[Federal Register Volume 78, Number 98 (Tuesday, May 21, 2013)]
[Proposed Rules]
[Pages 29672-29680]
[FR Doc No: 2013-12122]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 870

[Docket No. FDA-2013-N-0487]

Cardiovascular Devices; Reclassification of External Counter-
Pulsating Devices for Treatment of Chronic Stable Angina; Effective
Date of Requirement for Premarket Approval for External Counter-
Pulsating Devices for Other Specified 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 external counter-pulsating (ECP)
devices for treatment of chronic stable angina that is refractory to
optimal anti-anginal medical therapy and without options for
revascularization, which is 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 ECP devices for other intended uses specified in this proposed
order. 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 for
other intended uses specified in this proposed order. 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 on this proposed
order by August 19, 2013. FDA intends that, if a final order based on
this proposed order is issued, anyone who wishes to continue to market
ECP devices for specified intended uses listed in section IX 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 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-0487, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Mail/Hand delivery/Courier (for paper or CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name
and Docket No. FDA-2013-N-0487 for this rulemaking. All comments
received may be posted without change to http://www.regulations.gov,
including any personal information provided. For additional information
on submitting comments, see the ``Comments'' heading of the
SUPPLEMENTARY INFORMATION section.
    Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Angela Krueger, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1666, Silver Spring, MD 20993,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
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
(Public Law 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), establishes a comprehensive
system for the regulation of medical devices intended for human use.
Section 513 of the FD&C Act (21 U.S.C. 360c) established three
categories (classes) of devices, reflecting the regulatory controls
needed to provide reasonable assurance of their safety and
effectiveness. The three categories of devices are class I (general
controls), class II (special controls), and class III (premarket
approval).
    Under section 513 of the FD&C Act, devices that were in commercial
distribution before the enactment of the 1976 amendments, May 28, 1976
(generally referred to as preamendments devices), are classified after
FDA has: (1) Received a recommendation from a device classification
panel (an FDA advisory committee); (2) published the panel's
recommendation for comment, along with a proposed regulation
classifying the device; and (3) published a final regulation
classifying the device. FDA has classified most preamendments devices
under these procedures.
    Devices that were not in commercial distribution prior to May 28,
1976 (generally referred to as postamendments devices), are
automatically classified by section 513(f) of the FD&C Act into class
III without any FDA rulemaking process. Those devices remain in class
III and require premarket approval unless, and until, the device is
reclassified into class I or II or FDA issues an order finding the
device to be substantially equivalent, in accordance with section
513(i) of the FD&C Act, to a predicate device that does not require
premarket approval. The Agency determines whether new devices are
substantially equivalent to predicate devices by means of premarket
notification procedures in section 510(k) of the FD&C Act (21 U.S.C.
360(k)) and part 807 (21 CFR part 807).
    A preamendments device that has been classified into class III and
devices found substantially equivalent by means of premarket
notification (510(k)) procedures to such a preamendments device or to a
device within that type may be marketed without submission of a PMA
until FDA issues a final order under section 515(b) of the FD&C Act (21
U.S.C. 360e(b)) requiring premarket approval or until the device is
subsequently reclassified into class I or class II.
    Although, under the FD&C Act, the manufacturer of class III
preamendments device may respond to the call for PMAs by filing a PMA
or a notice of completion of a PDP, in practice, the option of filing a
notice of completion of a PDP has not been used. For simplicity,
although corresponding requirements for PDPs remain available to
manufacturers in response to a final order under section 515(b) of the
FD&C Act, this document will refer only to the requirement for the
filing and receiving approval of a PMA.
    On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA (126
Stat. 1056) 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 (126 Stat. 1056) 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
ECP devices for treatment of chronic stable angina that is refractory
to optimal anti-anginal medical therapy and without options for
revascularization 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) must be
``valid scientific evidence,'' as defined in section 513(a)(3) of the
FD&C Act and Sec.  860.7(c)(2) (21 CFR 860.7(c)(2)). (See, e.g.,
General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens
Association v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S.
1062 (1985).)
    FDA relies upon ``valid scientific evidence'' in the classification
process to determine the level of regulation for devices. To be
considered in the reclassification process, the ``valid scientific
evidence'' upon which the Agency relies must be publicly available.
Publicly available information excludes trade secret and/or
confidential commercial information, e.g., the contents of a pending
PMA. (See section 520(c) of the FD&C Act (21 U.S.C. 360j(c)).) Section
520(h)(4) of the FD&C Act, added by FDAMA, provides that FDA may use,
for reclassification of a device, certain information in a PMA 6 years
after the application has been approved. This can include information
from clinical and preclinical tests or studies that demonstrate the
safety or effectiveness of the device but does not include descriptions
of methods of manufacture or product composition and other trade
secrets.
    Section 513(e)(1) of the FD&C Act sets forth the process for
issuing a final order. Specifically, prior to the issuance of a final
order reclassifying a device, the following must occur: (1) Publication
of a proposed order in the Federal Register; (2) a meeting of a device
classification panel described in section 513(b) of the FD&C Act; and
(3) consideration of comments to a public docket. FDA has held a
meeting of a device classification panel described in section 513(b) of
the FD&C Act with respect to external-counter pulsating 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. Section 510(m) of the
FD&C Act 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 ECP devices for Certain
Specified Intended Uses.\1\
---------------------------------------------------------------------------

    \1\ For the purposes of this proposed order, the term ``Certain
Specified Intended Uses'' includes the following intended uses:
     Unstable angina pectoris;
     Acute myocardial infarction;
     Cardiogenic shock;
     Congestive heart failure;
     Postoperative treatment of patients who have undergone
coronary artery bypass surgery;
     Peripheral arterial disease associated with the
following: Ischemic ulcers rest pain or claudication; threatened
gangrene; insufficient blood supply at an amputation site;
persisting ischemia after embolectomy or bypass surgery; and/or pre-
and post-arterial reconstruction to improve runoff;
     Diabetes complicated by peripheral arterial disease or
other conditions possibly related to arterial insufficiency
including the following: Nocturnal leg cramps and/or necrobiosis
diabeticorum;
     Venous diseases, including the following: Prophylaxis
of deep vein thrombophlebitis; edema (e.g., chronic lymphedema) and/
or induration (e.g., stasis dermatitis) associated with chronic
venous stasis; venous stasis ulcers; and/or thrombophlebitis;
     Athletic injuries, including the following: Charley
horses, pulled muscles, and/or edematous muscles; and
     Necrotizing cellulitis.
---------------------------------------------------------------------------

    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, payors,
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 external-
counter pulsating 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)
proposed findings with respect to the degree of risk of illness or
injury designed to be eliminated or reduced by requiring the device to
have an approved PMA or a declared completed PDP and the benefit to the
public from the use of the device, (3) an opportunity for the
submission of comments on the proposed order and the proposed findings,
and (4) an opportunity to request a change in the classification of the
device based on new information relevant to the classification of the
device.
    Section 515(b)(3) of the FD&C Act provides that FDA shall, after
the close of the comment period on the proposed order, consideration of
any comments received, and a meeting of a device classification panel
described in section 513(b) of the FD&C Act, issue a final order to
require premarket approval or publish a document terminating the
proceeding together with the reasons for such termination. If FDA
terminates the proceeding, FDA is required to initiate reclassification
of the device under section 513(e) of the FD&C Act, unless the reason
for termination is that the device is a banned device under section 516
of the FD&C Act (21 U.S.C. 360f)
    A preamendments class III device may be commercially distributed
without a PMA until 90 days after FDA issues a final order (a final
rule issued under section 515(b) of the FD&C Act prior to the enactment
of FDASIA is considered to be a final order for purposes of section
501(f) of the FD&C Act (21 U.S.C. 351(f))) requiring premarket approval
for the device, or 30 months after final classification of the device
under section 513 of the FD&C Act, whichever is later. For ECP 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 7966; February 5, 1980). Therefore, if the proposal to
require premarket approval for ECP devices for Certain Specified
Intended Uses 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 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)(2) of the FD&C Act, interested
persons are being offered the opportunity to request reclassification
of ECP devices for Certain Specified Intended Uses.

II. Regulatory History of the Device

    In the preamble to the proposed rule (44 FR 13426, March 9, 1979),
the Cardiovascular Device Classification Panel (the 1979 Panel)
recommended that ECP devices be classified into class III because the
device is life-supporting and is potentially hazardous to life or
health even when properly used. The 1979 Panel noted that the device
surrounds the limbs to which it is attached, is in direct contact with
the skin, and is used in a clinical environment where excessive leakage
current can be a serious hazard. As a result the electrical
characteristics of this device need to meet certain requirements. The
1979 Panel further noted that the performance characteristics,
including accuracy, reproducibility, and any limitations on the
device's cardiac synchronization and pressure application should be
maintained at a generally accepted satisfactory level and should be
made known to the user through special labeling. In addition, the
device is used with other devices in a system that may be hazardous if
not satisfactorily assembled, used, and maintained. The 1979 Panel
indicated that general controls alone would not provide sufficient
control over the performance characteristics of the device, and that
there was not sufficient information to establish a performance
standard to provide assurance of the safety and effectiveness of the
device. Consequently, the 1979 Panel believed that premarket approval
was necessary to assure the safety and effectiveness of the device. In
1980, FDA classified external counter-pulsating devices into class III
after receiving no comments on the proposed rule (45 FR 7966, February
5, 1980).
    In 1987, FDA published a clarification by codifying a statement
that no effective date had been established for the requirement for
premarket approval for external counter-pulsating devices (52 FR 17732
at 17737, May 11, 1987).
    In 2009, FDA published an order for the submission of information
on external counter-pulsating devices by August 7, 2009 (74 FR 16214,
April 9, 2009). FDA received five responses to that order from device
manufacturers recommending that ECP devices be reclassified to class
II. The manufacturers stated that safety and effectiveness of these
devices may be assured by device design, performance testing, and
labeling (special controls).
    As explained further in sections VII and XI, a meeting of the
Circulatory System Devices Panel (the 2012 Panel) took place December
5, 2012, to discuss whether ECP devices should be reclassified or
remain in class III. The 2012 Panel recommended that ECP devices
intended for treatment of chronic stable angina that is refractory to
optimal anti-anginal medical therapy and without options for
revascularization be reclassified to class II with special controls and
ECP devices for Certain Specified Intended Uses remain in class III.
Because the safety and effectiveness of ECP devices for Certain
Specified Intended Uses has not been established through adequate
scientific evidence, the device presents a potential unreasonable risk
of injury given that the benefit of ECP devices for these uses is
unknown. In addition, there was insufficient information to establish
special controls for these uses. FDA is not aware of new information
that would provide a basis for a different recommendation or findings.

III. Device Description

    An external counter-pulsating device is a noninvasive device used
to assist the heart by applying positive or negative pressure to one or
more of the body's limbs in synchrony with the heart cycle. An ECP
system typically consists of a treatment table, a set of pressure
cuffs, and a control console. The control console controls a pneumatic
circuit that inflates and deflates the pressure cuffs. The inflatable
pressure cuffs are wrapped around the calves, the lower and upper
thighs, and/or the buttocks. They are rapidly and sequentially
inflated, starting from the calves and moving proximally during the
diastolic phase of a cardiac cycle. This creates an arterial retrograde
flow of blood towards the heart and increases blood flow to the
coronary arteries at a time when resistance to the coronary blood flow
is low. The inflation of the cuffs also simultaneously increases the
volume of venous blood returned to the right side of the heart,
providing greater filling of the ventricle for ejection. The
synchronization between the cardiac cycle and the inflation/deflation
cycle of the cuffs is coordinated by custom software contained within
the control console that monitors and interprets the patient's
electrocardiogram and heart rhythm.

IV. Proposed Reclassification

    FDA is proposing that ECP devices for treatment of chronic stable
angina that is refractory to optimal anti-anginal medical therapy and
without options for revascularization 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 Act and Sec.  860.130, based on new information with respect to
the devices and taking into account the public health benefit of the
use of the device and the nature and known incidence of the risk of the
device, FDA, on its own initiative, is proposing to reclassify this
preamendments class III device into class II for the treatment of
chronic stable angina that is refractory to optimal anti-anginal
medical therapy and without options for revascularization. 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 ECP devices for treatment of chronic
stable angina that

is refractory to optimal anti-anginal medical therapy and without
options for revascularization.
    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 ECP devices for treatment of chronic stable angina that
is refractory to optimal anti-anginal medical therapy and without
options for revascularization in accordance with the reserved criteria
set forth in section 513(a) of the FD&C Act and decided that the device
does require premarket notification. Therefore, the Agency does not
intend to exempt this proposed class II device from premarket
notification (510(k)) submission.

V. Risks to Health

    After considering available information, including the
recommendations of the advisory committees (panels) for the
classification of these devices, FDA has evaluated the risks to health
associated with the use of ECP devices and determined that the
following risks to health are associated with its use:
     Cardiac arrhythmias--Excessive electrical leakage current
may disturb the normal electrophysiology of the heart, leading to the
onset of cardiac arrhythmias.
     Trauma/Irritation to the limb--Improper mechanical design,
including selection of materials, may cause bruising, blistering,
muscle aches, and/or pain to the limb(s).
     Ineffective cardiac assistance--Improper timing or failure
to synchronize the device with the appropriate phase of the cardiac
cycle may lead to ineffective cardiac assistance by the device.

VI. Summary of Reasons for Reclassification

    If properly manufactured and used, ECP devices can provide a
treatment option for patients with chronic stable angina that is
refractory to optimal anti-anginal medical therapy and without options
for revascularization, especially patients who are not candidates for
treatment by revascularization and who are refractory to medical
therapy, by increasing blood flow to the coronary arteries and
increasing the volume of venous blood returned to the right side of the
heart, providing greater filling of the ventricle for ejection. FDA
believes that ECP devices intended for treatment of chronic stable
angina that is refractory to optimal anti-anginal medical therapy and
without options for revascularization should be reclassified from class
III to class II because 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. In addition, there is now adequate
effectiveness information sufficient to establish special controls to
provide such assurance.

VII. Summary of Data Upon Which the Reclassification Is Based

    Since the time of the 1979 Panel recommendation, sufficient
evidence has been developed to support a reclassification of ECP
devices to class II with special controls for the treatment of chronic
stable angina that is refractory to optimal anti-anginal medical
therapy and without options for revascularization. FDA has been
reviewing these devices for many years and their risks are well known.
FDA conducted a comprehensive review of available literature for ECP
devices for treatment of chronic stable angina. FDA's review found 4
randomized controlled trials (Refs. 1 to 4), 21 observational studies,
and a meta-analysis of 13 individual studies that provided consistent
evidence of the effectiveness of ECP devices for the treatment of
chronic stable angina that is refractory to optimal anti-anginal
medical therapy and without options for revascularization. Although all
of the studies of ECP for the treatment of angina considered
individually have various limitations, the consistency of the study
results, the wide range of angina-related endpoints involved in the
studies, the large magnitude of the demonstrated beneficial outcomes,
the long duration (up to 3 years) of some of the beneficial outcomes,
and the fact that many or most of the subjects had a disease that was
refractory to the effects of any other treatment, all support a
conclusion of reasonable evidence for the effectiveness of ECP in the
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization. The
safety profile of ECP devices has been established based on the few
relevant adverse events reported in the literature or through FDA's
Manufacturer and User Facility Device Experience (MAUDE) database. In
addition, bench studies designed to demonstrate the devices' ability to
function as intended have been well characterized.
    The 2012 Panel discussed and made recommendations regarding the
regulatory classification of ECP 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.
    FDA's presentation to the 2012 Panel included a summary of the
available safety and effectiveness information for ECP devices for
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization,
including adverse event reports from the MAUDE database and available
literature. Based on the available scientific literature that supports
that ECP may be beneficial for patients with chronic stable angina who
are not revascularization candidates and who are refractory to optimal
medical therapy, FDA recommended to the 2012 Panel that ECP devices for
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization be
reclassified to class II (special controls). The 2012 Panel agreed with
FDA's conclusion that the available scientific evidence is adequate to
support the safety and effectiveness of ECP devices for treatment of
chronic stable angina that is refractory to optimal anti-anginal
medical therapy and without options for revascularization.
    The 2012 Panel also agreed with the identified risks to health
outlined in section V. FDA recommended that a fourth risk to health,
failure to identify the correct patient population, be considered in
the 2012 Panel's deliberations. FDA proposed this risk to health to
capture situations in which the device was used properly but patients
experienced adverse events associated with their underlying
comorbidities. For example, based on FDA's evaluation of Medical Device
Reporting Regulations more than half were associated with patients with
congestive heart failure who experience exacerbation of the condition
following use of the device. However, the 2012 Panel questioned whether
failure to identify the correct patient population was really a risk to
health and noted that the risk is vague and too broad. FDA agreed with
the 2012 Panel's recommendation and removed the proposed fourth risk.
The 2012 Panel agreed with FDA's proposed special controls outlined in
section VIII. In addition, the 2012 Panel also agreed with FDA that ECP
devices are not considered to be life-supporting. This differs from the
1979 Panel's recommendation outlined in the proposed rule for this
device type (44 FR 13426, March 9, 1979). The 2012 Panel transcript and
other meeting

materials are available on FDA's Web site (Ref. 5).

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) Nonclinical performance evaluation of the device must
demonstrate a reasonable assurance of safety and effectiveness for
applied pressure, synchronization of therapy with the appropriate phase
of the cardiac cycle, and functionality of alarms during a device
malfunction or an abnormal patient condition;
    (2) Reliabilities of the mechanical and electrical systems must be
established through bench testing under simulated use conditions and
matched by appropriate maintenance schedules;
    (3) Software design and verification and validation must be
appropriately documented;
    (4) The skin-contacting components of the device must be
demonstrated to be biocompatible;
    (5) Appropriate analysis and testing must be conducted to verify
electrical safety and electromagnetic compatibility of the device; and
    (6) Labeling must bear all information required for the safe and
effective use of the device, including a detailed summary of the
device-related and procedure-related complications pertinent to use of
the device.
    ECP 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 Sec.  870.5225(a) (21 CFR 870.5225(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 control
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
Sec.  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 within 90 days after
issuance of any final order based on this proposal for ECP devices
intended for the following uses (Certain Specified Intended Uses):
     Unstable angina pectoris;
     Acute myocardial infarction;
     Cardiogenic shock;
     Congestive heart failure;
     Postoperative treatment of patients who have undergone
coronary artery bypass surgery;
     Peripheral arterial disease associated with the following:
Ischemic ulcers rest pain or claudication, threatened gangrene,
insufficient blood supply at an amputation site, persisting ischemia
after embolectomy or bypass surgery, and/or pre and post-arterial
reconstruction to improve runoff;
     Diabetes complicated by peripheral arterial disease or
other conditions possibly related to arterial insufficiency including
the following: Nocturnal leg cramps and/or necrobiosis diabeticorum;
     Venous diseases, including the following: Prophylaxis of
deep vein thrombophlebitis, edema (e.g., chronic lymphedema) and/or
induration (e.g., stasis dermatitis) associated with chronic venous
stasis, venous stasis ulcers, and/or thrombophlebitis;
     Athletic injuries, including the following: Charley
horses, pulled muscles, and/or edematous muscles; and
     Necrotizing cellulitis.
    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 any one or more Certain Specified Intended Uses, 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. 21 CFR 806.10(a)(2) requires a device manufacturer or
importer initiating a correction to remedy a violation of the FD&C Act
that may present a risk to health to submit a written report of the
correction to FDA.
    FDA intends that under Sec.  812.2(d), the preamble to any final
order based on this proposal will state that, as of the date on which
the filing of a PMA is required to be filed, the exemptions from the
requirements of the IDE regulations for preamendments class III devices
in Sec.  812.2(c)(1) and (c)(2) will cease to apply to any device that
is: (1) Not legally on the market on or before that date or (2) legally
on the market on or before that date but for which a PMA is not filed
by that date, or for which PMA approval has been denied or withdrawn.
    If a PMA for a class III device is not filed with FDA within 90
days after the date of issuance of any final order requiring premarket
approval for the device, the device would be deemed adulterated under
section 501(f) of the FD&C Act. The device may be distributed for
investigational use only if the requirements of the IDE regulations are
met. The requirements for significant risk devices include submitting
an IDE application to FDA for review and approval. An approved IDE is
required to be in effect before an investigation of the device may be
initiated or continued under Sec.  812.30. FDA, therefore, recommends
that IDE applications be submitted to FDA at least 30 days before the
end of the 90-day period after the issuance of the final order to avoid
interrupting any ongoing investigations.
    Because ECP devices intended for the treatment of chronic stable
angina that is refractory to optimal anti-Anginal medical therapy and
without options for revascularization 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 ECP devices
intended for the treatment of chronic stable angina that is refractory
to optimal anti-anginal medical therapy and without options for
revascularization.

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 for Certain Specified Intended Uses and (2)
the benefits to the public from the use of ECP devices for Certain
Specified Intended Uses.
    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 can be found in 44 FR 13426, 45 FR 7966, and 52 FR 17732 at
17737.

XI. Device Subject to the Proposal to Require a PMA--External Counter-
Pulsating Devices for Uses Other Than Treatment of Chronic Stable
Angina That Is Refractory to Optimal Anti-Anginal Medical Therapy and
Without Options for Revascularization (Sec.  870.5225(c))

A. Identification

    An external counter-pulsating device is a noninvasive, prescription
device used to assist the heart by applying positive or negative
pressure to one or more of the body's limbs in synchrony with the heart
cycle.

B. Summary of Data

    For uses other than treatment of chronic stable angina that is
refractory to optimal anti-anginal medical therapy and without options
for revascularization as specified in section IX, 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 ECP devices for uses other than
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization.
Review of the published scientific literature revealed a lack of valid
scientific evidence to support indications other than treatment of
chronic stable angina that is refractory to optimal anti-anginal
medical therapy and without options for revascularization. There were
few studies that discussed other uses and those studies did not provide
evidence of reasonable assurance of effectiveness due to lack of
relevant details regarding study design, conduct and results, use of
flawed study designs, and publication bias (Refs. 6 to 11). FDA
presented the findings of our literature search for ECP devices for
uses other than treatment of chronic stable angina that is refractory
to optimal anti-anginal medical therapy and without options for
revascularization to the Circulatory System Devices Panel (the Panel)
on December 5, 2012. Based on FDA's findings, the Panel concluded that
available scientific evidence is not adequate to support the
effectiveness of ECP devices for uses other than treatment of chronic
stable angina that is refractory to optimal anti-anginal medical
therapy and without options for revascularization. The Panel also
recommended that ECP devices for Certain Specified Intended Uses should
remain in class III (subject to premarket approval application).
Although the Panel noted that ECP devices are not life-supporting, the
devices present a potential unreasonable risk of injury given that
risks to health exist that are not balanced by a benefit that has been
established through adequate scientific evidence to demonstrate safety
and effectiveness.
    The Panel transcript and other meeting materials are available on
FDA's Web site (Ref. 5).

C. Risks to Health

    The risks to health for ECP devices for uses other than treatment
of chronic stable angina that is refractory to optimal anti-anginal
medical therapy and without options for revascularization are the same
as outlined in section V.

D. Benefits of ECP Devices

    As discussed previously, there is limited scientific evidence
regarding the effectiveness of ECP devices for uses other than
treatment of chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization.
Because the benefits of these devices for such uses are unknown, it is
impossible to estimate the direct effect of the devices on patient
outcomes. However, claims for the devices state that the devices have
the potential to benefit the public by augmenting cardiac output,
increasing coronary blood flow, and stimulating circulation in the
lower extremities.

XII. PMA Requirements

    A PMA for ECP devices for Certain Specified Intended Uses 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 document; (2) the effectiveness of the device that
is the subject of the application; and (3) full reports of all
preclinical and clinical information from investigations on the safety
and effectiveness of the device for which premarket approval is sought.
    A PMA must include valid scientific evidence to demonstrate
reasonable assurance of the safety and effectiveness of the device for
its intended use (see Sec.  860.7(c)(1)). Valid scientific evidence is
``evidence from well-controlled investigations, partially controlled
studies, studies and objective trials without matched controls, well-
documented case histories conducted by qualified experts, and reports
of significant human experience with a marketed device, from which it
can fairly and responsibly be concluded by qualified experts that there
is reasonable assurance of the safety and effectiveness of a device
under its conditions of use * * * Isolated case reports, random
experience, reports lacking sufficient details to permit scientific
evaluation, and unsubstantiated opinions are not regarded as valid
scientific evidence to show safety or effectiveness.'' (See Sec.
860.7(c)(2).)

XIII. Opportunity To Request a Change in Classification

    Before requiring the filing of a PMA for a device, FDA is required
by section 515(b)(2)(D) of the FD&C Act to provide an opportunity for
interested persons to request a change in the classification of the
device based on new information relevant to the classification. Any
proceeding to reclassify the device will be under the authority of
section 513(e) of the FD&C Act.
    A request for a change in the classification of ECP devices for
Certain Specified Intended Uses is to be in the form of a
reclassification petition containing the information required by Sec.
860.123, including new information relevant to the classification of
the device.

XIV. Codification of Orders

    Prior to the amendments by FDASIA, section 513(e) of the FD&C Act
provided for FDA to issue regulations to reclassify devices and section
515(b) of the FD&C Act provided for FDA to issue regulations to require
approval of an application for premarket approval for preamendments
devices or devices found to be substantially equivalent to
preamendments devices. Because sections 513(e) and 515(b) as amended
require FDA to issue final orders rather than regulations, FDA will
continue to codify reclassifications and requirements for approval of
an application for premarket approval, resulting from changes issued in
final orders, in the Code of Federal Regulations. Therefore, under
section 513(e)(1)(A)(i) of the FD&C Act, as amended by FDASIA, in this
proposed order, we are proposing to revoke the requirements in Sec.
870.5225 related to the classification of external counter-pulsating
devices for chronic stable angina that is refractory to optimal anti-
anginal medical therapy and without options for revascularization as
class III

devices and to codify the reclassification of external counter-
pulsating devices for chronic stable angina that is refractory to
optimal anti-anginal medical therapy and without options for
revascularization 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, 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 part 812 have been approved under
OMB control number 0910-0078.

XVII. Proposed Effective Date

    FDA is proposing that any final order based on this proposed order
become effective 90 days after date of publication of the final order
in the Federal Register.

XVIII. Comments

    Interested persons may submit either electronic comments regarding
this document to http://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES). It is only necessary to
submit one set of comments. Identify comments with the docket number
found in the brackets in the heading of this document. Received
comments may be seen in the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday, and will be posted to the
docket at http://www.regulations.gov.

XIX. References

    The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday,
and are available electronically at http://www.regulations.gov. (FDA
has verified the Web site address in this reference section, but FDA is
not responsible for any subsequent changes to the Web site after this
document publishes in the Federal Register.)

1. Arora, R. R., T. M. Chou, D. Jain, et al., ``The Multicenter
Study of Enhanced External Counterpulsation (MUST-EECP): Effect of
EECP on Exercise-Induced Myocardial Ischemia and Anginal Episodes,''
Journal of the American College of Cardiology, vol. 33, pp. 1833-
1840, 1999.
2. Arora, R. R., T. M. Chou, D. Jain, et al., ``Effects of Enhanced
External Counterpulsation on Health-Related Quality of Life Continue
12 Months After Treatment: A Substudy of the Multicenter Study of
Enhanced External Counterpulsation,'' Journal of Investigative
Medicine, vol. 50, pp. 25-32, 2002.
3. Gloekler, S., P. Meier, S. F. de Marchi, et al., ``Coronary
Collateral Growth by External Counterpulsation: A Randomised
Controlled Trial,'' Heart, vol. 96, pp. 202-207, 2010.
4. Casey, D. P., D. T. Beck, W. W. Nichols, et al., ``Effects of
Enhanced External Counterpulsation on Arterial Stiffness and
Myocardial Oxygen Demand in Patients With Chronic Angina Pectoris,''
American Journal of Cardiology, vol. 107, pp. 1466-1472, 2011.
5. FDA, the Panel transcript and other meeting materials, (http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm300073.htm).
6. Abbottsmith, C. W., E. S. Chung, T. Varricchione, et al.,
``Enhanced External Counterpulsation Improves Exercise Duration and
Peak Oxygen Consumption in Older Patients With Heart Failure: A
Subgroup Analysis of the PEECH Trial,'' Congestive Heart Failure,
vol. 12, pp. 307-311, 2006.
7. Feldman, A. M., M. A. Silver, G. S. Francis, et al., ``Enhanced
External Counterpulsation Improves Exercise Tolerance in Patients
With Chronic Heart Failure,'' Journal of the American College of
Cardiology, vol. 48, pp. 1198-1205, 2006.
8. Kozdag, G., G. Ertas, F. Aygun, et al., ``Clinical Effects of
Enhanced External Counterpulsation Treatment in Patients With
Ischemic Heart Failure,'' Anadolu Kardiyol Derg, vol. 12, pp. 214-
221, 2012.
9. Triulzi, E., S. Devizzi, G. Rovelli, et al., [``Efficacy of
Enhanced Aortic Diastolic Pressure With An External Counterpulsation
Method in the Acute Myocardial Infarction'' (author's translation)],
Giornale Italiano di Cardiologia, vol. 10, pp. 690-702, 1980.
10. Vijayaraghavan, K., L. Santora, J. Kahn, et al., ``New Graduated
Pressure Regimen for External Counterpulsation Reduces Mortality and
Improves Outcomes in Congestive Heart Failure: A Report From the
Cardiomedics External Counterpulsation Patient Registry,''
Congestive Heart Failure, vol. 11, pp. 147-152, 2005.
11. Amsterdam, E. Z., J. Banas, J. M. Criley, et al., ``Clinical
Assessment of External Pressure Circulatory Assistance in Acute
Myocardial Infarction,'' American Journal of Cardiology, vol. 45,
pp. 349-356, 1980.

List of Subjects in 21 CFR Part 870

    Medical devices, Cardiovascular devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 870 be amended as follows:

PART 870--CARDIOVASCULAR DEVICES

0
1. The authority citation for 21 CFR part 870 continues to read as
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Revise Sec.   870.5225 to read as follows:

Sec.  870.5225  External counter-pulsating device.

    (a) Identification. An external counter-pulsating device is a
noninvasive, prescription device used to assist the heart by applying
positive or negative pressure to one or more of the body's limbs in
synchrony with the heart cycle.
    (b) Classification. (1) Class II (special controls) when the device
is intended for the treatment of chronic stable angina that is
refractory to optimal anti-anginal medical therapy and without options
for revascularization. The special controls for this device are:
    (i) Nonclinical performance evaluation of the device must
demonstrate a reasonable assurance of safety and effectiveness for
applied pressure, synchronization of therapy with the appropriate phase
of the cardiac cycle, and functionality of

alarms during a device malfunction or an abnormal patient condition;
    (ii) Reliabilities of the mechanical and electrical systems must be
established through bench testing under simulated use conditions and
matched by appropriate maintenance schedules;
    (iii) Software design and verification and validation must be
appropriately documented;
    (iv) The skin-contacting components of the device must be
demonstrated to be biocompatible;
    (v) Appropriate analysis and testing must be conducted to verify
electrical safety and electromagnetic compatibility of the device; and
    (vi) Labeling must bear all information required for the safe and
effective use of the device, including a detailed summary of the
device-related and procedure-related complications pertinent to use of
the device.
    (2) Class III (premarket approval) for the following intended uses:
Unstable angina pectoris; acute myocardial infarction; cardiogenic
shock; congestive heart failure; postoperative treatment of patients
who have undergone coronary artery bypass surgery; peripheral arterial
disease associated with ischemic ulcers rest pain or claudication,
threatened gangrene, insufficient blood supply at an amputation site,
persisting ischemia after embolectomy or bypass surgery, and/or pre-
and post-arterial reconstruction to improve runoff; diabetes
complicated by peripheral arterial disease or other conditions possibly
related to arterial insufficiency including nocturnal leg cramps and/or
necrobiosis diabeticorum; venous diseases, including prophylaxis of
deep vein thrombophlebitis, edema (e.g., chronic lymphedema) and/or
induration (e.g., stasis dermatitis) associated with chronic venous
stasis, venous stasis ulcers, and/or thrombophlebitis; athletic
injuries, including Charley horses, pulled muscles and/or edematous
muscles; necrotizing cellulitis.
    (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 THAT WILL BE 90 DAYS AFTER DATE OF
PUBLICATION OF A FUTURE FINAL ORDER IN THE FEDERAL REGISTER], for any
external counter-pulsating device, with an intended use described in
(b)(2) of this section, that was in commercial distribution before May
28, 1976, or that has, on or before [A DATE WILL BE ADDED THAT WILL BE
90 DAYS AFTER DATE OF PUBLICATION OF A FUTURE FINAL ORDER IN THE
FEDERAL REGISTER], been found to be substantially equivalent to any
external counter-pulsating device, with an intended use described in
(b)(2) of this section, that was in commercial distribution before May
28, 1976. Any other external counter-pulsating device with an intended
use described in (b)(2) of this section shall have an approved PMA or
declared completed PDP in effect before being placed in commercial
distribution.

    Dated: May 15, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-12122 Filed 5-20-13; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register Volume 88, Number 145 (Monday, July 31, 2023)]
[Notices]
[Pages 49467-49469]
[FR Doc No: 2023-16150]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-N-2459]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Product Jurisdiction and Combination Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
announcing an opportunity for public comment on the proposed collection
of certain information by the Agency. Under the Paperwork Reduction Act
of 1995 (PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on information collection
associated with product jurisdiction and combination product
regulations.

DATES: Either electronic or written comments on the collection of
information must be submitted by September 29, 2023.

ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of September 29, 2023. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments.

Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because
your comment will be made public, you are solely responsible for
ensuring that your comment does not include any confidential
information that you or a third party may not wish to be posted, such
as medical information, your or anyone else's Social Security number,
or confidential business information, such as a manufacturing process.
Please note that if you include your name, contact information, or
other information that identifies you in the body of your comments,
that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2023-N-2459 for ``Product Jurisdiction and Combination Products.''
Received comments, those filed in a timely manner (see ADDRESSES), will
be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday,<PHONE_NUMBER>.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852,<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed extension of
the existing collection of information set forth in this document.
    With respect to the following collection of information, FDA
invites comments on these topics: (1) whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.

Product Jurisdiction and Combination Products--21 CFR Parts 3 and 4

OMB Control Number 0910-0523--Extension

    This information collection helps support implementation of
statutory requirements that govern product jurisdiction and combination
products. Congress expressly directed FDA to assign combination
products to the appropriate Agency component for regulation as set
forth in section 503(g) of the Federal Food, Drug, and Cosmetic Act
(FD&C Act) (21 U.S.C. 353(g)). Congress also expressly directed FDA to
determine the classification of a product as a drug, biological
product, device, or combination product, or the component of the Agency
that will regulate the product, as applicable, in response to a request
submitted under section 563 of the FD&C Act (21 U.S.C. 360bbb-2).
    Regulations in 21 CFR part 3 provide for product classification
determinations and FDA designation on which Agency component will have
primary jurisdiction for any drug, device, biological, or combination
product, where such jurisdiction is unclear or in dispute. These
determinations are made by our Office of Combination Products (OCP)
upon receiving Requests for Designation (RFDs). We maintain a web page
that includes contact and resource information pertaining to the RFDs
process at https://www.fda.gov/combination-products/jurisdictional-information. As communicated on our web page, FDA welcomes comments
from interested stakeholders on issues pertaining to OCP and encourages
medical product developers to contact us if they are uncertain about
the classification or assignment of their products and with questions
regarding premarket or postmarket considerations for combination
products. A dedicated mailbox is established at [email protected].

    Similar to the RFD process, we have established the Pre-RFD process
for sponsors to obtain preliminary, nonbinding feedback regarding
medical product classification and assignment. Although Forms FDA 5003,
5004, and 5005 (pre-request and request for designation forms) were
previously developed to facilitate information collection for Pre-RFDs
and RFDs, we have more recently issued the following Agency guidance
documents to provide instruction and recommendations to respondents
regarding the submission of RFDs and Pre-RFDs.
     The guidance document entitled, ``How to Write a Request
for Designation'' (April 2011), provides instruction regarding the
information that needs to be submitted to OCP in an RFD as described in
21 CFR 3.7. The guidance is available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-write-request-designation-rfd.
     The guidance document entitled ``How to Prepare a Pre-
Request for Designation,'' (February 2018) was developed to assist
sponsors in obtaining a preliminary, non-binding assessment regarding
the classification and assignment of products from OCP through the Pre-
RFD process. The guidance explains the Pre-RFD process and helps a
sponsor understand the type of information to provide in a Pre-RFD
submission. The guidance is available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-prepare-pre-request-designation-pre-rfd.
     This information collection also includes burden
associated with Combination Product Agreement Meetings (CPAM) requests.
The guidance document entitled, ``Requesting FDA Feedback on
Combination Products,'' (December 2020) was developed to discuss ways
in which combination product sponsors can obtain feedback from FDA on
scientific and regulatory questions and to describe best practices for
FDA and sponsors when interacting on these topics. The guidance is
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requesting-fda-feedback-combination-products.
    The guidance documents were issued consistent with our good
guidance practice regulations in 21 CFR 10.115, which provide for
public comment at any time.
    The information collection also includes regulations in 21 CFR part
4 that govern current good manufacturing practice requirements and
postmarketing safety requirements for combination products. We expect,
however, that burden attendant to the associated recordkeeping,
reporting, and/or disclosure activities is already accounted for in
approved information collections that apply to drug, device, and/or
biologic products specifically and respectively. Therefore, we do not
ascribe separate burden in this information collection request for the
activities generated by these requirements.
    Respondents to the information collection are sponsors of medical
products, including combination products. Based on submissions received
by OCP during fiscal years 2020, 2021, and 2022, we account for 135
respondents annually.
    We estimate the burden of this collection of information as
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
    21 CFR section; activity         Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
3.7; request for designation                  55               1              55              24           1,320
 (RFD)..........................
Pre-RFD submissions.............              77               1              77              24           1,848
CPAM requests...................               3               1               3              25              75
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............           3,243
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Our estimated burden reflects a decrease in the number of
respondents (four respondents) and a corresponding decrease in total
hours (96 hours). Based on a recent evaluation of CPAM requests
received from each product center in fiscal years 2020, 2021, and 2022,
our estimated annual burden for CPAM requests remains unchanged.

    Dated: July 26, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-16150 Filed 7-28-23; 8:45 am]
BILLING CODE 4164-01-P