[Federal Register Volume 80, Number 19 (Thursday, January 29, 2015)]
[Rules and Regulations]
[Pages 4783-4791]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-01619]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 870
[Docket No. FDA-2013-N-0234]
Effective Date of Requirement for Premarket Approval for
Automated External Defibrillator Systems
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
issuing a final order to require the filing of premarket approval
applications (PMA) for automated external defibrillator (AED) systems,
which consist of an AED and those AED accessories necessary for the AED
to detect and interpret an electrocardiogram and deliver an electrical
shock (e.g., pad electrodes, batteries, adapters, and hardware keys for
pediatric use).
DATES: This order is effective on January 29, 2015.
FOR FURTHER INFORMATION CONTACT: Linda Ricci, Center for Devices and
Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. 1314,
Silver Spring, MD 20993, 301-796-6325, [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 (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), among other amendments, established 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(d) of the FD&C Act (21 U.S.C. 360c(d)), 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 (21 U.S.C.
360c(f)) 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 (21 U.S.C. 360c(i)), 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 (both the preamendments and substantially
equivalent devices are referred to as preamendments class III devices)
may be marketed without submission of a premarket approval application
(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 (21 U.S.C. 360e(b)(1)) 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 product development protocol (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 (21 U.S.C. 360e(b)), this document will
refer only to the requirement for the filing and receiving approval of
a PMA.
On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA (126
Stat. 1056) amended section 513(e) of the FD&C Act (21 U.S.C. 360c(e)),
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 (21 U.S.C. 360e(b)) changing the mechanism for
requiring premarket approval for a preamendments class III device from
rulemaking to an administrative order.
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.
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.
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 AED systems,
the later of these two time periods is the 90-day period. Therefore,
section 501(f)(2)(B) of the FD&C Act (21 U.S.C. 351(f)(2)(B)) requires
that a PMA
[[Page 4784]]
for such devices be filed within 90 days of the effective date of a
final order. However, for the reasons discussed below, FDA does not
intend to enforce compliance with the 90-day deadline for PMA
submissions for currently marketed AEDs and those AED accessories
identified in 21 CFR 870.5310(a) (see further discussion in section V,
``Implementation Strategy'').
Also, a preamendments device subject to the order process under
section 515(b) of the FD&C Act (21 U.S.C. 360e) 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
(21 U.S.C. 351(f)(1)(A)), 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 may be
subject to injunction under section 302 of the FD&C Act (21 U.S.C.
332), and the individuals responsible for such shipment may be subject
to prosecution under section 303 of the FD&C Act (21 U.S.C. 333). FDA
requests that manufacturers take action to prevent the further use of
devices for which no PMA has been filed.
II. Regulatory History of This Device
On January 25, 2011, the Circulatory System Devices Panel
(``Panel'') recommended that AED systems be classified as class III
devices and subject to premarket approval to provide reasonable
assurance of the safety and effectiveness of the device (Ref. 1). The
Panel recommended that AED systems be regulated as class III devices
because, among other things, they are lifesaving devices. Furthermore,
the problems identified in adverse events in the medical device
reporting systems and recalls related to AED systems indicated these
devices require more regulatory oversight.
FDA published a proposed order to require PMAs for AED systems in
the Federal Register of March 25, 2013 (78 FR 17890). FDA is now
requiring PMAs for AED systems, which include AED accessories necessary
for the functionality of the AED (e.g., pad electrodes, batteries,
adapters, and hardware keys for pediatric use) (``necessary AED
accessories'') (see section IV, ``The Final Order'').
FDA received and has considered comments on the AED systems
proposed order as discussed in section III of this document.
III. Public Comments in Response to the Proposed Order
In response to the March 25, 2013 (78 FR 17890) proposed order to
maintain the class III classification and require premarket approval
for AED systems, FDA received 66 comments and one petition for
reclassification (see FDA-2013-N-0234-0002).\1\ The comments and the
FDA's responses to the comments are summarized below. Certain comments
are grouped together under a single number because the subject matter
of the comments is similar. The number assigned to each comment is
purely for organizational purposes and does not signify the comment's
value or importance or the order in which it was submitted.
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\1\ FDA will respond separately to the reclassification petition
and will address the issues raised in that petition in its response.
The reclassification petition is available at http://www.regulations.gov/#!documentDetail;D=FDA-2013-N-0234-0002.
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(Comment 1) Many comments indicated that AED systems have already
been demonstrated to be safe and effective, and referenced literature
and studies supporting the reliability of these devices and the value
of AED systems in treating sudden cardiac arrest (SCA). The comments
stated that PMAs and associated increased regulatory cost and review
time is not warranted and would hinder innovation, increase device cost
to consumers, and reduce availability of AED systems. The comments
further stated that it is widely recognized that improvement in the
survival rate from SCA is due in large part to widespread distribution
of AED systems and expressed concern that requiring PMAs would limit
availability of the devices.
(Response 1) FDA agrees that many currently marketed AEDs have been
demonstrated to be effective in clinical use and, when designed and
manufactured appropriately, AEDs can be safe and effective. However,
FDA believes that there is insufficient information to determine that
general and special controls would provide a reasonable assurance of
the safety and effectiveness of these devices, which are for a use in
supporting or sustaining human life (see section 513(a)(1)(C) of the
FD&C Act (21 U.S.C. 360c(a)(1)(C))). Specifically, the postmarket
information on AEDs supports increased regulatory review to ensure that
device design and manufacturing practices provide a reasonable
assurance of safety and effectiveness. FDA acknowledges that the PMA
process may result in increased regulatory cost to manufacturers;
however, FDA believes that device quality will improve, which will
reduce costs associated with postmarket actions including recalls.
FDA also agrees that continued efforts to make safe and effective
AED systems available is in the interest of public health, but
disagrees that this call for PMAs will limit device availability. FDA
believes that many manufacturers of currently marketed AEDs already
have, or can reasonably obtain, the necessary data to support a PMA,
and hence expects AED distribution to continue to meet demand. Also,
for the reasons discussed below, FDA does not intend to enforce
compliance with the 90-day deadline for submission of PMAs for
currently marketed AEDs and necessary AED accessories (for further
discussion see section V, ``Implementation Strategy'').
At the January 2011 Panel meeting, the Panel discussed the impact
of FDA regulatory scrutiny on innovation. Various Panel members agreed
that the appropriate focus should be on assuring reliability of AEDs
and that there was no evidence presented to indicate that a call for
PMAs would unduly hinder device innovation (Ref. 1). FDA notes that
previous significant innovations for AED systems (e.g., new
defibrillation waveforms) have been supported by clinical evidence in
the 510(k) process and that under the PMA process this clinical
evidence is not expected to significantly change. As was mentioned in
the proposed order, FDA anticipates that many AED manufacturers already
have sufficient clinical evidence to support a PMA.
(Comment 2) Several comments noted that AED system failures are
often the result of use error or improper maintenance (e.g., expired
batteries/pads, periodic checks not performed, etc.) and not of system
failure or malfunction. The comments stated that efforts should be
devoted to ensuring appropriate public awareness, training
(particularly for lay users), and maintenance to address these issues
as opposed to increasing premarket regulatory review. One comment
stated that the proposed order should not be finalized until all
stakeholders, not only device manufacturers, are engaged in an
[[Page 4785]]
integrated approach to increase the likelihood that AED systems will be
available and functional when needed.
(Response 2) FDA agrees that AED system training and maintenance
are important to help ensure AED system availability and proper use and
also believes manufacturers and users are in the best position to
develop and implement training and maintenance materials. FDA supports
ongoing discussions and efforts to improve training and maintenance,
but disagrees that these activities should delay finalizing the
requirement for PMAs for these devices. Although we recognize that
there have been some medical device reports (MDRs) associated with use
errors, the focus of FDA's review of MDRs and recalls of AED systems
has been related to problems with the quality of these devices as
related to device design and manufacture and FDA continues to believe
that requiring PMAs is appropriate.
(Comment 3) Several comments stated that special controls,
including performance testing to industry standards, device labeling,
guidance documents, human factors analysis and design, summary of field
actions and mitigations to address Quality System (QS) concerns, risk
management, and post-market surveillance were sufficient to regulate
AED systems as class II devices under the existing 510(k) regulatory
regime. One comment indicated that several of the regulatory controls
identified by FDA as consistent with PMA requirements--such as pre-
market inspections, review of changes that could significantly affect
the safety or effectiveness of the device, and postmarket
surveillance--could also be conducted under the 510(k) regime. Other
comments supported FDA's proposal to maintain the devices in class III
and agreed that the manufacturing controls, premarket review
requirements, and assessment of lay use are best managed under the PMA
process.
(Response 3) FDA disagrees that there is sufficient information to
determine that general and special controls would provide a reasonable
assurance of safety and effectiveness of these devices given safety
concerns related to the manufacturing processes and design changes,
problems which FDA considered in determining that PMAs are warranted
(see section 513(a)(1)(C) of the FD&C Act (21 U.S.C. 360c(a)(1)(C))).
FDA does not generally conduct preclearance inspections under the
510(k) process because such information is not required in a 510(k)
submission under the FD&C Act or FDA regulations. Further, under
section 513(f)(5) of the FD&C Act (21 U.S.C. 360c(f)(5)), FDA may not
withhold a 510(k) ``because of a failure to comply with any provision
of this Act unrelated to a substantial equivalence decision, including
a finding that the facility in which the device is manufactured is not
in compliance with good manufacturing requirements as set forth in
regulations of the Secretary under section 520(f) (other than a finding
that there is a substantial likelihood that the failure to comply with
such regulations will potentially present a serious risk to human
health).'' In contrast, under section 515(c)(1)(C) of the FD&C Act (21
U.S.C. 360e(c)(1)(C)), a PMA must include ``a full description of the
methods used in, and the facilities and controls used for, the
manufacturing, processing, and when relevant, packing and installation
of, such device.'' Moreover, many of the design and manufacturing
changes that have led to AED system recalls were not required to be
reported to FDA under the 510(k) process. If these changes had been
reported prior to implementation, as would be required in the PMA
regime, these recalls may have been avoided. FDA continues to believe
that the necessary regulatory controls for AED systems are consistent
with the PMA review process, and that the 510(k) process does not
provide sufficient regulatory oversight for these devices.
Similarly, FDA's oversight of postmarket changes to devices is very
different in the 510(k) context as compared to the PMA context. Under
21 CFR 807.81, FDA requires 510(k)s for a change to a device only when
the change ``could significantly affect the safety or effectiveness of
the device, e.g., a significant change or modification in design,
material, chemical composition, energy source, or manufacturing
process. '' In contrast, under 21 CFR 814.39, FDA requires PMA
supplements (including 30-day notices) for any change to a PMA-approved
device that affects safety or effectiveness. These differences in
authorities, among the other reasons discussed above, warrant
regulation of AEDs in class III.
(Comment 4) A few comments indicated that existing AED and AED
accessory manufacturers are already subject to the QS regulation (21
CFR 820) and manufacturing quality would not be measurably improved as
a result of requiring PMAs. One comment noted that specific
expectations under the QS regulation for design controls, purchasing
controls, and other issues identified by FDA as problematic for AEDs
could be addressed by special controls and other regulations, and AEDs
could remain in class II. One comment further stated that such concerns
could be managed via postmarket controls, which are available under the
510(k) regime, such as submission of a summary of recent field actions
and related design mitigations.
(Response 4) FDA disagrees with the comments. FDA acknowledges that
AED and AED accessory manufacturers are already subject to the QS
regulation and that QS requirements result in rigorously designed and
manufactured devices and resultant quality improvements. By requiring
premarket review of QS processes as well as device changes for AEDs,
FDA believes the PMA process will provide a reasonable assurance of
safety and effectiveness (see Response 3 above).
(Comment 5) One comment stated that certain AED accessories,
specifically electrodes, cables, and adapters, are well-understood
devices and that their classification into class III is not warranted.
The comment stated that these accessories could be adequately regulated
in class II with special controls, as is already the case when these
accessories are used with manual defibrillators. The comment
recommended special controls, including the following: Performance
testing, usability evaluation, labeling, biocompatibility, and
readiness for use. Two comments stated that because AED accessories
often have identical designs and the same intended use as accessories
used with class II manual defibrillators, FDA should not perform
duplicative reviews under both the 510(k) and PMA regimes and that PMA
review should be required only when use of the accessory with an AED
results in a change in intended use or design.
(Response 5) Accessories necessary for an AED to detect and
interpret an electrocardiogram and deliver an electrical shock (e.g.,
battery, pad electrode, adapter, and hardware keys for pediatric use)
are necessary for AED system functionality. Failure of these necessary
accessories leads to the same negative outcomes as a failure of the AED
itself; e.g., an AED not ready for use because of a faulty battery is
unable to detect heart rhythm abnormalities and/or deliver a
defibrillation shock to a victim of SCA. FDA's review of adverse events
and recalls has shown that problems with AED accessories have occurred
during clinical use. As such, FDA continues to believe that the same
regulatory oversight is warranted for certain critical accessories
(i.e., batteries, pad electrodes, adapters, and hardware keys for
pediatric use) as for the AEDs with which they are used. As discussed
in the response to Comment 3 above, FDA does not believe that
[[Page 4786]]
adequate regulatory controls are available under the 510(k) process,
and hence PMAs are necessary to provide a reasonable assurance of
safety and effectiveness.
(Comment 6) Several comments questioned the validity of FDA's data
regarding adverse events associated with AED failures. One comment
noted that FDA provided no data in the proposed order on the frequency
of adverse events or relationship of number of events to total
distribution and use of AEDs. The comment requested additional
information from FDA to support the validity of the MDR analysis
presented at the 2011 Panel and relied upon to support the proposed
order. A few comments presented alternate analyses of MDR data that
suggested that MDRs for AEDs are not increasing. One comment presented
an analysis that showed no statistically significant increase in the
rate of adverse event reports over the time period of 2007 to 2011. Two
comments stated that a majority of AED MDRs reported to FDA resulted
from self-test errors--which are reported as malfunction MDRs because
they could cause or contribute to a death or serious injury but do not
represent device failures in clinical use. The comments contended that
any analysis of MDRs should focus instead on actual use adverse events,
which would represent a small subset of the overall MDRs. One comment
stated that self-test related events are representative of an effective
design risk mitigation strategy being employed for AEDs and that
because AEDs are often in standby for a large percentage of time, self-
test detection of problems before use should not be included in the
overall assessment of the benefit-risk profile for AEDs. Two comments
requested further guidance from FDA on MDR reporting expectations for
AEDs.
(Response 6) Although FDA requires manufacturers to submit an MDR
when their device may have caused or contributed to a death, serious
injury, or in certain situations when their device has malfunctioned,
FDA acknowledges that there are limitations on the review of MDR data,
including the fact that FDA typically does not have complete
information on the number of devices in distribution from which to
calculate adverse events rates. These limitations were discussed at the
2011 Panel meeting. FDA has previously stated that fatality statistics
and injury statistics from MDRs should be considered in light of
underreporting (58 FR 61952 at 61972, November 23, 1993). In addition,
FDA notes that the evaluation of MDR data for AEDs was focused on
manufacturing and design concerns and was not aimed at developing
specific failure rates. Moreover, FDA believes that the large number of
devices in distribution and the life-saving nature of these devices
combined with the steady rate of MDRs support a call for PMAs to help
ensure that these devices are adequately designed and manufactured so
that they are available when needed.
FDA disagrees that evaluation of adverse events should focus only
on those events that occur during clinical use. Although some
distributed AEDs may seldom be used, this does not reduce the
importance that they are safe and effective when needed. FDA
acknowledges the importance of AED self-test features and recognizes
that many self-test failures are not indicative of issues with overall
device quality. FDA believes, however, that some self-test failures
signal significant quality problems arising from device design or
manufacturing issues and are appropriately considered as adverse events
if recurrence of such failures could, for example, render the device
unavailable for use when needed. FDA also recognizes that some MDRs may
eventually be found to be the result of problems not associated with
the device; however, this concern is applicable to all devices subject
to adverse event reporting requirements and FDA does not believe such
reports unduly influence overall reporting numbers.
FDA also notes that our review of available information, as
presented at the January 2011 Panel meeting, included data on voluntary
corrections and removals (i.e., ``recalls'') of AEDs pursuant to
section 519(g) of the FD&C Act (21 U.S.C. 360i(g)). Recalls are
conducted ``(A) to reduce a risk to health posed by the device, or (B)
to remedy a violation of this Act caused by the device which may
present a risk to health,'' and as such may reflect safety concerns for
AEDs (section 519(g)(1) of FD&C Act (21 U.S.C. 360i(g)(1)). Since the
January 2011 Panel meeting, over 40 additional class I or class II
recalls have been conducted by AED manufacturers and have impacted over
2 million distributed AEDs (Ref. 2). The root cause of these recalls
has been attributed to a variety of causes, with design controls,
purchasing controls, and receiving acceptance activities being the most
common. FDA continues to believe that the recall data reinforces the
overall conclusion regarding the inadequacy of regulatory controls for
AED systems under the 510(k) process.
Additional guidance on MDR requirements for AEDs is beyond the
scope of this document; however, FDA intends to continue efforts to
clarify medical device reporting expectations and manufacturers who
have questions regarding their reporting obligations should contact
FDA.
(Comment 7) Several comments responded to FDA's request for
feedback regarding whether 15 months is sufficient to allow companies
to collect information necessary to support submission of a PMA. Two
comments stated that this issue was dependent on the data expected by
FDA and that FDA should provide more guidance in this respect. One
comment requested clarification on what clinical data is known to FDA
that would support a PMA because it is critical that AED manufacturers
understand the type and amount of data that will be required. One
comment stated that it is unclear what FDA's expectations would be for
clinical trials of new AEDs or the need for clinical trials for AED
accessories given available less burdensome methods for obtaining
performance data on accessories. Another comment requested
clarification on whether AED manufacturers would be expected to re-test
and re-validate older AED models to currently recognized standards. One
comment requested clarification on when marketing materials for AEDs
would need to comply with 21 CFR 801.109.
One comment suggested that the 15-month period should be extended
to 30 months, which the commenter claimed would be consistent with
section 501(f)(2)(B) of the FD&C Act (21 U.S.C. 351(f)(2)(B). One
commenter requested clarification regarding whether the 15 months
started at the 90th day after a final order was issued and another
comment indicated that 15 months should be sufficient, but that the 15
months should not include FDA's 180-day PMA review time. One comment
suggested that FDA require PMAs 90 days after the final order.
(Response 7) The data required to support premarket approval will
vary by device and the specific data requirements. FDA is aware of
clinical study information that can be leveraged for AEDs from both
published studies and clinical data previously submitted to FDA under
the 510(k) process, and, as was stated in the proposed order, FDA
believes that many AED accessories ``may need to submit non-clinical
performance testing with confirmatory animal studies in order to
support independent PMA approval'' (78 FR 17894, March 25, 2013).
Performance testing of AEDs must be provided in a PMA to support a
reasonable assurance of safety and effectiveness. Although retesting
older
[[Page 4787]]
AED models to currently recognized standards is one way to meet the
performance testing requirements, compliance with such standards is
voluntary and manufacturers may submit a justification for how other
testing conducted on their devices provides equivalent assurances of
safety and effectiveness. FDA encourages manufacturers to proactively
engage FDA via the pre-submission process to discuss the specific data
needed for their PMAs (Ref. 3). FDA notes that existing prescription
AEDs are already subject to 21 CFR 801.109, and will remain so after
this call for PMAs. FDA review of AED PMAs will include review of the
associated AED labeling to ensure such device labeling complies with
regulatory requirements.
FDA notes that the 30 months discussed in section 501(f)(2)(B) of
the FD&C Act (21 U.S.C. 351(f)(2)(B)) references the date from initial
classification of a device into class III. AEDs have been classified as
class III for more than 30 months, and hence this statutory provision
has expired. FDA also acknowledges that it is in the interest of public
health to ensure the availability of AEDs because they are life-saving
devices and their clinical use is well-established. After consideration
of the comments, FDA continues to believe that the proposed 15 months
for filing a PMA (Ref. 4) strikes an appropriate balance between the
need to ensure continued availability of AEDs for the public health
reasons stated above and the implementation of PMA requirements to
ensure the safety and effectiveness of AEDs.
For currently marketed AEDs, FDA does not intend to enforce
compliance with the 90-day deadline by which PMAs must be submitted for
15 months after that deadline (i.e., 18 months after the effective date
of the final order), as long as a notice of intent to file a PMA is
submitted within 90 days of the effective date of the final order (see
section V, ``Implementation Strategy''). Even if a notice of intent and
PMA are submitted by these dates, manufacturers must cease distribution
of devices upon receiving a not approvable or denial decision rendered
on a PMA. To resume distribution, these manufacturers must receive PMA
approval for their devices.
Moreover, for currently marketed necessary AED accessories, FDA
does not intend to enforce compliance with the 90-day deadline by which
PMAs must be submitted for 57 months after that deadline (i.e., 5 years
after the effective date of the final order) (see section V,
``Implementation Strategy''). Continued availability of necessary AED
accessories, including consumable accessory items (e.g., pad
electrodes) and accessories with limited useful life (e.g., batteries),
is critical to ensuring the safety and efficacy of currently marketed
AEDs during the time while PMAs for those AEDs are being pursued. In
addition, the continued availability of necessary accessories for
``legacy devices''--individual AEDs that have been distributed and are
currently in use (e.g., in public facilities, etc.) and for which the
manufacturer is not seeking PMA approval for that AED model--ensures
the availability of functional legacy AEDs until they are replaced with
PMA-approved AEDs.
(Comment 8) One commenter stated that FDA did not have a legal
basis for continuing with finalization of a call for PMAs for AED
systems because FDA failed to convene a panel as is required under
FDASIA prior to issuing a final order. The commenter stated that FDA
may not rely on the 2011 pre-FDASIA Panel because that Panel meeting
was related to reclassifications under section 515(i) of the FD&C Act
(21 U.S.C. 360e(i)) and not related to calls for PMAs under section
515(b) of the FD&C Act (21 U.S.C. 360e(b)). The commenter further
contended that the 2011 Panel neither considered new information
contained in a reclassification petition submitted to FDA in 2009 nor
adequately discussed the appropriateness of class II special controls.
(Response 8) FDA disagrees with the comment that FDA does not have
a legal basis to finalize an order calling for PMAs for AED systems.
Pursuant to FDASIA, the amendments to section 515(b) of the FD&C Act
require, in relevant part, that issuance of an administrative order
calling for PMAs for a preamendments device be preceded by a proposed
order and a meeting of a classification panel. As amended, this section
of the FD&C Act does not prescribe when these two events (the panel and
proposed order) must occur in relation to each other. More importantly,
FDA believes that the Panel's deliberations and recommendations remain
relevant and fully satisfy the requirements in section 515(b) of FD&C
Act.
FDA disagrees with the comment that the Panel did not consider new
information contained in the 2009 reclassification petition. A
representative from the petitioner was present at the meeting and
provided comments on the reclassification petition during the Panel
meeting (Ref. 1). In addition, the petitioner was given an opportunity
to explain the petitioner's reasons for why AEDs should be class II
devices, including a discussion of the special controls described in
the reclassification petition. Therefore, the Panel heard the
petitioner's arguments and these arguments were available for the
Panel's consideration when it made its recommendation.
(Comment 9) One commenter objected to FDA's use of the term
``diagnose'' in the proposed order to describe the functionality of
AEDs (78 FR 17893, March 25, 2013), and stated that AEDs sense
shockable rhythms and are not diagnostic devices.
(Response 9) FDA disagrees that these devices do not perform
diagnostic functions. AEDs analyze and interpret ECG data to produce an
assessment as to whether a shock should be delivered; while FDA does
believe that AEDs have diagnostic functions, we note that the
regulatory identification for the device in 21 CFR 870.5310(a), as
finalized in the order, does not use the term diagnose, and instead
describes the function of the device as ``analyzes'' and
``interprets.''
(Comment 10) One commenter stated that FDA's proposal to allow
manufacturers to ``bundle'' several AED models under a single PMA is
inconsistent with the PMA regulatory paradigm, which relies on a
device-by-device assessment. The comment points to FDA's guidance on
bundling, which states that ``[g]enerally, [manufacturers] should not
bundle differing generic device types in a single PMA submission
because of the substantially different pre-clinical and clinical data
needed to support each of the devices'' (Ref. 5).
(Response 10) FDA disagrees with the comment. Different AED models
can be included in one PMA if they are the same generic device type.
Because shock advisory algorithms and defibrillation waveforms will
likely be common across various models from a given manufacturer of
devices, FDA expects the clinical data needed to support devices within
an appropriately bundled AED PMA to be the same. However, because of
the differences in device labeling and user requirements between
professional and lay use devices, FDA continues to believe that
separate PMAs should be submitted for a manufacturer's professional use
versus lay use devices. FDA believes this approach is least burdensome
to manufacturers and is consistent with the bundling guidance, which
states that ``[b]undling is appropriate for devices that present
scientific and regulatory issues that can most efficiently be addressed
during one review'' (Ref. 5).
(Comment 11) One comment requested clarification on whether
[[Page 4788]]
separate PMAs are required for AEDs and the associated AED accessories
when a company manufacturers both for use together. Two comments
requested additional clarification on whether accessories not specified
in the proposed order (such as electrocardiograph modules and
electrodes, training pads/batteries, protective carrying cases,
Bluetooth modules, hardware keys or specialized pads to reduce energy
for pediatric use, self-testers, SpO2/blood pressure
monitoring devices, cardiopulmonary resuscitation (CPR) aids, medical
device data systems (MDDS), etc.) would require PMAs. One comment
suggested that AED accessories that are already 510(k) cleared should
not be subject to premarket approval by virtue of being used with an
AED.
(Response 11) In response to this comment, FDA has revised the
identification language to clarify that AED accessories regulated under
21 CFR 870.5310 are ``those accessories necessary for the AED to detect
and interpret an electrocardiogram and deliver an electrical shock
(e.g., battery, pad electrode, adapter, and hardware keys for pediatric
use).'' Manufacturers of accessory devices that are not addressed by
the final order and are not already the subject of an existing
classification regulation should contact FDA.
Under the final order, manufacturers must submit PMAs for
accessories that are necessary for operation of the AED system (e.g.,
accessories necessary to allow the AED to detect or interpret an
electrocardiogram or deliver a defibrillation shock). These AED
accessories include batteries, pad electrodes (including reduced energy
pads for pediatric use), adapters, and hardware keys for pediatric use.
In response to this comment, FDA has added ``hardware keys for
pediatric use'' to the identification. Necessary AED accessories that
are for use with a specific AED should be included in that PMA for the
AED system as a whole. Alternatively, necessary AED accessories,
including those manufactured by a third party, may be submitted in
their own PMAs.
Accessories that are not necessary for the functionality of the AED
are not addressed by the final order. Currently marketed AED
accessories that are not addressed by the final order, such as
SpO2/blood pressure monitoring devices, ECG modules and
testers, CPR aids, and MDDS, may be subject to other regulations and
will continue to be subject to those existing regulations. Training
accessories such as training pads and batteries for training-only AEDs
are not currently subject to any additional regulations, and will not
become so as a result of the final order.
(Comment 12) One comment requested clarification regarding AEDs
being considered adulterated 90 days after the effective date of a
final order in the absence of submission of a statement of intent to
submit a PMA or the submission of a full PMA. The comment questioned
whether devices legally distributed prior to the 90th day could remain
in distribution. Another comment requested clarification on whether
manufacturers could continue to provide consumable accessory items
(such as batteries and pads) for previously distributed devices even if
a PMA will not be submitted for that AED model. Two comments requested
clarification on how and whether manufacturers would be allowed to
distribute components required for field servicing of a device,
including refurbished replacement devices, before PMAs are submitted
for the devices.
(Response 12) Under the final order (see section IV, ``the Final
Order'') and section 501(f)(2)(B) of the FD&C Act, PMAs must be
submitted within 90 days after the effective date of the final order
for currently marketed AED systems. If a PMA is not submitted, the
devices are adulterated. However, for the reasons discussed above, for
currently marketed AEDs, FDA does not intend to enforce compliance with
the 90-day deadline by which PMAs must be submitted for 15 months after
that deadline (i.e., 18 months after the effective date of the final
order), as long as a notice of intent to file a PMA is submitted within
90 days of the effective date of the final order (see section V,
``Implementation Strategy''). For currently marketed necessary AED
accessories, FDA also does not intend to enforce compliance with the
90-day deadline by which PMAs must be submitted for 57 months after
that deadline (i.e., 5 years after the effective date of the final
order) (see section V, ``Implementation Strategy). This intention
applies to necessary AED accessories regardless of whether a PMA is
being or has been sought for the AED model.
(Comment 13) One comment indicated that premarket review of medical
devices such as AEDs should include review of the software embedded
into the devices, including review of software verification and
validation documentation. The comment noted that such review should
also occur for software modifications and software developed for
maintenance of the devices, including self-test functions. The comment
relayed the importance of having reviewers with adequate training,
expertise, and experience.
(Response 13) FDA agrees with the comment. Review of AEDs under the
510(k) process has included a detailed review of software documentation
supporting premarket submissions by appropriately trained and
experienced FDA reviewers. The PMA review will also involve a review of
software documentation and will be conducted by trained and experienced
FDA reviewers.
(Comment 14) One comment suggested an alternative regulatory
approach whereby AEDs for medical professional use be reclassified into
class II and public access defibrillators used by laypersons remain in
class III with PMAs required. The comment stated that professional use
devices have advanced functionality and are operated by skilled and
trained professionals, which lessens the chance of human factor errors
and increases the likelihood that the user will be able to recognize
and troubleshoot any malfunctions. The comment stated that such users
can rely on past experience and other means of attempting to rescue a
patient, whereas lay users are often fully reliant on the AED. Two
comments also indicated that professional use devices are typically
manual defibrillators with additional functionality, including AED, and
that the proposed order would create an inconsistent system whereby the
same hardware if used only for manual defibrillation would be class II,
but by virtue of configuring the device to include AED functionality
would become a PMA class III product.
(Response 14) FDA disagrees with the comments and believes that the
submission of PMAs is warranted regardless of the intended user of the
device. FDA does not believe that there is sufficient information to
establish special controls to provide a reasonable assurance of safety
and effectiveness of the device regardless of the training of AED
users.
FDA recognizes that some manual defibrillators and AEDs share
common hardware and software platforms, and hence devices with similar
or identical platforms may receive different regulatory review based on
the configuration. For the reasons previously stated, however, FDA
continues to believe AED systems should be class III devices. FDA also
notes that the performance and other data needed to support safety and
effectiveness for hardware and software platforms for both types of
devices would be nearly identical; the difference would be related to
the amount of
[[Page 4789]]
information that must be submitted to FDA. For a PMA, more information
on the design controls process is required to be submitted whereas for
a 510(k) submission, some information may not need to be submitted and
instead can reside within the company's overall quality system and
associated design documentation. Such situations of different
regulatory processes have occurred in other product areas including
contact lenses (daily-wear are typically class II, whereas extended
wear are class III) and ablation devices (general surgical use are
class II, whereas use for treatment of atrial fibrillation is class
III), and FDA does not believe this changes the overall rationale
supporting the need for PMAs.
(Comment 15) Two comments noted that there are numerous companies
that refurbish and/or resell AEDs. The comments requested that FDA
include AED resellers and refurbishers in their consideration of
regulatory strategy.
(Response 15) Regardless of the supplier, the introduction or
delivery for introduction into interstate commerce of any device that
is adulterated is a prohibited act under section 301 of the FD&C Act
(21 U.S.C. 331) (see Comment 12). FDA encourages refurbishers and
resellers who have questions about the continued distribution of AEDs
to contact FDA via the pre-submission process.
(Comment 16) One comment requested clarification of the process for
modifications of currently marketed AEDs (and notifying FDA of such
modifications) during the 90-day period after the final order is
issued. One comment stated that given the nature of commercial,
electrical and mechanical components used in AEDs, an extended
transition period without the ability to implement changes would not be
tenable and would result in unavailability of devices. One comment
requested clarification on 510(k) submissions accepted for review, but
for which no decision had been rendered, prior to the effective date of
a final order calling for PMAs.
(Response 16) Under 21 CFR 870.5310, as amended, all new AED and
necessary AED accessories must have an approved PMA in effect before
being placed in commercial distribution. We recommend that
manufacturers of currently marketed AEDs contact FDA regarding
implementation of any changes necessary for their AEDs in order to
address safety concerns or to support ongoing distribution while PMA
approval is being sought. FDA understands that issues may arise
relating to part obsolescence or changes necessary to reduce a risk to
health posed by a currently marketed AED that is not functioning
properly.
All other changes need to be accounted for in a PMA. Moreover, all
new AED and necessary AED accessories must have an approved PMA in
effect before being placed in commercial distribution.
(Comment 17) One comment objected to the comparisons made by FDA at
the 2011 Panel meeting between implanted cardioverter defibrillators
(ICDs) (PMA devices) and AEDs. The comment noted the number of
commercial components (e.g., components supplied to multiple industries
for a variety of uses) in order to maintain affordable price-points for
AEDs and the potentially burdensome PMA supplements that would be
necessary to support incremental changes in manufacturing for AEDs. The
comment further contended that purchased component-related recalls for
AEDs have largely been a result of latent component failures and that
FDA's examples at the 2011 Panel meeting of QS concerns related to
changes to purchased components or device design would not have been
averted by the stricter premarket regulatory oversight via PMA
supplements.
(Response 17) FDA acknowledges that more stringent regulatory
oversight via the PMA process may not completely eliminate AED recalls.
FDA also recognizes that AEDs typically contain commercial components
and manufacturers will need to submit PMA supplements for changes to
these components, as well as changes to suppliers and manufacturing
processes. Use of commercial components in PMA devices is not uncommon
and changes at the component level may have led to some AED recalls and
adverse events, providing further support for increased regulatory
review. FDA continues to believe that these failures and the need for
careful consideration and adequate verification and validation of such
changes support more rigorous review under the PMA process.
(Comment 18) One comment requested clarification on activities
during the time after a notice of intent to file is submitted,
including whether FDA will place additional postmarket approval
requirements on previously distributed products as allowed under 21 CFR
814.82. The comment further asked whether IDEs would be required for
design changes (e.g., would an IDE be required to conduct human
factors/usability studies).
(Response 18) FDA will consider the need for postapproval
requirements in the context of each manufacturer's PMA submission and
the devices in distribution. FDA does not intend to exempt
manufacturers from the IDE requirements and hence any study which meets
the IDE requirements must be conducted in accordance with the
requirements of 21 CFR parts 50 and 812. There will be no extended
period for filing an IDE and studies may not be initiated without
appropriate IDE approvals. Manufacturers who have questions regarding
whether an IDE is needed for a particular AED study are encouraged to
interact with FDA via the pre-submission process.
IV. The Final Order
FDA is adopting its findings as published in the preamble of the
proposed order (78 FR 17890, March 25, 2013) and issuing this final
order to require the filing of a PMA for AED systems under 515(b) of
the FD&C Act (21 U.S.C. 360e(b)). An AED system consists of an AED and
those accessories necessary for the AED to detect and interpret an
electrocardiogram and deliver an electrical shock (e.g., battery, pad
electrode, adapter, and hardware keys for pediatric use). An AED system
analyzes the patient's electrocardiogram, interprets the cardiac
rhythm, and automatically delivers an electrical shock (fully automated
AED), or advises the user to deliver the shock (semi-automated or shock
advisory AED) to treat ventricular fibrillation or pulseless
ventricular tachycardia. Under section 515(b)(1)(A) of the FD&C Act (21
U.S.C. 360e(b)(1)(A)), PMAs for AED systems are required to be filed on
or before 90 days after the effective date of a final order. This final
order will revise 21 CFR part 870.
V. Implementation Strategy
Based on comments on the proposed order, we are clarifying FDA's
intentions regarding enforcing compliance with the final order (see
section IV, ``The Final Order'') and section 501(f)(2)(B) of the FD&C
Act (21 U.S.C. 351(f)(2)(B)).
A. Currently Marketed AEDs
Under the final order and section 501(f)(2)(B) (21 U.S.C.
351(f)(2)(B)), PMAs for currently marketed AEDs are required to be
filed on or before 90 days after the effective date of a final order.
However, for currently marketed AEDs, FDA does not intend to enforce
compliance with this 90-day deadline for 15 months after that deadline
(i.e., 18 months after the effective date of the final order), as long
as notice of intent to file a PMA is submitted within 90 days of the
effective date of the final order. The notification of the intent to
file a PMA submission must include a
[[Page 4790]]
list of all model numbers for which a manufacturer plans to seek
marketing approval through a PMA.
In conducting any clinical studies, AEDs may be distributed for
investigational use if the requirements of the IDE regulations (21 CFR
part 812) are met. There will be no extended period for filing an IDE
nor exemption from IDE requirements, and studies may not be initiated
without appropriate IDE approvals, where necessary.
B. Currently Marketed Necessary AED Accessories
Under the final order and section 501(f)(2)(B) (21 U.S.C.
351(f)(2)(B)), PMAs for currently marketed necessary AED accessories
are required to be filed on or before 90 days after the effective date
of this final order. However, for currently marketed necessary AED
accessories, FDA does not intend to enforce compliance with this 90-day
deadline for 57 months after the deadline (i.e., 5 years after the
effective date of the final order). Currently marketed necessary AED
accessory manufacturers are not required to file an intent-to-file by
the 90-day deadline.
After the effective date of the final order, new AEDs and necessary
AED accessories must have approved PMAs to be legally marketed. The
following tables show the regulatory timetable for currently marketed
AEDs and necessary AED accessories.
Table 1--Currently Marketed AEDs
----------------------------------------------------------------------------------------------------------------
Timetable for which FDA does
not intend to enforce Distribution period (time after
compliance (time after effective date of order)
effective date of order)
----------------------------------------------------------------------------------------------------------------
Intent to File a PMA.................. 90 days....................... Devices included in an intent to file:
18 months.
Devices not included in intent to file:
90 days.
File a PMA............................ 18 months..................... Until a not approvable decision or
denial decision is issued; can continue
distribution if an approval order is
issued.
----------------------------------------------------------------------------------------------------------------
Table 2--Currently Marketed Necessary AED Accessories
----------------------------------------------------------------------------------------------------------------
Timetable for which FDA does
not intend to enforce Distribution period (time after
compliance (time after effective date of order)
effective date of order)
----------------------------------------------------------------------------------------------------------------
Intent to File a PMA.................. N/A........................... N/A.
File a PMA............................ 60 months..................... Until a not approvable decision or
denial decision is issued; can continue
distribution if an approval order is
issued.
----------------------------------------------------------------------------------------------------------------
VI. Environmental Impact
The Agency has determined under 21 CFR 25.30 (h) 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.
VII. Paperwork Reduction Act of 1995
The 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.
VIII. Codification of Orders
Prior to the amendments by FDASIA, section 515(b) of the FD&C Act
(21 U.S.C. 360e(b)) provided for FDA to issue regulations to require
PMA approval for preamendments devices or devices found substantially
equivalent to preamendments devices. Section 515(b) of the FD&C Act (21
U.S.C. 360e(b)), as amended by FDASIA, provides for FDA to require PMA
approval for such devices by issuing a final order, following the
issuance of a proposed order in the Federal Register. FDA will continue
to codify the requirement for a PMA approval in the Code of Federal
Regulations. Therefore, under section 515(b)(1)(A) of the FD&C Act (21
U.S.C. 360e(b)(1)(A)), as amended by FDASIA, in this final order, we
are requiring PMA approval for AED systems and we are making the
language in 21 CFR 870.5310 consistent with the final version of this
order.
IX. 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.
(FDA has verified the Web site address, but FDA is not responsible for
any subsequent changes to the Web site after this document publishes in
the Federal Register.)
1. Meeting Materials for 515(i) Regulatory Classification of
Automated External Defibrillator Systems, January 25, 2011,
available at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm240575.htm.
2. U.S. Food and Drug Administration, Medical Device Recalls
Database, available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm.
3. Requests for Feedback on Medical Device Submissions: The Pre-
Submission Program and Meetings with Food and Drug Administration
Staff, Guidance for Industry and Food and Drug Administration Staff,
February 18, 2014, available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176.pdf.
4. Acceptance and Filing Reviews for Premarket Approval
Applications (PMAs), Guidance for Industry and Food and Drug
Administration Staff, December 31, 2012, available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM313368.pdf.
5. Guidance for Industry and FDA Staff: Bundling Multiple
Devices or Multiple Indications in a Single Submission, June 22,
2007, available at http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm089731.htm.
[[Page 4791]]
List of Subjects in 21 CFR Part 870
Medical 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. Section 870.5310 is amended by revising the section heading and
paragraphs (a) and (c) to read as follows:
Sec. 870.5310 Automated external defibrillator system.
(a) Identification. An automated external defibrillator (AED)
system consists of an AED and those accessories necessary for the AED
to detect and interpret an electrocardiogram and deliver an electrical
shock (e.g., battery, pad electrode, adapter, and hardware key for
pediatric use). An AED system analyzes the patient's electrocardiogram,
interprets the cardiac rhythm, and automatically delivers an electrical
shock (fully automated AED), or advises the user to deliver the shock
(semi-automated or shock advisory AED) to treat ventricular
fibrillation or pulseless ventricular tachycardia.
* * * * *
(c) Date PMA or notice of completion of PDP is required. A PMA will
be required to be submitted to the Food and Drug Administration by
April 29, 2015, for any AED that was in commercial distribution before
May 28, 1976, or that has, by April 29, 2015, been found to be
substantially equivalent to any AED that was in commercial distribution
before May 28, 1976. A PMA will be required to be submitted to the Food
and Drug Administration by April 29, 2015, for any AED accessory
described in paragraph (a) that was in commercial distribution before
May 28, 1976, or that has, by April 29, 2015, been found to be
substantially equivalent to any AED accessory described in paragraph
(a) that was in commercial distribution before May 28, 1976. Any other
AED and AED accessory described in paragraph (a), shall have an
approved PMA or declared completed PDP in effect before being placed in
commercial distribution.
Dated: January 23, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-01619 Filed 1-28-15; 8:45 am]
BILLING CODE 4164-01-P