Premarket Notification Submission 5100(k), Subpart E

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significant regulatory action as defined
by Executive Order 12866.
The Regulatory Flexibility Act
requires Agencies to analyze regulatory
options that would minimize any
significant impact of a rule on small
entities. Because the proposed
reclassification would relieve
manufacturers of premarket approval
requirements of section 515 of the FD&C
Act (21 U.S.C. 360e) it would not create
new burdens. Thus, the Agency
proposes to certify that the proposed
rule, if finalized, will not have a
significant economic impact on a
substantial number of small entities.
Section 202(a) of the Unfunded
Mandates Reform Act of 1995 requires
that Agencies prepare a written
statement, which includes an
assessment of anticipated costs and
benefits, before proposing ‘‘any rule that
includes any Federal mandate that may
result in the expenditure by State, local,
and tribal governments, in the aggregate,
or by the private sector, of $100,000,000
or more (adjusted annually for inflation)
in any one year.’’ The current threshold
after adjustment for inflation is $139
million, using the most current (2011)
Implicit Price Deflator for the Gross
Domestic Product. FDA does not expect
this proposed rule, if finalized, to result
in any 1-year expenditure that would
meet or exceed this amount.
Our estimate of benefits annualized
over 20 years is $11.85 million at a 3
percent discount rate and $7.83 million
at a 7 percent discount rate. The change
in pre- and post-marketing requirements
between a 510(k) and a PMA lead to
benefits in the form of reduced
submission costs, review-related
activities, and inspections. Another
unquantifiable benefit from the rule is
that a decrease in entry could lead to
further product innovation. FDA is
unable to quantify the costs that could
arise if there is a change in risk which
could lead to adverse events, recalls,
warning letters, or unlisted letters.
The full discussion of economic
impacts is available in docket FDA–
2013–N–0544 at http://
www.regulations.gov, and at http://
www.fda.gov/AboutFDA/
ReportsManualsForms/Reports/
EconomicAnalyses/default.htm (Ref. 4).
XV. Comments
Interested persons may submit either
electronic comments regarding this
document or the associated Special
Controls guideline to http://
www.regulations.gov or written
comments to the Division of Dockets
Management (see ADDRESSES). It is only
necessary to send one set of comments.
Identify comments with the docket

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number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday, and
will be posted to the docket at http://
www.regulations.gov.
XVI. References
The following references have been
placed on display in the Dockets
Management Branch (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
all the Web site addresses in this
reference section, but we are not
responsible for any subsequent changes
to the Web sites after this document
publishes in the Federal Register.)
1. Transcript of the Tuberculosis Public
Workshop, June 7, 2010, (Available at: http://
www.fda.gov/downloads/ScienceResearch/
SpecialTopics/CriticalPathInitiative/
UpcomingEventsonCPI/UCM289182.doc,
accessed on January 25, 2012.)
2. Transcript of FDA’s Microbiology
Devices Panel Meeting, June 29, 2011.
(Available at: http://www.fda.gov/
downloads/AdvisoryCommittees/
CommitteesMeetingMaterials/
MedicalDevices/
MedicalDevicesAdvisoryCommittee/
MicrobiologyDevicesPanel/UCM269469.pdf.)
3. ‘‘Updated Guidelines for the Use of
Nucleic Acid Amplification Tests in the
Diagnosis of Tuberculosis,’’ Morbidity and
Mortality Weekly Report (MMWR), vol. 58,
pp. 7–10, January 16, 2009. (Available at:
http://www.cdc.gov/mmwr/preview/
mmwrhtml/mm5801a3.htm, accessed on July
26, 2011.)
4. Full Disclosure Preliminary Regulatory
Impact Analysis of the proposed rule
‘‘Microbiology Devices; Reclassification of
Nucleic Acid-Based Systems for
Mycobacterium tuberculosis Complex in
Respiratory Specimens,’’ Docket No. FDA–
2013–N–0544.

List of Subjects in 21 CFR Part 866
Biologics, Laboratories, Medical
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 866 is amended as follows:
PART 866—IMMUNOLOGY AND
MICROBIOLOGY DEVICES
1. The authority citation for part 866
continues to read as follows:

■

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

2. Add § 866.3372 to subpart D to read
as follows:

■

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§ 866.3372 Nucleic acid-based in vitro
diagnostic devices for the detection of
Mycobacterium tuberculosis complex in
respiratory specimens.

(a) Identification. Nucleic acid-based
in vitro diagnostic devices for the
detection of Mycobacterium
tuberculosis complex in respiratory
specimens are qualitative nucleic acidbased in vitro diagnostic devices
intended to detect Mycobacterium
tuberculosis complex nucleic acids
extracted from human respiratory
specimens. These devices are nonmultiplexed and intended to be used as
an aid in the diagnosis of pulmonary
tuberculosis when used in conjunction
with clinical and other laboratory
findings. These devices do not include
devices intended to detect the presence
of organism mutations associated with
drug resistance. Respiratory specimens
may include sputum (induced or
expectorated), bronchial specimens
(e.g., bronchoalveolar lavage or
bronchial aspirate), or tracheal aspirates.
(b) Classification. Class II (special
controls). The special control for this
device is the FDA document entitled
‘‘Class II Special Controls Guideline:
Nucleic Acid-Based In Vitro Diagnostic
Devices for the Detection of
Mycobacterium tuberculosis Complex in
Respiratory Specimens.’’ For availability
of the guideline document, see
§ 866.1(e).
Dated: June 12, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013–14552 Filed 6–18–13; 8:45 am]
BILLING CODE 4160–01–P

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 NonCardiac 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

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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.

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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

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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

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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 intraaortic balloon and control system
devices when indicated for acute
coronary syndrome, cardiac and non-

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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 § 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.

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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

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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 intraaortic 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

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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

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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 intraaortic 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 lifesupporting 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.

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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

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Act and § 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 noncardiac 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.

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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

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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.

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• 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 noncardiac 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 metaanalysis, 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.

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Collectively these studies support that
the overall complication rates for intraaortic balloon and control systems is
low. For example, in the Benchmark
Registry (Ref. 1), there were low IABP
complication rates, including IABPrelated 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.
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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 highrisk 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

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(adjusted OR 0.04, P < 0.04), as well as
a shorter length of hospital stay
(10.4±0.8 vs. 12.2±0.6 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 74.5±9.6 to 82.3±4.7
mmHg (P = 0.02), and ejection fraction
from 14.7±6.4 to 21.0±8.6 (P = 0.014).
Improvement of the cardiac index,
pulmonary wedge pressure, and endorgan 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

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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 intraaortic balloon and control system
devices when indicated for acute
coronary syndrome, cardiac and noncardiac 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 noncardiac 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 noncardiac 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 intraaortic balloon and control systems are
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the following rationale per § 860.93 for
recommending that IABPs for acute
coronary syndrome, cardiac and noncardiac 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 nonclinical 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 patientcontacting components and the shelf life
of these components; (5) non-clinical

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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 procedurerelated 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

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may present a risk to health is required
to submit a written report of the
correction to FDA.
FDA intends that under § 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 § 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 § 812.30.
FDA, therefore, recommends that IDE
applications be submitted to FDA at
least 30 days before the end of the 90day 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 noncardiac 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

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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 (§ 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.

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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

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Federal Register / Vol. 78, No. 118 / Wednesday, June 19, 2013 / Proposed Rules

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
§ 860.7(c)(1)). Valid scientific evidence
is ‘‘evidence from well-controlled
investigations, partially controlled
studies, studies and objective trials
without matched controls, welldocumented 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
§ 860.7(c)(2)).

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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 § 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

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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 § 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 nonroller 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.

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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.

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Federal Register / Vol. 78, No. 118 / Wednesday, June 19, 2013 / Proposed Rules
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/Committees
MeetingMaterials/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
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.

2. Revise § 870.3535 to read as
follows:

■

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§ 870.3535
system.

Intra-aortic balloon and control

(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 lifethreatening 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 nonclinical testing must be conducted to

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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 intraaortic 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 intraaortic 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

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36711

DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Chapter I
[Docket Nos. FDA–2013–N–0683, FDA–
2013–N–0684, and FDA–2013–N–0685]

Food and Drug Administration Safety
and Innovation Act Title VII—Drug
Supply Chain; Standards for
Admission of Imported Drugs,
Registration of Commercial Importers
and Good Importer Practices;
Notification of Public Meeting; Request
for Comments
AGENCY:

Food and Drug Administration,

HHS.
Notification of public meeting;
request for comments.

ACTION:

SUMMARY: The Food and Drug
Administration (FDA or Agency) is
announcing a public meeting regarding
FDA’s implementation of Title VII of the
Food and Drug Administration Safety
and Innovation Act (FDASIA), which
provides FDA with important new
authorities to help it better protect the
integrity of the drug supply chain. In
addition to providing a general
overview of Title VII and FDA’s
approach to implementing these
provisions, the meeting will give
interested persons an opportunity to
provide input that will assist FDA in the
development of regulations
implementing two sections of Title VII,
which relate to standards for admission
of imported drugs and commercial drug
importers. Specifically, FDA is seeking
information on the types of information
that importers should be required to
provide under Title VII as a condition
of admission. FDA is also seeking
information regarding registration
requirements for commercial drug
importers and good importer practices
to be established under Title VII.
DATES: The public meeting will be held
on July 12, 2013, from 9 a.m. to 5 p.m.
at the FDA White Oak Campus, 10903
New Hampshire Ave., Bldg. 31
Conference Center, the Great Room (rm.
1503), Silver Spring MD 20993. Please
note that visitors to the White Oak
Campus must enter through Building 1.
The White Oak Campus location is a
Federal facility with security procedures
and limited seating. There is no fee to
register for the meeting and registration
will be on a first come, first serve basis.
Early registration is recommended
because seating is limited. Onsite
registration will also be permitted if
there is available space. See section IV
of this document, ‘‘How to Participate in

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