[Federal Register Volume 84, Number 206 (Thursday, October 24, 2019)]
[Notices]
[Pages 57030-57034]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-23204]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0825]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Premarket Approval of Medical Devices

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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[[Page 57031]]

SUMMARY: The Food and Drug Administration (FDA or Agency) 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 requirements for premarket approval of 
medical devices.

DATES: Submit either electronic or written comments on the collection 
of information by December 23, 2019.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before December 23, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of December 23, 2019. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is 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-2013-N-0825 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Premarket Approval of Medical 
Devices.'' 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.
     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.gpo.gov/fdsys/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.

FOR FURTHER INFORMATION CONTACT: Amber Sanford, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-8867, 
PRAStaff@fda.hhs.gov.

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 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.

Premarket Approval of Medical Devices

OMB Control Number 0910-0231--Extension

    Under section 515 of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 360e) all devices placed into class III by FDA are 
subject to

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premarket approval application (PMA) requirements. PMA is the process 
of scientific and regulatory review to ensure the safety and 
effectiveness of class III devices. An approved PMA is, in effect, a 
private license granted to the applicant for marketing a particular 
medical device. A class III device that fails to meet PMA requirements 
is considered to be adulterated under section 501(f) of the FD&C Act 
(21 U.S.C. 351(f)) and cannot be marketed. PMA requirements apply 
differently to preamendments devices, postamendments devices, and 
transitional class III devices.
    Manufacturers of class III preamendments devices (devices that were 
in commercial distribution before May 28, 1976) are not required to 
submit a PMA until 30 months after the issuance of a final 
classification regulation or until 90 days after the publication of a 
final regulation requiring the submission of a PMA, whichever period is 
later. FDA may allow more than 90 days after issuance of a final rule 
for submission of a PMA.
    A postamendments device is one that was first distributed 
commercially on or after May 28, 1976. Postamendments devices 
determined by FDA to be substantially equivalent to preamendments class 
III devices are subject to the same requirements as the preamendments 
devices. FDA determines substantial equivalence after reviewing an 
applicant's premarket notification submitted in accordance with section 
510(k) of the FD&C Act (21 U.S.C. 360(k)). Postamendments devices 
determined by FDA to be not substantially equivalent to either 
preamendments devices or postamendments devices classified into class I 
or II are ``new'' devices and fall automatically into class III. Before 
such devices can be marketed, they must have an approved PMA or be must 
reclassified into class I or class II.
    The Food and Drug Administration Modernization Act of 1997 (FDAMA) 
(Pub. L. 105-115) amended the FD&C Act by streamlining the process of 
bringing safe and effective drugs, medical devices, and other therapies 
to the U.S. market. FDAMA added section 515(d)(6) to the FD&C Act, 
which provided that PMA supplements were required for all device 
changes that affect safety and effectiveness unless such changes are 
modifications to manufacturing procedures or method of manufacture. 
That type of manufacturing change requires a 30-day notice, or where 
FDA finds such notice inadequate, a 135-day PMA supplement.
    The implementing regulations, contained in 21 CFR part 814, further 
specify the contents of a PMA for a medical device and the criteria FDA 
will employ in approving, denying, or withdrawing approval of a PMA and 
supplements to PMAs. The regulations' purpose is to establish an 
efficient and thorough procedure for FDA's review of PMAs and 
supplements to PMAs for class III medical devices. The regulations 
facilitate the approval of PMAs and supplements to PMAs for devices 
that have been shown to be reasonably safe and effective and otherwise 
meet the statutory criteria for approval. The regulations also allow 
for the denial of PMAs and supplements to PMAs for devices that have 
not been shown to be reasonably safe and effective and that do not 
otherwise meet the statutory criteria for approval.
    The burden estimate is based on the annual rate of receipt of PMA 
submissions for fiscal years (FYs) 2016 through 2018 and our 
expectation of submissions to come in the next few years. The burden 
data for PMAs is based on data provided by applicants by device type 
and cost element in an earlier study.

Reporting Burden

    Section 814.15(b) (21 CFR 814.15(b))--Research Conducted Outside 
the United States. FDA will accept information on a clinical 
investigation conducted outside the United States (OUS) to support a 
PMA if the investigation is well-designed and well-conducted and 
certain other conditions are met, including that the investigation was 
conducted in accordance with good clinical practice (GCP) as specified 
in 21 CFR 812.28. If the OUS clinical investigation did not conform to 
GCP, then the PMA submission should include a waiver request or a 
statement explaining the reason for not conducting the investigation in 
accordance with GCP and a description of steps taken to ensure that the 
data and results are credible and accurate and that the rights, safety, 
and well-being of subjects have been adequately protected. Based on the 
number of PMAs received that contained studies from overseas, FDA 
estimates that the burden estimate necessary to meet this requirement 
is 50 hours.
    Section 814.20 (21 CFR 814.20)--Application. Specifies the 
information required in a PMA and update reports such as the 
applicant's name and address, a description of the device, its 
labeling, its indications for use, and summary of clinical and non-
clinical studies. Included in this requirement is the conduct of 
laboratory and clinical trials, as well as the analysis, review, and 
physical preparation of the PMA application. FDA estimates that 38 
applicants, including hospital remanufacturers of single-use devices, 
will be affected by these requirements, which are based on the actual 
average of FDA receipt of new PMA applications in FYs 2016 through 
2018.
    Additionally, the ``Human Subject Protection; Acceptance of Data 
from Clinical Investigations for Medical Devices'' final rule (83 FR 
7366; February 21, 2018) amended this section to address requirements 
for a PMA supported by data from clinical investigations conducted 
outside the United States. The applicant will be required to submit the 
information as described in Sec.  814.20(b)(6)(ii)(C). We estimate this 
will take 30 minutes per respondent. We estimate that 10 respondents 
annually will submit such information.
    The collections in OMB control number 0910-0741, ``Human Subject 
Protection; Acceptance of Data from Clinical Studies for Medical 
Devices,'' were submitted to OMB as a new information collection 
request with the expectation that the currently approved requirements 
will be amended. As noted in the Supporting Statement for OMB control 
number 0910-0741, we are amending OMB control number 0910-0231 to 
reflect the information collections associated with the rulemaking 
under Sec.  814.20(b)(6)(ii)(C).
    Section 814.37(a) through (c) and (e) (21 814.37(a) through (c) and 
(e))--PMA Amendments and Resubmitted PMAs. As part of the review 
process, FDA often requests the PMA applicant to submit additional 
information regarding the device necessary for FDA to file the PMA or 
to complete its review and make a final decision. The PMA applicant 
may, on their own initiative, submit additional information to FDA 
during the review process. These amendments contain information ranging 
from additional test results and reanalysis of the original data set to 
revised device labeling. Almost all PMAs received by the Agency have 
amendments submitted during the review process.
    Section 814.39(a) (21 CFR 814.39(a))--PMA Supplements. This 
information collection includes the requirements for the range of PMA 
supplements (panel track, 180-day fee-based, 180-day non-fee-based, and 
real-time supplements).
    Section 814.39(d)--Special PMA Supplements--Changes Being Affected. 
This type of supplement is intended to enhance the safety of the device 
or the safe use of the device. The number of PMA supplements received 
that fit this

[[Page 57033]]

category averaged 75 per year based on the numbers received from FYs 
2016 through 2018.
    Section 814.39(f)--30-Day Notice. Under section 515(d) of the FD&C 
Act, modifications to manufacturing procedures or methods of 
manufacture that affect the safety and effectiveness of a device 
subject to an approved PMA do not require submission of a PMA 
supplement under paragraph (a) of that section and are eligible to be 
the subject of a 30-day notice. A 30-day notice shall describe in 
detail the change, summarize the data or information supporting the 
change, and state that the change has been made in accordance with the 
requirements of part 820 (21 CFR part 820). The applicant may 
distribute the device 30 days after the date on which FDA receives the 
30-day notice, unless FDA notifies the applicant within 30 days from 
receipt of the notice that it is not adequate.
    Section 814.82(a)(9) (21 CFR 814.82(a)(9))--Postapproval 
Requirements. Postapproval requirements concerns approved PMAs that 
were not reclassified and require a periodic report. After approval, 
all PMAs require a submission of an annual report. A majority of the 
submitted PMAs require associated postapproval studies, i.e., followup 
of patients used in clinical trials to support the PMA or additional 
preclinical information that is labor-intensive to compile and 
complete; the remaining PMAs require minimal information.
    Section 814.84(b) (21 CFR 814.84(b))--Periodic Reports. 
Postapproval requirements described in Sec.  814.82(a)(7) require 
submission of an annual report for each approved PMA. FDA estimates 
that respondents will average about 10 hours in preparing their reports 
to meet this requirement. This estimate is based on FDA's experience 
and consultation with industry.
    The Breakthrough Devices Program--The Breakthrough Devices Program 
supersedes the Expedited Access Pathway and Priority Review for medical 
devices. The guidance document ``Breakthrough Devices Program'' 
implements section 515B of the FD&C Act (21 U.S.C. 360e-3), as created 
by section 3051 of the 21st Century Cures Act (Pub. L. 114-255) and 
amended by section 901 of the FDA Reauthorization Act of 2017 (Pub. L. 
115-52). The Breakthrough Devices Program is a voluntary program for 
certain medical devices and device-led combination products that 
provide for more effective treatment or diagnosis of life-threatening 
or irreversibly debilitating diseases or conditions. The program is 
intended to help patients have more timely access to these medical 
devices by expediting their development, assessment, and review, while 
preserving the statutory standards for premarket approval, 510(k) 
clearance, and De Novo marketing authorization, consistent with the 
Agency's mission to protect and promote public health.
    Agreement Meeting--Section 520(g)(7) of the FD&C Act (21 U.S.C. 
360j(g)(7)). Applicants planning to submit a PMA may submit a written 
request to reach agreement with FDA on the key parameters of the 
investigational plan.
    Determination Meeting--Section 513(a)(3)(D) of the FD&C Act (21 
U.S.C. 360c(a)(3)(D)). Applicants planning to submit a PMA may submit a 
written request to FDA for a meeting to determine the type of 
information (valid scientific evidence) necessary to support the 
effectiveness of their device.
    Panel of Experts--Section 515(c)(3) of the FD&C Act. An original 
PMA or panel track PMA supplement is taken to an advisory panel of 
experts unless FDA determines that the information in the application 
substantially duplicates information that has previously been reviewed 
by the panel.
    Day 100 Meeting--Section 515(d)(3) of the FD&C Act. FDA must, upon 
the written request of the applicant, meet with that party within 100 
days of receipt of the filed PMA application to discuss the review 
status of the application. With the concurrence of the applicant, a 
different schedule may be established. Prior to this meeting, FDA must 
inform the applicant in writing of any identified deficiencies and what 
information is required to correct those deficiencies. FDA must also 
promptly notify the applicant if FDA identifies additional deficiencies 
or of any additional information required to complete Agency review.

Recordkeeping

    Section 814.82(a)(5) and (6)--Maintenance of Records. The 
recordkeeping burden under this section requires the maintenance of 
records used to trace patients, and the organization and indexing of 
records into identifiable files to ensure the device's continued safety 
and effectiveness. These records are required of all applicants who 
have an approved PMA.
    PMAs have been required since 1976, and there are 801 active PMAs 
that could be subject to these requirements, based on actual FDA data, 
and approximately 39 new PMAs are approved every year. The aggregate 
burden for the estimated 446 PMA holders of approved original PMAs for 
the next few years is estimated to be 7,582 hours.
    The applicant determines which records should be maintained during 
product development to document and/or substantiate the device's safety 
and effectiveness. Records required by the current good manufacturing 
practices for medical devices regulation (part 820) may be relevant to 
a PMA review and may be submitted as part of an application. In 
individual instances, records may be required as conditions of approval 
to ensure the device's continuing safety and effectiveness.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of                        Average
   Activity/21 CFR or FD&C Act       Number of     responses per    Total annual    burden per      Total hours
             Section                respondents     respondent       responses       response
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Research conducted outside the                25               1              25               2              50
 United States (814.15(b))......
PMA application (814.20)........              46               1              46             668          30,728
Information on clinical                       10               1              10             0.5               5
 investigations conducted
 outside the United States
 (814.20(b)(6)(ii)(C))..........
PMA amendments and resubmitted             1,528               1           1,528             167         255,176
 PMAs (814.37(a)-(c) and (e))...
PMA supplements (814.39(a)).....             777               1             777              60          46,620
Special PMA supplement--changes               75               1              75               6             450
 being effected (814.39(d)).....
30-day notice (814.39(f)).......           1,722               1           1,722              16          27,552
Postapproval requirements                    121               1             121             135          16,335
 (814.82(a)(9)).................

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Periodic reports (814.84(b))....             764               1             764              10           7,640
Breakthrough Devices Program                  11               1              11              10             110
 (515(B) of the FD&C Act).......
Agreement meeting (520(g)(7) of                1               1               1              50              50
 the FD&C Act)..................
Determination Meeting                          1               1               1              50              50
 (513(a)(3)(D) of the FD&C Act).
Panel meeting (515(c)(3) of the                1               1               1              30              30
 FD&C Act)......................
Day 100 meeting (515(d)(3) of                 14               1              14              10             140
 the FD&C Act)..................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............         384,936
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                                                   Table 2--Estimated Annual Recordkeeping Burden \1\
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                                                                                         Number of                      Average  burden
                      Activity/21 CFR section                           Number of       records per      Total annual         per          Total Hours
                                                                      recordkeepers     recordkeeper       records       recordkeeping
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Maintenance of records (814.82(a)(5) and (6))......................             446                1              446               17            7,582
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    We made the following changes to the information collection:
     Added the burden estimate for ``Information on clinical 
investigations conducted outside the United States 
(814.20(b)(6)(ii)(C)),'' which is associated with the ``Human Subject 
Protection; Acceptance of Data from Clinical Investigations for Medical 
Devices'' final rule as described previously in this document.
     Revised the burden description and table to reflect that 
the Expedited Access Pathway and Priority Review have been superseded 
by the Breakthrough Devices Program.
     Updated our burden estimate with FYs 2016 to 2018 data.
    These adjustments resulted in an overall increase of 34,782 hours 
to the estimated burden.

    Dated: October 15, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-23204 Filed 10-23-19; 8:45 am]
 BILLING CODE 4164-01-P


