Document ID: FDA-2013-D-0349-0012
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposed Collection;  Comment Request; Providing Waiver-Related Materials in Accordance With  the Guidance for Industry on Providing Post-Market Periodic Safety Reports in the International Conference on Harmonisation E2C(R2) Format
Posted Date: 2017-05-23T04:00Z

[Federal Register Volume 82, Number 98 (Tuesday, May 23, 2017)]
[Notices]
[Pages 23578-23581]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-10537]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-0349]

Agency Information Collection Activities; Proposed Collection; 
Comment Request; Providing Waiver-Related Materials in Accordance With 
the Guidance for Industry on Providing Post-Market Periodic Safety 
Reports in the International Conference on Harmonisation E2C(R2) Format

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) 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 the collection of information associated 
with the Guidance ``Providing Post-market Periodic Safety Reports in 
the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report).''

DATES: Submit either electronic or written comments on the collection 
of information by July 24, 2017. Late, untimely filed comments will not 
be considered. Electronic comments must be submitted on or before July 
24, 2017. The https://www.regulations.gov electronic filing system will 
accept comments until midnight Eastern Time at the end of July 24, 
2017. 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.

ADDRESSES: You may submit comments as follows:

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

[[Page 23579]]

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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-D-0349 for ``Providing Waiver-Related Materials in Accordance 
With the Guidance for Industry on Providing Post-market Periodic Safety 
Reports in the International Conference on Harmonisation E2C(R2) 
Format.'' Received comments, those filed in a timely manner (see 
DATES), will be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Division of Dockets Management 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 Division of Dockets Management. 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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A63, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), 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.

Providing Waiver-Related Materials in Accordance With the Guidance for 
Industry on Providing Post-Market Periodic Safety Reports in the 
International Conference on Harmonisation E2C(R2) Format (Periodic 
Benefit-Risk Evaluation Report), OMB Control Number 0910-0771--
Extension

    The International Conference on Harmonisation (ICH) of Technical 
Requirements for Registration of Pharmaceuticals for Human Use issued, 
on November 15, 2012, the ICH harmonized tripartite guideline entitled 
``Periodic Benefit-Risk Evaluation Report (PBRER) E2C(R2)'' (the PBRER 
guideline) (available at http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html). The PBRER guideline is 
intended to promote a consistent approach to periodic post-marketing 
safety reporting among the ICH regions and to enhance efficiency by 
reducing the number of reports generated for submission to the 
regulatory authorities. The PBRER is intended to provide a common 
standard for periodic reporting on approved drugs or biologics among 
the ICH regions.
    FDA currently has OMB approval for the required submission of 
periodic adverse drug experience reports (PADER) for drugs subject to a 
new drug application (NDA) or an abbreviated new drug application 
(ANDA) (Sec.  [thinsp]314.80(c)(2) (21 CFR 314.80(c)(2)) (OMB control 
number 0910-0230), and for the required submission of periodic adverse 
experience reports (PAER) for drugs subject to a biologics license 
application (BLA) (Sec.  [thinsp]600.80(c)(2) (21 CFR 600.80(c)(2)) 
(OMB control number 0910-0308).
    There is considerable overlap in the information required under 
Sec. Sec.  [thinsp]314.80(c)(2) and 600.80(c)(2) and the information 
requested in a periodic safety report using the ICH E2C(R2) PBRER 
format. Applicants subject to periodic safety reporting requirements 
under FDA regulations could choose to continue to submit the reports as 
specified in those regulations, and would be permitted to submit 
reports in the PBRER format and submit reports as specified in FDA 
regulations with an approved waiver. Companies who submit periodic 
reports on the same drug to multiple regulators, including not only the 
United States, but, also the European Union, Japan, and regulators in 
other countries who have elected to adopt the ICH standards, may find 
it in their interest to prepare a single PBRER,

[[Page 23580]]

rather than preparing multiple types of reports for multiple 
regulators. As a result, FDA, in the Federal Register of November 29, 
2016 (81 FR 85976), announced the availability of the guidance for 
industry entitled ``Providing Post-marketing Periodic Safety Reports in 
the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report)'' to 
indicate its willingness to accept post-market periodic safety reports 
using the ICH PBRER format in lieu of the specific reports described in 
FDA regulations.
    Because FDA regulations in Sec. Sec.  [thinsp]314.80(c)(2) and 
600.80(c)(2) include specific requirements for periodic safety reports, 
in order for an applicant to submit an alternative report, such as the 
PBRER, for a given product, FDA must grant a waiver. Existing 
regulations permit applicants to request waivers of any post-marketing 
safety reporting requirement, and the information collections 
associated with such waiver requests generally are approved under 
existing control numbers. (See Sec.  [thinsp]314.90(a), waivers for 
drugs subject to NDAs and ANDAs, approved under OMB control number 
0910-0001, and Sec.  [thinsp]600.90(a), waivers for products subject to 
BLAs, approved under OMB control number 0910-0308.) The November 29, 
2016, guidance both explains conditions under which applicants that 
have previously received waivers to submit reporting information in the 
format of the previous ICH guidance would be permitted to apply those 
existing waivers to the submission of PBRERs, and also advises how 
applicants that have not previously obtained a waiver may submit waiver 
requests to submit the PBRER.
    There are information collections proposed in the November 29, 
2016, guidance that are related to waivers specifically to enable the 
submission of PBRERs, and these information collections are not already 
addressed under the approved control numbers covering waiver 
submissions and periodic safety reports generally. FDA has previously 
granted waiver requests, submitted under Sec. Sec.  [thinsp]314.90(a) 
and 600.90(a), that allow applicants to prepare and submit reports 
using the periodic safety update report (PSUR) format described in 
FDA's 1996 and 2004 ICH E2C guidance. In accordance with the 
recommendations of the November 29, 2016, guidance, if an applicant 
already has a PSUR waiver in place for a given approved application, 
FDA will consider the existing PSUR waiver to allow the applicant to 
submit a PBRER instead of a PSUR because the PBRER replaces the PSUR 
for post-marketing periodic safety reporting for that application. The 
applicant would not need to submit a new waiver request unless the 
applicant wishes to change the frequency of reporting. FDA will 
consider requests to be waived of the quarterly reporting requirement 
but will not waive applicants of the annual reporting requirement.
    If an applicant submits a PBRER in place of the PSUR and uses a 
different data lock point, the applicant should submit overlapping 
reports or submit a one-time PADER/PAER in order to cover the gap in 
reporting intervals. The applicant should submit notification to the 
application(s), indicating the change in data lock point and should 
include a description of the measures taken to ensure that there are no 
resulting gaps in reporting.
    If an applicant submits a PBRER in place of the PSUR and uses a 
different reporting frequency for the PBRER than was used for the PSUR, 
the continued validity of the waiver will be conditioned on the 
submission of a PADER/PAER as needed to fulfill the reporting frequency 
requirement under FDA regulations. The applicant should submit a 
notification to the application(s), describing this change and the 
measures taken to ensure that the periodicity requirements are being 
met.
    FDA expects approximately 187 waiver requests and notifications to 
include the additional information described previously in this 
document for using a different data lock point and/or for using a 
different reporting frequency when submitting a PBRER. FDA expects 
approximately 55 applicants to make these submissions, and we estimate 
that the time for submitting the additional information described 
previously would be on average approximately 1 hour for each waiver 
request or notification.
    If an applicant does not have a PSUR waiver in place for an 
approved application, the applicant may submit a waiver request under 
Sec.  [thinsp]314.90(a) or Sec.  [thinsp]600.90(a) to submit a PBRER 
instead of the PADER/PAER. The applicant should submit a request to FDA 
for each approved application for which a waiver is requested, and a 
single waiver request letter can include multiple applications. Waiver 
requests should be submitted to each of the application(s) in the 
request, and may be submitted electronically or by mail as described in 
the November 29, 2016, guidance. Each PBRER waiver request should 
include the following information:
     The product name(s) and application number(s);
     a brief description of the justification for the request;
     the U.S. approval date for the product(s) and current 
reporting interval used;
     the reporting interval of the last PADER/PAER submitted 
for the product(s); and
     the data lock point that will be used for each PBRER. If a 
data lock point other than one aligned to the U.S. approval date is 
proposed, the applicant should describe how he/she will ensure that 
there are no gaps in reporting intervals (e.g., by submitting 
overlapping reports; submitting a one-time PADER/PAER to cover the gap 
period; or, if the gap is less than 2 months, extending the reporting 
interval of the final PADER/PAER to close the gap).
     The frequency for submitting the PBRER, as described in 
section IV.C of the April 8, 2013, draft guidance.
     The email address and telephone number for the individual 
who can provide additional information regarding the waiver request.
    As explained earlier, existing regulations at Sec.  314.90(a) or 
600.90(a) permit applicants to request waivers of any post-marketing 
safety reporting requirement, and the information collections 
associated with such waiver requests generally are approved under OMB 
control numbers 0910-0001 and 0910-0308. FDA believes that the 
information submitted under numbers 1-4 and number 7 in the list in the 
previous paragraph is information that is typical of any waiver request 
regarding post-marketing safety reporting and is accounted for in the 
existing approved collections of information for waiver requests and 
reports. Concerning numbers 5 and 6, FDA expects approximately 67 
waiver requests to include the additional information for using a 
different data lock point and/or for using a different reporting 
frequency when submitting a PBRER. FDA expects approximately 29 
applicants to make these submissions, and we estimate that the time for 
submitting the additional information described in the previous 
paragraph would be on average approximately 2 hours for each waiver 
request.
    FDA estimates the additional burden of this collection of 
information as follows:

[[Page 23581]]

                                     Table 1--Estimated Reporting Burden \1\
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  Additional information and/or
    notifications for using a        Number of       Number of     Total annual       Average
different data lock point and/or    respondents    responses per     responses      burden per      Total hours
a different reporting  frequency                    respondent                       response
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Applicants that have a PSUR                   55             3.4             187               1             187
 waiver for an approved
 application....................
Applicants that do not have a                 29             2.3              67               2             134
 PSUR waiver for an approved
 application....................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............             321
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\1\ There are no capital or operating and maintenance costs associated with the information collection.

    Dated: May 18, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-10537 Filed 5-22-17; 8:45 am]
 BILLING CODE 4164-01-P