[Federal Register Volume 78, Number 118 (Wednesday, June 19, 2013)]
[Proposed Rules]
[Pages 36702-36711]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-14553]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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: 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-0581 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,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background--Regulatory Authorities
The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L.
94-295), the Safe Medical Devices Act of 1990 (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 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. 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 http://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