deflate at 
the proper intervals, and/or failure of the balloon to fully unwrap can 
lead to improper or ineffective pumping of blood.
     Thromboembolism: Inadequate blood compatibility of the 
materials used in this device and/or inadequate surface finish and 
cleanliness can lead to potentially debilitating or fatal 
thromboemboli.
     Aortic rupture or dissection: Improper sizing or over 
inflation of the balloon can cause a rupture in the main artery.
     Limb ischemia: Improper operation of the device which 
restricts blood flow to the peripheral vascular tree results in tissue 
ischemia in the limbs.
     Gas embolism: Balloon rupture or a leak in the balloon can 
cause potentially debilitating or fatal gas emboli to escape into the 
bloodstream.
     Hemolysis: Poor material-blood compatibility or excessive 
disruption of the normal hemodynamic flow patterns can cause hemolysis.
     Infection: Defects in the design or construction of the 
device preventing adequate sterilization can allow pathogenic organisms 
to be introduced and may cause an infection in a patient.
     Insertion site bleeding: Improper sizing of the cannula 
can cause trauma to the artery during insertion of the catheter.
     Thrombus/large blood clots: Leaks of the membrane (balloon 
surface) or catheter can result in gaseous embolic injury of organs or 
cause a large blood clot to form within the balloon membrane requiring 
surgical removal of the catheter.
     Balloon entrapment: A balloon perforation can cause blood 
to enter the balloon forming a large hardened mass of blood within the 
balloon. This can cause the balloon to become ``entrapped ``in the 
femoral/iliac system upon removal. Balloon entrapment is characterized 
by undue resistance to balloon removal.
     Insertion difficulty/inability to insert the catheter: 
Device sizing, insertion technique and/or patient anatomy, specifically 
tortuous and/or narrowed femoral arteries, can cause insertion 
difficulties. As a result, therapy can be delayed and there could be an 
increased risk of vascular damage and/or bleeding due to forceful 
insertion.
     Vessel occlusion resulting in ischemia, infarction to an 
organ (including paraplegia) and/or compartment syndrome: Malposition 
of the balloon can compromise circulation due to large vessel occlusion 
from catheter migration, resulting in ischemia, infarction to an organ 
or increased compartment pressures, leading to muscle and nerve damage. 
Vessel occlusion can also be caused by dislodged atherosclerotic plaque 
and/or clots.
     Thrombocytopenia: Improper inflation of the balloon can 
cause a drop in platelets.
     Stroke: Mechanical disruption of atheroma or thrombus 
liberation causing embolism; disruption of the cranial circulation by 
the balloon, including obstruction, dissection or perforation; or 
complications resulting from the use of anticoagulation, can lead to 
stroke.
     Death: Mechanical failure of the device, vascular 
complications or bleeding can lead to death.

VI. Summary of Reasons for Reclassification

    If properly manufactured and used as intended, intra-aortic balloon 
and control system devices can provide a treatment option for patients 
when indicated for acute coronary syndrome, cardiac and non-cardiac 
surgery, or complications of heart failure, by increasing myocardial 
oxygen supply, decreasing myocardial oxygen demand, and improving 
cardiac output. FDA believes that intra-aortic balloon and control 
system devices indicated for acute coronary syndrome, cardiac and non-
cardiac surgery, or complications of heart failure, should be 
reclassified from class III to class II because, in light of new 
information about the effectiveness of these devices, FDA believes that 
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.

VII. Summary of Data Upon Which the Reclassification Is Based

    Since the time of the original 1979 Panel recommendation, 
sufficient evidence has been developed to support a reclassification of 
intra-aortic balloon and control system devices to class II with 
special controls when indicated for acute coronary syndrome, cardiac 
and non-cardiac surgery, or complications of heart failure. FDA has 
been reviewing these devices for many years and their risks are well 
known. FDA conducted a comprehensive review of available literature for 
IABP devices for acute coronary syndrome, cardiac and non-cardiac 
surgery, and complications of heart failure. FDA's review found 18 
cohort studies (9 retrospective and 9 prospective), 6 randomized 
controlled trials, 3 case-control studies, 2 case series, 4 systematic 
reviews, and a meta-analysis, which provided consistent evidence of the 
safety and effectiveness of intra-aortic balloon and control system 
devices for acute coronary syndrome, cardiac and non-cardiac surgery, 
and complications of heart failure.

[[Page 36707]]

    Collectively these studies support that the overall complication 
rates for intra-aortic balloon and control systems is low. For example, 
in the Benchmark Registry (Ref. 1), there were low IABP complication 
rates, including IABP-related mortality (0.05 percent and 0.07 percent 
in the United States and European Union, respectively), major limb 
ischemia (0.09 percent, 0.8 percent) and severe bleeding (0.9 percent, 
0.8 percent). This is consistent with other studies of IABP use with 
large sample sizes. Additionally, in the most recently published trial 
of IABP use, the IABP SHOCK II trial (Ref. 2), published in October 
2012, 600 patients were randomized to IABP (301 patients) or no IABP 
(299 patients). The IABP group and the control group did not differ 
significantly with respect to the rates of adverse events, including 
major bleeding (3.3 percent and 4.4 percent, respectively; P = 0.51), 
peripheral ischemic complications (4.3 percent and 3.4 percent, P = 
0.53), sepsis (15.7 percent and 20.5 percent, P = 0.15), and stroke 
(0.7 percent and 1.7 percent, P = 0.28). These rates represent recent 
IABP usage outcomes in a randomized trial of patients with high 
associated morbidity using modern aggressive interventional approaches 
to acute myocardial infarction (MI) and cardiogenic shock, which 
include the use of percutaneous coronary intervention and aggressive 
anticoagulation. The trial demonstrates low rates of adverse events 
that can be attributed directly to the IABP itself.
    It is important to note that the patients in whom IABP is used have 
severe comorbidities and underlying illnesses. As a result, overall 
mortality in these patients is high. Patients recruited for studies on 
the IABP are of a population segment that is at an inherently greater 
risk of mortality because of the high-risk procedures they require, and 
the illnesses that necessitated the procedures. Additionally, there are 
trends to less balloon-related mortality over time, as balloon catheter 
sizes have decreased and procedural techniques have improved.
    The literature data also supports the effectiveness of IABP for 
acute coronary syndrome, cardiac and non-cardiac surgery, and 
complications of heart failure. With respect to acute coronary 
syndrome, the Benchmark Registry (Ref. 1) demonstrated that the 
mortality of patients with cardiogenic shock was 30.7 percent, which 
was low compared to other cardiogenic shock trials, and has been cited 
as evidence of a benefit from IABP use. Further evaluation of this 
registry has shown that in U.S. patients, compared to patients outside 
the United States (OUS), an IABP was placed at earlier stages of the 
disease. After appropriate adjustment of risk factors, U.S. patients 
showed decreased mortality (10.8 percent (U.S.) vs. 18 percent (OUS), P 
< 0.001). The results of the Global Utilization of Streptokinase and 
Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1 
trial) (Ref. 3) also demonstrated a 12-month survival advantage in 
cardiogenic shock with early IABP implantation. This was a 
retrospective study of IABP use in patients presenting with acute MI 
and cardiogenic shock who received systemic fibrinolysis. Sixty-eight 
of 310 cardiogenic shock patients received an IABP. The significantly 
higher frequency of IABP use in the United States in relation to Europe 
in these two trials was associated with more bleeding complications, 
but also with a lower mortality rate, both nonsignificantly at 30 days 
(47 percent vs. 60 percent) and significantly at 1 year (57 percent vs. 
67 percent). This mortality benefit is also supported by two 
publications regarding the National Registry of Myocardial Infarction 
(Refs. 4 and 5).
    The literature regarding the effectiveness of IABPs in cardiac and 
non-cardiac surgery has demonstrated utility in some studies and in 
others has been equivocal in demonstrating effectiveness. However, FDA 
and the 2012 Panel (as described in further detail in this document) 
find that there are certain subgroups of patients that may benefit from 
IABP use for cardiac and non-cardiac surgery indications. This is 
demonstrated in Christenson et al. (Ref. 6), which randomized 30 high-
risk off-pump coronary artery bypass graft (CABG) surgery recipients to 
receive an IABP preoperatively or no IABP. The use of an IABP improved 
preoperative and postoperative cardiac performance significantly (P < 
0.0001). The postoperative course was also improved, including 
decreased pneumonia and acute renal failure, shorter duration of 
ventilator support, and fewer patients requiring postoperative 
inotropic medications for greater than 48 hours. The lengths of stay in 
the intensive care unit and in the hospital were shorter in the IABP 
group. Additionally, Miceli et al. (Ref. 7) studied 141 consecutive 
patients from 2004-2007 undergoing CABG, in which 38 patients (27 
percent) received a prophylactic IABP. After risk-adjusting for 
propensity score, prophylactic IABP patients had a lower incidence of 
postcardiotomy low cardiac output syndrome (adjusted OR 0.07, P < 
0.006) and postoperative myocardial infarction (adjusted OR 0.04, P < 
0.04), as well as a shorter length of hospital stay (10.40.8 vs. 12.20.6 days, P < 0.0001) compared to those 
who did not receive an IABP.
    Much of the evidence that supports the effectiveness of an IABP for 
complications of heart failure is outlined previously in this document 
with respect to acute coronary syndrome (e.g., cardiogenic shock from 
acute MI). However, there are additional smaller studies that support 
use in heart failure specifically, including bridge to transplant and 
acute decompensated dilated cardiomyopathy. For example, Norkiene et 
al. (Ref. 8) studied 11 patients with decompensated dilated 
cardiomyopathy (CMP) listed for heart transplant who were recorded in 
the Benchmark Registry from September 2004 to December 2005, with New 
York Heart Association Class IV functional status. Frequency of 
complications and clinical outcomes were assessed prior to and after 
IABP insertion as well as hemodynamics and end-organ function (renal 
and hepatic). After 48 hours of IABP support, there was a significant 
increase of mean systemic arterial pressure from 74.59.6 to 
82.34.7 mmHg (P = 0.02), and ejection fraction from 
14.76.4 to 21.08.6 (P = 0.014). Improvement of 
the cardiac index, pulmonary wedge pressure, and end-organ perfusion 
markers did not reach statistical significance. The authors concluded 
that IABP support may be successfully and safely used in acute 
decompensated dilated cardiomyopathy patients as an urgent measure of 
cardiac support to stabilize the patient and maintain organ perfusion 
until transplant is available, ventricular assist device is placed, or 
the patient is weaned from the IABP.
    Rosenbaum et al. (Ref. 9) studied 43 patients with end-stage 
congestive heart failure in whom an IABP was used as a bridge to 
transplant. Twenty-seven patients had non-ischemic CMP (NICM), and 16 
had ischemic CMP (ISCM). Hemodynamics improved in both groups, 
immediately (15 to 30 minutes) following IABP insertion, with greater 
improvement (p < 0.05) in cardiac index and a trend toward greater 
reduction in filling pressures in the NICM group. Systemic vascular 
resistance fell to a similar degree in both groups. During continued 
IABP support (0.13 to 38 days in NICM, 1 to 54 days in ISCM), all 
hemodynamic changes persisted in both groups, with a larger decrease (p 
< 0.05) in systemic vascular resistance and greater increase (p < 0.05) 
in cardiac index in the patients with NICM. The reduction in filling 
pressures, however, tended to be greater in patients with

[[Page 36708]]

ISCM. Complications from the IABP were low. The authors concluded that 
IABP use was both safe and effective in this group as a bridge to 
transplant.
    The literature data outlined previously in this document supports a 
conclusion of reasonable evidence for the safety and effectiveness of 
intra-aortic balloon and control system devices when indicated for 
acute coronary syndrome, cardiac and non-cardiac surgery, and 
complications of heart failure. In addition, bench studies designed to 
demonstrate the devices' ability to function as intended have been well 
characterized.
    FDA's presentation to the 2012 Panel included a summary of the 
available safety and effectiveness information for intra-aortic balloon 
and control system devices when indicated for acute coronary syndrome, 
cardiac and non-cardiac surgery, or complications of heart failure, 
including adverse event reports from FDA's Manufacturer and User 
Facility Device Experience (MAUDE) database and available literature. 
Based on the available scientific literature, which supports that use 
of intra-aortic balloon and control system devices may be beneficial 
for patients when indicated for acute coronary syndrome, cardiac and 
non-cardiac surgery, or complications of heart failure, FDA recommended 
to the 2012 Panel that intra-aortic balloon and control system devices 
indicated for acute coronary syndrome, cardiac and non-cardiac surgery, 
or complications of heart failure be reclassified to class II (special 
controls). The 2012 Panel discussed and made recommendations regarding 
the regulatory classification of intra-aortic balloon and control 
system 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. The 2012 Panel 
agreed with FDA's conclusion that the available scientific evidence is 
adequate to support the safety and effectiveness of intra-aortic 
balloon and control system devices when indicated for acute coronary 
syndrome, cardiac and non-cardiac surgery, or complications of heart 
failure. Several members of the 2012 Panel noted that not all available 
data supports the effectiveness of the device conclusively; however, 
there was consensus that IABPs improve hemodynamics and provide an 
important tool for clinicians in treating a patient population with 
high morbidity and mortality. The 2012 Panel also acknowledged that 
intra-aortic balloon and control systems are life-supporting devices 
and provided the following rationale per Sec.  860.93 for recommending 
that IABPs for acute coronary syndrome, cardiac and non-cardiac 
surgery, or complications of heart failure be reclassified to class II: 
(1) There is a wealth of clinical experience that attests to the 
benefit of the device; (2) there is an important advantage to use of 
intra-aortic balloon counter-pulsation to provide hemodynamic stability 
or protection from ischemia in precarious or unstable patients; and (3) 
the recommended special controls will mitigate the health risks 
associated with the device.
    The 2012 Panel also agreed with the identified risks to health 
presented at the meeting; however, the 2012 Panel recommended that 
compartment syndrome, death, and stroke be added to the list of risks 
to health and that ischemia be added to ``vessel occlusion resulting in 
infarction to an organ (including paraplegia)''. FDA agrees with the 
2012 Panel's recommendations and modified the risks to health 
accordingly as outlined in section V. The 2012 Panel also agreed with 
FDA's proposed special controls outlined in section VIII; however, the 
2012 Panel further recommended that information about IABP clinical 
trials should be added to the device labeling as a special control. FDA 
does not agree with this recommendation from the 2012 Panel. FDA 
determined that it was not appropriate to require that clinical trial 
information be included in the device labeling as a special control 
because available clinical trial information would most accurately 
represent the device type, not individual devices, so including such 
information in the labeling for a specific device may be misleading. On 
this basis, the special controls outlined in section VIII were not 
modified based on this recommendation from the 2012 Panel.
    The 2012 Panel transcript and other meeting materials are available 
on FDA's Web site (Ref. 10).

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) Appropriate analysis and non-clinical 
testing must be conducted to validate electromagnetic compatibility and 
electrical safety of the device; (2) appropriate software verification, 
validation, and hazard analysis must be performed; (3) the device must 
be demonstrated to be biocompatible; (4) sterility and shelf life 
testing must demonstrate the sterility of patient-contacting components 
and the shelf life of these components; (5) non-clinical performance 
evaluation of the device must provide a reasonable assurance of safety 
and effectiveness for mechanical integrity, durability, and 
reliability; and (6) labeling must bear all information required for 
the safe and effective use of the device, including a detailed summary 
of the device- and procedure-related complications pertinent to use of 
the device.
    Intra-aortic balloon and control system 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 
21 CFR 870.3535(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 controls 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 21 CFR 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 for intra-aortic balloon 
and control systems indicated for septic shock or pulsatile flow 
generation 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 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 septic shock or pulsatile flow generation, 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. Under 21 
CFR 806.10(a)(2) a device manufacturer or importer initiating a 
correction to remedy a violation of the FD&C Act that

[[Page 36709]]

may present a risk to health is required 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 intra-aortic balloon and control systems indicated for 
acute coronary syndrome, cardiac and non-cardiac surgery, or 
complications of heart failure, 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 intra-aortic 
balloon and control systems indicated for acute coronary syndrome, 
cardiac and non-cardiac surgery, or complications of heart failure.

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 when indicated for septic shock or 
pulsatile flow generation and (2) the benefits to the public from the 
use of intra-aortic balloon and control systems indicated for septic 
shock or pulsatile flow generation.
    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 device type is discussed in Section 
XI B., Summary of Data, and can also be found in 44 FR 13284-13434, 
March 9, 1979; 45 FR 7907-7971, February 5, 1980; and 52 FR 17736, May 
11, 1987.

XI. Device Subject to the Proposal To Require a PMA--Intra-Aortic 
Balloon and Control System Devices When Indicated for Septic Shock or 
Pulsatile Flow Generation (Sec.  870.3535(c))

A. Identification

    An intra-aortic balloon and control system is a prescription device 
that consists of an inflatable balloon, which is placed in the aorta to 
improve cardiovascular functioning during certain life-threatening 
emergencies, and a control system for regulating the inflation and 
deflation of the balloon. The control system, which monitors and is 
synchronized with the electrocardiogram, provides a means for setting 
the inflation and deflation of the balloon with the cardiac cycle.

B. Summary of Data

    When indicated for septic shock or pulsatile flow generation, 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 intra-aortic balloon 
and control system devices for these indications. Specifically, based 
on FDA's review of the published scientific literature, it appears that 
there are no studies regarding intra-aortic balloon and controls 
systems indicated for septic shock in humans. The use of the IABP for 
pulsatile flow generation made up less than 1 percent of the 
indications for use evaluated in FDA's literature search. Three 
observational studies regarding pulsatile flow generation were found 
during FDA's review of the literature. All three articles state that 
the device is associated with low mortality and adverse event rates; 
however, none of the studies was stratified by indication. As a result, 
it cannot be concluded that these results apply to septic shock or 
pulsatile flow generation specifically.
    FDA presented the findings of our literature search for intra-
aortic balloon and control system devices for the indications of septic 
shock and pulsatile flow generation to the 2012 Panel on December 5, 
2012. Based on FDA's findings, the Panel recommended that available 
scientific evidence is not adequate to support the effectiveness of 
intra-aortic balloon and control system devices for the indications of 
septic shock or pulsatile flow generation. As a result, the 2012 Panel 
concluded that intra-aortic balloon and control system devices for the 
indications of septic shock or pulsatile flow generation should remain 
in class III (subject to premarket approval application). The 2012 
Panel transcript and other meeting materials are available on FDA's Web 
site (Ref. 10).

C. Risks to Health

    The risks to health for intra-aortic balloon and control system 
devices for the indications of septic shock or pulsatile flow 
generation are the same as outlined in section V.

D. Benefits of Intra-Aortic Balloon and Control System Devices

    As discussed previously in this document, there is limited 
scientific evidence regarding the effectiveness of intra-aortic balloon 
and control system devices for the indications of septic shock or 
pulsatile flow generation. For indications of septic shock, the 
hemodynamic effects generated by use of intra-aortic balloon and 
control systems do not address the fundamental hemodynamic derangements 
of septic shock syndrome. FDA is not aware of any theoretical or 
demonstrated benefit to using intra-aortic balloon and control systems 
for this clinical syndrome. For indications of pulsatile flow 
generation, it is impossible to estimate the direct effect of the 
devices on patient outcomes based on the lack of effectiveness data for 
this indication as described previously.

XII. PMA Requirements

    A PMA for intra-aortic balloon and control system devices indicated 
for septic shock or pulsatile flow generation 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

[[Page 36710]]

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 intra-aortic 
balloon and control system devices indicated for septic shock or 
pulsatile flow generation 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.  
870.4360 related to the classification of non-roller type 
cardiopulmonary and circulatory bypass blood pump devices as class III 
devices and to codify the reclassification of non-roller type 
cardiopulmonary and circulatory bypass blood pump devices 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, if finalized, 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 21 CFR 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 https://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 https://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 https://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. Cohen, M., P. Urban, J.T. Christenson, et al., ``Intra-Aortic 
Balloon Counterpulsation in U.S. and non-U.S. Centres: Results of 
the Benchmark (Registered Trademark) Registry,'' European Heart 
Journal, vol. 24, pp. 1763-1770, 2003.
2. Thiele, H., U. Zeymer, F.J. Neumann, et al. for the IABP-SHOCK II 
Trial Investigators, ``Intraaortic Balloon Support for Myocardial 
Infarction With Cardiogenic Shock.'' New England Journal of 
Medicine, vol. 367, pp. 1287-1296, 2012.
3. Anderson, R.D., M.E. Ohman, and D.R. Holmes for the GUSTO-I 
Investigators, ``Use of Intraaortic Balloon Counterpulsation in 
Patients Presenting With Cardiogenic Shock: Observations from the 
GUSTO-I Study,'' Journal of the American College of Cardiology, vol. 
30, pp. 708-715, 1997.
4. Chen, E.W., J.G. Canto, L.S. Parsons, et al., ``Relation Between 
Hospital Intra-Aortic Balloon Counterpulsation Volume and Mortality 
in Acute Myocardial Infarction Complicated by Cardiogenic Shock,'' 
Circulation, vol. 108, pp. 951-957, 2003.
5. Barron, H.V., N.R. Every, L.S. Parsons, et al., ``The Use of 
Intraaortic Balloon Counterpulsation in Patients With Cardiogenic 
Shock Complicating Acute Myocardial Infarction: Data From the 
National Registry of Myocardial Infarction 2,'' American Heart 
Journal, vol. 141, pp. 933-939, 2001.
6. Christenson, J.T., M. Licker, and A. Kalangos, ``The Role of 
Intraaortic Counterpulsion in High Risk OPCAB Surgery: A Prospective 
Randomised Study,'' Journal of Cardiac Surgery, vol. 18, pp. 286-
294, 2003.

[[Page 36711]]

7. Miceli, A., B. Fiorani, T.H. Danesi, et al., ``Prophylactic 
Intra-Aortic Balloon Pump in High-Risk Patients Undergoing Coronary 
Artery Bypass Grafting: A Propensity Score Analysis,'' Interactive 
Cardiovascular and Thoracic Surgery, vol. 9, pp. 291-294, 2009.
8. Norkiene, I., D. Ringaitiene, K. Rucinskas, et al., ``Intra-
Aortic Balloon Counterpulsation in Decompensated Cardiomyopathy 
Patients: Bridge to Transplantation or Assist Device.'' Interactive 
Cardiovascular and Thoracic Surgery, vol. 6, pp. 66-70, 2007.
9. Rosenbaum, A.M., S. Murali, and B.F. Uretsky, ``Intra-Aortic 
Balloon Counterpulsation as a `Bridge' to Cardiac Transplantation. 
Effects in Nonischemic and Ischemic Cardiomyopathy,'' Chest, vol. 
106, pp. 1683-1688, 1994.
10. The panel transcript and other meeting materials are available 
on FDA's Web site, available at https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm300073.htm.

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.  870.3535 to read as follows:


Sec.  870.3535  Intra-aortic balloon and control system.

    (a) Identification. An intra-aortic balloon and control system is a 
prescription device that consists of an inflatable balloon, which is 
placed in the aorta to improve cardiovascular functioning during 
certain life-threatening emergencies, and a control system for 
regulating the inflation and deflation of the balloon. The control 
system, which monitors and is synchronized with the electrocardiogram, 
provides a means for setting the inflation and deflation of the balloon 
with the cardiac cycle.
    (b) Classification. (1) Class II (special controls) when the device 
is indicated for acute coronary syndrome, cardiac and non-cardiac 
surgery, or complications of heart failure. The special controls for 
this device are:
    (i) Appropriate analysis and non-clinical testing must be conducted 
to validate electromagnetic compatibility and electrical safety of the 
device;
    (ii) Appropriate software verification, validation, and hazard 
analysis must be performed;
    (iii) The device must be demonstrated to be biocompatible;
    (iv) Sterility and shelf life testing must demonstrate the 
sterility of patient-contacting components and the shelf life of these 
components;
    (v) Non-clinical performance evaluation of the device must provide 
a reasonable assurance of safety and effectiveness for mechanical 
integrity, durability, and reliability; and
    (vi) Labeling must bear all information required for the safe and 
effective use of the device, including a detailed summary of the 
device- and procedure-related complications pertinent to use of the 
device.
    (2) Class III (premarket approval) when the device is indicated for 
septic shock and pulsatile flow generation.
    (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 90 DAYS AFTER DATE OF PUBLICATION OF A 
FUTURE FINAL ORDER IN THE FEDERAL REGISTER], for any intra-aortic 
balloon and control system indicated for septic shock or pulsatile flow 
generation that was in commercial distribution before May 28, 1976, or 
that has, on or before [A DATE WILL BE ADDED 90 DAYS AFTER DATE OF 
PUBLICATION OF A FUTURE FINAL ORDER IN THE FEDERAL REGISTER], been 
found to be substantially equivalent to any intra-aortic balloon and 
control system indicated for septic shock or pulsatile flow generation 
that was in commercial distribution before May 28, 1976. Any other 
intra-aortic balloon and control system indicated for septic shock or 
pulsatile flow generation shall have an approved PMA or declared 
completed PDP in effect before being placed in commercial distribution.

    Dated: June 12, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-14553 Filed 6-18-13; 8:45 am]
BILLING CODE 4160-01-P