[Federal Register Volume 78, Number 250 (Monday, December 30, 2013)]
[Rules and Regulations]
[Pages 79300-79303]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-31218]
[[Page 79300]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 870
[Docket No. FDA-2013-N-0581]
Cardiovascular Devices; Reclassification of Intra-Aortic Balloon
and Control Systems for Acute Coronary Syndrome, Cardiac and Non-
Cardiac Surgery, or Complications of Heart Failure; Effective Date of
Requirement for Premarket Approval for Intra-Aortic Balloon and Control
Systems for Septic Shock or Pulsatile Flow Generation
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a final
order to reclassify intra-aortic balloon and control system (IABP)
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), and to require the
filing of a premarket approval application (PMA) or a notice of
completion of a product development protocol (PDP) for IABPs when
indicated for septic shock or pulsatile flow generation.
DATES: This order is effective December 30, 2013.
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. Section 515(b)(1)
of the FD&C Act directs FDA to issue an order requiring premarket
approval for a preamendments class III device.
Although, under the FD&C Act, the manufacturer of a 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 mechanism 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 mechanism for requiring premarket approval for a
preamendments class III device from rulemaking to an administrative
order.
A. Reclassification
FDA is reclassifying IABP devices when indicated for acute coronary
syndrome, cardiac and non-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)
of the FD&C Act or an interested person may petition FDA to reclassify
a preamendments device. The term ``new information,'' as used in
section 513(e) of the FD&C Act, includes information developed as a
result of a reevaluation of the data before the Agency when the device
was originally 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) of the
FD&C Act must be ``valid scientific evidence,'' as defined in section
513(a)(3) of the FD&C Act and 21 CFR 860.7(c)(2). (See, e.g., General
Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir.
[[Page 79301]]
1985); Contact Lens Manufacturers Association v. FDA, 766 F.2d 592
(D.C. Cir. 1985), cert. denied, 474 U.S. 1062 (1986).)
FDA relies upon ``valid scientific evidence'' in the classification
process to determine the level of regulation for devices. To be
considered in the reclassification process, the ``valid scientific
evidence'' upon which the Agency relies must be publicly available.
Publicly available information excludes trade secret and/or
confidential commercial information, e.g., the contents of a pending
PMA. (See section 520(c) of the FD&C Act (21 U.S.C. 360j(c)).) Section
520(h)(4) of the FD&C Act, 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 held a meeting of
a device classification panel described in section 513(b) of the FD&C
Act with respect to IABP devices on December 5, 2012 (the 2012 Panel).
The 2012 Panel recommended that IABP devices indicated for acute
coronary syndrome, cardiac and non-cardiac surgery, or complications of
heart failure be reclassified to class II with special controls. The
2012 Panel agreed with FDA's conclusion that the available scientific
evidence is adequate to support the safety and effectiveness of IABP
devices indicated for acute coronary syndrome, cardiac and non-cardiac
surgery, or complications of heart failure. The 2012 Panel further
agreed that the special controls identified by FDA were appropriate to
mitigate the relevant risks to health for this use. FDA published a
proposed order in the Federal Register of June 19, 2013 (78 FR 36702)
(the 2013 proposed order). FDA received and has considered one comment
on the 2013 proposed order as discussed in section II of this document.
Therefore, FDA has met this requirement under section 513(e)(1) of the
FD&C Act.
B. Requirement for Premarket Approval Application
FDA is requiring PMAs for IABP 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 held a meeting of a device classification panel
described in section 513(b) of the FD&C Act with respect to IABP
devices on December 5, 2012. The 2012 Panel recommended that IABP
devices when indicated for septic shock or pulsatile flow generation
remain in class III (subject to premarket approval application). The
2012 Panel supported FDA's conclusion that the effectiveness of IABP
devices when indicated for septic shock or pulsatile flow generation
has not been established through adequate scientific evidence. FDA
published the 2013 proposed order on June 19, 2013 (78 FR 36702). FDA
received and has considered one comment on the 2013 proposed order as
discussed in section II of this document, 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. The 2013 proposed order satisfies these requirements.
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 IABP
devices, the preamendments class III devices that are the subject of
this final order, the later of these two time periods is the 90-day
period. Since these devices were classified in 1980, the 30-month
period has expired (45 FR 7966; February 5, 1980). Therefore, 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 this final order. If a
PMA is not filed for such device within 90 days after the issuance of
this final order, the device will be deemed adulterated under section
501(f) of the FD&C Act.
Also, a preamendments device subject to the order process under
section 515(b) of the FD&C Act is not required to have an approved
investigational device exemption (IDE) (see part 812 (21 CFR part 812))
contemporaneous with its interstate distribution until the date
identified by FDA in the final order requiring the filing of a PMA for
the device. At that time, an IDE is required only if a PMA has not been
filed. If the manufacturer, importer, or other sponsor of the device
submits an IDE application and FDA approves it, the device may be
distributed for investigational use. If a PMA is not filed by the later
of the two dates, and the device is not distributed for investigational
use under an IDE, the device is deemed to be adulterated within the
meaning of section 501(f)(1)(A) of the FD&C Act, and subject to seizure
and condemnation under section 304 of the FD&C Act (21 U.S.C. 334) if
its distribution continues. Other enforcement actions include, but are
not limited to, the following: Shipment of devices in interstate
commerce will be subject to injunction under section 302 of the FD&C
Act (21 U.S.C. 332) and the individuals responsible for such shipment
will be subject to prosecution under section 303 of the FD&C Act (21
U.S.C. 333). FDA
[[Page 79302]]
requests that manufacturers take action to prevent the further use of
devices for which no PMA has been filed.
II. Public Comments in Response to the Proposed Order
In response to the 2013 proposed order to reclassify IABP devices
when indicated for acute coronary syndrome, cardiac and non-cardiac
surgery, or complications of heart failure, and require the filing of a
PMA or a notice of completion of a PDP for IABP devices when indicated
for septic shock or pulsatile flow generation, FDA received one
comment. The comment supported FDA's intent to call for PMAs for IABP
devices when indicated for septic shock or pulsatile flow generation,
but disagreed with FDA's intent to reclassify IABP devices when
indicated for acute coronary syndrome, cardiac and non-cardiac surgery,
or complications of heart failure, stating that the risks to health are
``serious,'' and ``special controls are inadequate to provide
reasonable assurance of safety and effectiveness for these complex,
life-supporting devices.''
FDA disagrees with this comment. According to section 513(a)(1)(C)
of the FD&C Act, a class III device is defined as a device which (1)
``cannot be classified as a class I device because insufficient
information exists to determine that the application of general
controls are sufficient to provide reasonable assurance of the safety
and effectiveness of the device,'' and (2) ``cannot be classified as a
class II device because insufficient information exists to determine
that the special controls . . . would provide reasonable assurance of
its safety and effectiveness,'' and (3) ``is purported or represented
to be for a use in supporting or sustaining human life or for a use
which is of substantial importance in preventing impairment of human
health,'' or (4) ``presents a potential unreasonable risk of illness or
injury.'' Although FDA considers IABP devices to be life-supporting, a
viewpoint which was supported by the 2012 Panel, FDA believes that,
based on the available evidence, that special controls, in addition to
general controls, would be sufficient to provide a reasonable assurance
of safety and effectiveness, and there is not an unreasonable risk of
illness or injury for IABP devices when indicated for acute coronary
syndrome, cardiac and non-cardiac surgery, or complications of heart
failure. The 2012 Panel agreed with FDA's conclusions and provided the
following rationale for recommending that these devices 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. Therefore, FDA disagrees that
IABP devices when indicated for acute coronary syndrome, cardiac and
non-cardiac surgery, or complications of heart failure should be
classified as class III devices. FDA believes that the identified
special controls mitigate the risks to health and provide a reasonable
assurance of safety and effectiveness for this patient population with
high morbidity and mortality.
The commenter also provided a summary of recalls and adverse event
reports in FDA's Manufacturer and User Facility Device Experience
(MAUDE) database for this device type to support their perspective that
reclassification is inappropriate for IABP devices when indicated for
acute coronary syndrome, cardiac and non-cardiac surgery, or
complications of heart failure. FDA is aware of this data, fully
considered this information prior to the proposed reclassification, and
presented this information to the 2012 Panel. As such, this is not new
information which would have a bearing on FDA's decision to reclassify
IABP devices when indicated for acute coronary syndrome, cardiac and
non-cardiac surgery, or complications of heart failure from class III
to class II.
The commenter further notes that ``A major problem with this
proposed order is that it splits the device into two classifications
(Class III and Class II) . . . down-classification for any indication
would create an enormous and dangerous loophole that would allow
manufacturers to avoid the more rigorous PMA review process.'' FDA
disagrees with this comment. FDA does not regulate the practice of
medicine but rather regulates the use of a device as indicated by the
party offering the device for interstate commerce. The indications for
IABP devices are limited by the codified classification.
The commenter also states that ``the down-classification of these
devices means that companies manufacturing new models with unique
characteristics in the future would not be required to provide that
their products are safe or effective.'' The commenter suggests that
classification to class II (special controls) precludes FDA from
requesting clinical data for these devices. FDA disagrees with this
comment. FDA believes that the proposed special controls provide a
reasonable assurance of safety and effectiveness for IABP devices that
feature similar technology when indicated for acute coronary syndrome,
cardiac and non-cardiac surgery, or complications of heart failure. FDA
is also not precluded from requesting clinical data for IABP devices
where it is necessary to demonstrate substantial equivalence.
III. The Final Order
Under sections 513(e) and 515(b) of the FD&C Act, FDA is adopting
its findings as published in the preamble to the 2013 proposed order.
FDA is issuing this final order to require the filing of a PMA or a
notice of completion of a PDP for IABP devices when indicated for
septic shock or pulsatile flow generation. In addition, FDA is issuing
this final order to reclassify IABP devices when indicated for acute
coronary syndrome, cardiac and non-cardiac surgery, or complications of
heart failure from class III to class II and establish special
controls. This final order will revise part 870 (21 CFR part 870).
Under the final order, a PMA or a notice of completion of a PDP is
required to be filed on or before 90 days after the date of publication
of the final order in the Federal Register, for any of these class III
preamendments devices that were in commercial distribution before May
28, 1976, or that has been found by FDA to be substantially equivalent
to such a device on or before 90 days after the date of publication of
the final order in the Federal Register. An approved PMA or a declared
completed PDP is required to be in effect for any such devices on or
before 180 days after FDA files the application. Any other class III
preamendments device subject to this order that was not in commercial
distribution before May 28, 1976, is required to have an approved PMA
or a declared completed PDP in effect before it may be marketed.
If a PMA or a notice of completion of a PDP for any of the class
III preamendments devices is not filed on or before the 90th day past
the effective date of this regulation, that device will be deemed
adulterated under section 501(f)(1)(A) of the FD&C Act, and commercial
distribution of the device must cease immediately. The device may,
however, be distributed for investigational use, if the requirements of
the IDE regulations (part 812) are met.
Following the effective date of this final order, firms submitting
a 510(k) premarket notification for an IABP device when indicated for
acute coronary syndrome, cardiac and non-cardiac surgery, or
complications of
[[Page 79303]]
heart failure will need either to (1) comply with the particular
mitigation measures set forth in the codified special controls or (2)
use alternative mitigation measures, but demonstrate to the Agency's
satisfaction that those alternative measures identified by the firm
will provide at least an equivalent assurance of safety and
effectiveness.
Section 510(m) of the FD&C Act provides that FDA may exempt a class
II device from the premarket notification requirements under section
510(k) of the FD&C Act if FDA determines that premarket notification is
not necessary to provide reasonable assurance of the safety and
effectiveness of the devices. FDA has determined that premarket
notification is necessary to provide reasonable assurance of safety and
effectiveness of IABP devices when indicated for acute coronary
syndrome, cardiac and non-cardiac surgery, or complications of heart
failure, and therefore, this device type is not exempt from premarket
notification requirements.
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 this final order. 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 may present a risk to health is required
to submit a written report of the correction to FDA.
IV. 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.
V. Paperwork Reduction Act of 1995
This final order refers to previously approved collections of
information found in FDA regulations. These collections of information
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 812 have been approved under
OMB control number 0910-0078; the collections of information in 21 CFR
part 807, subpart E, have been approved under OMB control number 0910-
0120; the collections of information in 21 CFR part 814, subpart B,
have been approved under OMB control number 0910-0231; and the
collections of information under 21 CFR part 801 have been approved
under OMB control number 0910-0485.
VI. 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. Although sections 513(e) and 515(b) of the FD&C
Act as amended require FDA to issue final orders rather than
regulations, FDASIA also provides for FDA to revoke previously issued
regulations by order. FDA will continue to codify reclassifications and
requirements for approval of an application for premarket approval 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 final
order, we are revoking the requirements in Sec. 870.3535 related to
the classification of IABP devices when indicated for acute coronary
syndrome, cardiac and non-cardiac surgery, or complications of heart
failure as class III devices and codifying the reclassification of
these devices into class II.
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, 21 CFR part
870 is 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) 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
demonstrate mechanical integrity, durability, and reliability to
support its intended purpose; and
(vi) Labeling must include 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 the Food and
Drug Administration on or before March 31, 2014, 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 March 31, 2014, 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: December 23, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-31218 Filed 12-27-13; 8:45 am]
BILLING CODE 4160-01-P