Agency Information Collection Activities; Proposed Collection; Comment Request; Providing Waiver-Related Materials in Accordance With Draft Guidance for Industry on Providing Postmarket Periodic Safety Reports in the International Conference on Harmonisation E2C(R2) Format, 74151-74154 [2013-29393]
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Federal Register / Vol. 78, No. 237 / Tuesday, December 10, 2013 / Notices
Dated: December 3, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
reporting requirements in FDA
regulations.
Submit either electronic or
written comments on the collection of
information by February 10, 2014.
DATES:
[FR Doc. 2013–29394 Filed 12–9–13; 8:45 am]
BILLING CODE 4160–01–P
Food and Drug Administration
[Docket No. FDA–2013–D–1478]
Agency Information Collection
Activities; Proposed Collection;
Comment Request; Providing WaiverRelated Materials in Accordance With
Draft Guidance for Industry on
Providing Postmarket Periodic Safety
Reports in the International
Conference on Harmonisation E2C(R2)
Format
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
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 (the
PRA), Federal Agencies are required to
publish notice in the Federal Register
concerning each proposed collection of
information and to allow 60 days for
public comment in response to the
notice. This notice solicits comments on
the information collection associated
with the submission of periodic safety
reports as described in the guidance
entitled ‘‘Periodic Benefit-Risk
Evaluation Report (PBRER) (E2C(R2)).’’
The guidance was prepared under the
auspices of the International Conference
on Harmonisation (ICH) of Technical
Requirements for Registration of
Pharmaceuticals for Human Use, and
describes the format, content, and
timing of a PBRER for an approved drug
or biologic. This notice also solicits
comments on the information collection
associated with the submission of
waiver-related materials as described in
the draft guidance entitled ‘‘Providing
Postmarket Periodic Safety Reports in
the ICH E2C(R2) Format.’’ The draft
guidance is intended to inform
applicants of the conditions under
which FDA will exercise its waiver
authority to permit applicants to submit
an ICH E2C(R2) PBRER in place of the
ICH E2C(R1) Periodic Safety Update
Report (PSUR), U.S. periodic adverse
drug experience report (PADER), or U.S.
periodic adverse experience report
(PAER), to satisfy the periodic safety
maindgalligan on DSK5TPTVN1PROD with NOTICES
SUMMARY:
18:48 Dec 09, 2013
FDA
PRA Staff, Office of Operations, Food
and Drug Administration,1350 Piccard
Dr.,PI50–400B, Rockville, MD 20850,
PRAStaff@fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
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
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.
SUPPLEMENTARY INFORMATION:
Notice.
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Submit electronic
comments on the collection of
information to https://
www.regulations.gov. Submit written
comments on the collection of
information to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane., Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
docket number found in brackets in the
heading of this document.
ADDRESSES:
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
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74151
Reporting in Accordance With
International Conference on
Harmonisation—Periodic Benefit-Risk
Evaluation Report (E2C(R2)) Guidance
I. Background
ICH was organized to provide an
opportunity for tripartite harmonization
initiatives to be developed with input
from both regulatory and industry
representatives. ICH is concerned with
harmonization of technical
requirements for the registration of
pharmaceutical products among three
regions: The European Union, Japan,
and the United States. In January 2012,
the ICH Steering Committee agreed that
the ‘‘E2C(R2) Periodic Benefit-Risk
Evaluation Report’’ draft guidance (the
draft PBRER guidance) should be made
available for public comment. The
PBRER is intended to provide a
common standard for periodic reporting
on approved drugs or biologics among
the ICH regions. The harmonized
PBRER is intended to promote a
consistent approach to periodic
postmarket safety reporting among the
ICH regions and to enhance efficiency
by reducing the number of reports
generated for submission to the
regulatory authorities.
The draft PBRER guidance revises an
earlier version of this guidance issued in
1997 with an addendum issued in 2004.
In the Federal Register of April 11, 2012
(77 FR 21782), FDA announced the
availability of the draft PBRER guidance
for public comment. FDA presented the
comments received as part of the
considerations by the E2C(R2) Expert
Working Group for revisions of the
guidance. A final version of the
guidance was subsequently endorsed by
the ICH on November 15, 2012, and
published as the ICH harmonized
tripartite guideline ‘‘Periodic BenefitRisk Evaluation Report (PBRER)
E2C(R2)’’ (the PBRER guidance),
available at https://www.ich.org/
products/guidelines/efficacy/article/
efficacy-guidelines.html. FDA
anticipates issuing final guidance on
this topic that is consistent with the
final ICH document, published
November 2012, and thus is seeking
PRA approval for information
collections consistent with that
document.
The April 11, 2012, Federal Register
notice stated that the draft PBRER
guidance includes information
collection provisions that are subject to
review by OMB under the PRA, and that
before publication of the final guidance
document, FDA intends to solicit public
comment and obtain OMB approval for
any information collections
recommended in the guidance that are
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new or that would represent material
modifications to previously approved
collections of information found in FDA
regulations. This Federal Register
notice begins the process of requesting
public comment and obtaining OMB
approval for collections of information
associated with reporting in accordance
with the PBRER guidance.
II. Voluntary Preparation of Periodic
Safety Reports in Conformance With the
ICH E2C(R2) PBRER Guidance, in Lieu
of PADERs/PAERs Required Under 21
CFR 314.80(c)(2) and 600.80(c)(2)
FDA currently has OMB approval for
the required submission of PADERs for
drugs subject to a new drug application
(NDA) or an abbreviated new drug
application (ANDA) (§ 314.80(c)(2) (21
CFR 314.80(c)(2)); OMB control number
0910–0230), and for the required
submission of PAERs for drugs subject
to a biologics license application (BLA)
(§ 600.80(c)(2) (21 CFR 600.80(c)(2));
OMB control number 0910–0308). Such
reports include, for the reporting
interval, reports of serious, expected
adverse experiences and all non-serious
adverse experiences and an index of
these reports, a narrative summary and
analysis of adverse experiences, an
analysis of the 15-day Alert reports
submitted during the reporting interval,
and a history of actions taken because
of adverse experiences. Applicants must
submit each PADER/PAER to FDA
quarterly for the first 3 years after the
product is approved by FDA and
annually thereafter. As described in the
supporting documentation under OMB
control numbers 0910–0230 and 0910–
0308, FDA currently has OMB approval
for approximately 60 hours for the
preparation and submission of each
PADER under § 314.80(c)(2) and 28
hours for the preparation and
submission of each PAER under
§ 600.80(c)(2).
There is considerable overlap in the
information required under
§§ 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. As a result, and as
discussed further in this document,
FDA, in the Federal Register of April 8,
2013 (78 FR 20926), announced the
availability of a draft guidance to
indicate its willingness to accept
postmarket periodic safety reports using
the ICH PBRER format in lieu of the
specific reports described in FDA
regulations. (As described further in this
document, the April 2013 draft
guidance also addresses waiver-related
information that should be submitted to
FDA by companies who wish to exercise
this alternative reporting.)
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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,
rather than preparing multiple types of
reports for multiple regulators.
Companies who choose to submit a
PBRER to FDA would include some
information beyond that required by
FDA regulations, including worldwide
marketing approval status; estimated
exposure and use patterns; information
from clinical trials, non-interventional
studies, non-clinical data, and literature;
benefit evaluation, and benefit-risk
analysis for approved indications, and
should use a particular format described
in that guidance.
FDA is not proposing to require
submission of the PBRER; 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 alternate
between submission of reports in the
PBRER format and submission of reports
as specified in FDA regulations with an
approved waiver. Based on FDA’s
experience with submission of periodic
safety reports under previous ICH
periodic reporting guidance, FDA
believes that applicants would elect to
submit the PBRER to FDA only in cases
where they are also submitting that
report to other regulatory authorities,
some of which have underlying legal
requirements that closely parallel the
elements of the PBRER. For this reason,
FDA believes that the additional burden
associated with preparation of a PBRER
in lieu of existing PADERs/PAERs is not
attributable to the proposed collection
of information by FDA, but rather is a
‘‘usual and customary’’ expenditure of
time, effort, and financial resources that
would be ‘‘incurred by persons in the
normal course of their activities,’’ and
thus is excluded from the calculation of
burden under the PRA (5 CFR
1320.5(b)(2).) Cf. 5 CFR 1320.5(b)(3)
(permitting exclusion from Federal
burden of burden incurred in complying
with an information collection that is
also conducted by a State or local
government if the State or local
requirement would be imposed even in
the absence of a Federal requirement).
We therefore believe that the existing
estimate of burden for submission of
periodic safety reports, approved under
OMB control numbers 0910–0230 and
0910–0308, would be unchanged by this
proposed collection, which would
permit, but not require, the substitution
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of a PBRER for the periodic safety report
otherwise required. We request
comment on the assumption that all
PBRERs submitted to FDA would be
prepared in any event to submit to other
jurisdictions, or alternatively, on the
number of PBRERs that applicants will
choose to prepare solely for submission
to FDA, and the estimated burden for
submitting such a report.
III. Materials Related to Waivers
Permitting Submission of a PBRER To
Satisfy the Periodic Safety Reporting
Requirements in §§ 314.80(c)(2) and
600.80(c)(2)
Because FDA regulations in
§§ 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 postmarketing safety reporting
requirement, and the information
collections associated with such waiver
requests generally are approved under
existing control numbers. (See
§ 314.90(a), waivers for drugs subject to
NDAs and ANDAs (approved under
OMB control number 0910–0001); and
§ 600.90(a), waivers for products subject
to BLAs (approved under OMB control
number 0910–0308).)
In the Federal Register of April 8,
2013, FDA announced the availability of
a draft guidance entitled ‘‘Providing
Postmarket Periodic Safety Reports in
the ICH E2C(R2) Format,’’ which
indicates that FDA will be prepared to
grant waivers to enable submission of
the PBRER in the United States in place
of a PADER required under
§ 314.80(c)(2) or in place of a PAER
required under § 600.80(c)(2). The draft
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 that would
be granted for the submission of
PBRERs. This Federal Register notice
solicits comment on certain information
collections proposed in the April 8,
2013, draft guidance that are related to
waivers specifically to enable the
submission of PBRERs, and that are not
already addressed under approved
control numbers covering waiver
submissions and periodic safety reports
generally.
FDA has previously granted waiver
requests, submitted under §§ 314.90(a)
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and 600.90(a), that allow applicants to
prepare and submit reports using the
PSUR format described in the 1997 and
2004 ICH E2C guidance. In accordance
with the recommendations of the April
8, 2013, draft 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 postmarketing
periodic safety reporting for that
application. The applicant would not
need to submit a new waiver request
unless the applicant wishes to use a
different data lock point or change the
frequency of reporting.
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 request a waiver to
change the data lock point and this
waiver request should include a
description of the measures taken to
ensure that there are no resulting gaps
in reporting with the change.
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 applicant
must request a waiver. This waiver
request should describe the measures
taken to ensure that the periodicity
requirements under §§ 314.80(c)(2)(i)
and 600.80(c)(2)(i) are being met. If an
applicant requests to submit a PBRER
less frequently than is permitted under
the applicant’s PSUR waiver, 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 draft guidance
also states that if an applicant is on a
quarterly reporting schedule but wishes
to submit a PBRER every 6 months
without submitting a quarterly PADER/
PAER in the intervening quarters, the
applicant may request a waiver of the
quarterly reporting requirement.
FDA expects approximately 189
waiver requests to include the
additional information and notifications
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
and notifications described previously
would be on average approximately 1
hour for each waiver request.
If an applicant does not have a PSUR
waiver in place for an approved
application, the applicant may submit a
waiver request under § 314.90(a) or
§ 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 April 8, 2013, draft guidance. Each
PBRER waiver request should include
the following information:
(1) The product name(s) and
application number(s);
(2) A brief description of the
justification for the request;
(3) The U.S. approval date for the
product(s) and current reporting interval
used;
(4) The reporting interval of the last
PADER/PAER submitted for the
product(s);
(5) 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 onetime 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).
(6) The frequency for submitting the
PBRER, as described in section IV.C of
the April 8, 2013, draft guidance.
(7) The email address and telephone
number for the individual who can
provide additional information
regarding the waiver request.
As explained earlier, existing
regulations at §§ 314.90(a) or 600.90(a)
permit applicants to request waivers of
any postmarketing safety reporting
requirement, and the information
collections associated with such waiver
requests generally are approved under
OMB control numbers 0910–0001and
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 postmarketing 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:
TABLE 1—ESTIMATED REPORTING BURDEN 1
Additional information and/or notifications for using a
different data lock point and/or a different reporting
frequency
Number of
respondents
Number of
responses per
respondent
Total annual
responses
Average
burden per
response
Total hours
maindgalligan on DSK5TPTVN1PROD with NOTICES
Applicants that have a PSUR waiver for an approved application ............................................................................
Applicants that do not have a PSUR waiver for an approved application ............................................................
55
3.4
187
1
187
29
2.3
67
2
134
Total ..............................................................................
........................
........................
........................
........................
321
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
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74154
Federal Register / Vol. 78, No. 237 / Tuesday, December 10, 2013 / Notices
Dated: December 3, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
Rockville Pike, Rockville, MD 20852,
240–402–3861; or Vilayat Sayeed,
Center for Drug Evaluation and Research
(HFD–630), Food and Drug
Administration, 7520 Standish Pl.,
Rockville, MD 20855, 240–276–8486.
[FR Doc. 2013–29393 Filed 12–9–13; 8:45 am]
BILLING CODE 4160–01–P
SUPPLEMENTARY INFORMATION:
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
I. Background
Food and Drug Administration
[Docket No. FDA–2013–N–1434]
Draft Guidance for Industry on Size,
Shape, and Other Physical Attributes
of Generic Tablets and Capsules;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance for
industry entitled ‘‘Size, Shape, and
Other Physical Attributes of Generic
Tablets and Capsules.’’ This guidance
discusses FDA recommendations for the
size, shape, and other physical
attributes of generic tablets intended to
be swallowed intact. FDA is concerned
that these characteristics of generic
drugs are too varied compared to the
originator drug and could affect patient
outcomes.
DATES: Although you can comment on
any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency
considers your comment on this draft
guidance before it begins work on the
final version of the guidance, submit
either electronic or written comments
on the draft guidance by March 10,
2014.
SUMMARY:
Submit written requests for
single copies of the draft guidance to the
Division of Drug Information, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 2201,
Silver Spring, MD 20993–0002. Send
one self-addressed adhesive label to
assist that office in processing your
requests. See the SUPPLEMENTARY
INFORMATION section for electronic
access to the draft guidance document.
Submit electronic comments on the
draft guidance to https://
www.regulations.gov. Submit written
comments to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Debra Catterson, Center for Drug
Evaluation and Research (HFD–600),
Food and Drug Administration, 11919
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ADDRESSES:
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FDA is announcing the availability of
a draft guidance for industry entitled
‘‘Size, Shape, and Other Physical
Attributes of Generic Tablets and
Capsules.’’ FDA is concerned that the
differences in size, shape, and other
physical characteristics between the
generic and the originator could
adversely affect patient outcomes. For
example, studies show that tablet size
can affect ease of swallowing, and
generic tablets that are significantly
larger than their corresponding
reference drug product may be more
difficult to swallow, leading to potential
adverse events as well as
noncompliance with treatment
regimens. FDA is recommending generic
manufacturers consider the size, shape,
and other physical characteristics of the
originator drug when developing a
generic version.
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
represent the Agency’s current thinking
on tablet size, shape, and other physical
attributes of generic solid oral dosage
forms. It does not create or confer any
rights for or on any person and does not
operate to bind FDA or the public. An
alternative approach may be used if
such approach satisfies the
requirements of the applicable statutes
and regulations.
II. Paperwork Reduction Act of 1995
This draft guidance contains
information collection provisions that
are subject to review by the Office of
Management and Budget (OMB) under
the Paperwork Reduction Act of 1995
(the PRA) (44 U.S.C. 3501–3520). The
collection of information requested in
the draft guidance is covered under FDA
regulations at 21 CFR 314 and approved
under OMB control number 0910–0001.
In accordance with the PRA, prior to
publication of any final guidance
document, FDA intends to solicit public
comment and obtain OMB approval for
any information collections
recommended in this guidance that are
new or that would represent material
modifications to those previously
approved collections of information
found in FDA regulations or guidances.
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III. Comments
Interested persons may submit either
electronic comments regarding this
document to https://www.regulations.gov
or written comments to the Division of
Dockets Management (see ADDRESSES). It
is only necessary to send one set of
comments. Identify comments with the
docket number found in 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 https://
www.regulations.gov.
IV. Electronic Access
Persons with access to the Internet
may obtain the document at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm or https://
www.regulations.gov.
Dated: December 2, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013–29395 Filed 12–9–13; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–D–0928]
Draft Guidance for Industry on
Recommendations for Preparation and
Submission of Animal Food Additive
Petitions; Reopening of the Comment
Period
AGENCY:
Food and Drug Administration,
HHS.
Notice; reopening of the
comment period.
ACTION:
The Food and Drug
Administration (FDA) is reopening the
comment period for the notice
published in the Federal Register of
Wednesday, September 11, 2013 (78 FR
55727), announcing the availability of
the draft guidance for industry (GFI
#221) entitled ‘‘Recommendations for
Preparation and Submission of Animal
Food Additive Petitions.’’
DATES: Submit either electronic or
written comments by January 9, 2014.
ADDRESSES: Submit electronic
comments to https://
www.regulations.gov. Submit written
comments to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Sharon Benz, Center for Veterinary
SUMMARY:
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[Federal Register Volume 78, Number 237 (Tuesday, December 10, 2013)]
[Notices]
[Pages 74151-74154]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-29393]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2013-D-1478]
Agency Information Collection Activities; Proposed Collection;
Comment Request; Providing Waiver-Related Materials in Accordance With
Draft Guidance for Industry on Providing Postmarket Periodic Safety
Reports in the International Conference on Harmonisation E2C(R2) Format
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
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
(the PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information and
to allow 60 days for public comment in response to the notice. This
notice solicits comments on the information collection associated with
the submission of periodic safety reports as described in the guidance
entitled ``Periodic Benefit-Risk Evaluation Report (PBRER) (E2C(R2)).''
The guidance was prepared under the auspices of the International
Conference on Harmonisation (ICH) of Technical Requirements for
Registration of Pharmaceuticals for Human Use, and describes the
format, content, and timing of a PBRER for an approved drug or
biologic. This notice also solicits comments on the information
collection associated with the submission of waiver-related materials
as described in the draft guidance entitled ``Providing Postmarket
Periodic Safety Reports in the ICH E2C(R2) Format.'' The draft guidance
is intended to inform applicants of the conditions under which FDA will
exercise its waiver authority to permit applicants to submit an ICH
E2C(R2) PBRER in place of the ICH E2C(R1) Periodic Safety Update Report
(PSUR), U.S. periodic adverse drug experience report (PADER), or U.S.
periodic adverse experience report (PAER), to satisfy the periodic
safety reporting requirements in FDA regulations.
DATES: Submit either electronic or written comments on the collection
of information by February 10, 2014.
ADDRESSES: Submit electronic comments on the collection of information
to https://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane., Rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations,
Food and Drug Administration,1350 Piccard Dr.,PI50-400B, Rockville, MD
20850, 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 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.
Reporting in Accordance With International Conference on
Harmonisation--Periodic Benefit-Risk Evaluation Report (E2C(R2))
Guidance
I. Background
ICH was organized to provide an opportunity for tripartite
harmonization initiatives to be developed with input from both
regulatory and industry representatives. ICH is concerned with
harmonization of technical requirements for the registration of
pharmaceutical products among three regions: The European Union, Japan,
and the United States. In January 2012, the ICH Steering Committee
agreed that the ``E2C(R2) Periodic Benefit-Risk Evaluation Report''
draft guidance (the draft PBRER guidance) should be made available for
public comment. The PBRER is intended to provide a common standard for
periodic reporting on approved drugs or biologics among the ICH
regions. The harmonized PBRER is intended to promote a consistent
approach to periodic postmarket safety reporting among the ICH regions
and to enhance efficiency by reducing the number of reports generated
for submission to the regulatory authorities.
The draft PBRER guidance revises an earlier version of this
guidance issued in 1997 with an addendum issued in 2004. In the Federal
Register of April 11, 2012 (77 FR 21782), FDA announced the
availability of the draft PBRER guidance for public comment. FDA
presented the comments received as part of the considerations by the
E2C(R2) Expert Working Group for revisions of the guidance. A final
version of the guidance was subsequently endorsed by the ICH on
November 15, 2012, and published as the ICH harmonized tripartite
guideline ``Periodic Benefit-Risk Evaluation Report (PBRER) E2C(R2)''
(the PBRER guidance), available at https://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html. FDA anticipates
issuing final guidance on this topic that is consistent with the final
ICH document, published November 2012, and thus is seeking PRA approval
for information collections consistent with that document.
The April 11, 2012, Federal Register notice stated that the draft
PBRER guidance includes information collection provisions that are
subject to review by OMB under the PRA, and that before publication of
the final guidance document, FDA intends to solicit public comment and
obtain OMB approval for any information collections recommended in the
guidance that are
[[Page 74152]]
new or that would represent material modifications to previously
approved collections of information found in FDA regulations. This
Federal Register notice begins the process of requesting public comment
and obtaining OMB approval for collections of information associated
with reporting in accordance with the PBRER guidance.
II. Voluntary Preparation of Periodic Safety Reports in Conformance
With the ICH E2C(R2) PBRER Guidance, in Lieu of PADERs/PAERs Required
Under 21 CFR 314.80(c)(2) and 600.80(c)(2)
FDA currently has OMB approval for the required submission of
PADERs for drugs subject to a new drug application (NDA) or an
abbreviated new drug application (ANDA) (Sec. 314.80(c)(2) (21 CFR
314.80(c)(2)); OMB control number 0910-0230), and for the required
submission of PAERs for drugs subject to a biologics license
application (BLA) (Sec. 600.80(c)(2) (21 CFR 600.80(c)(2)); OMB
control number 0910-0308). Such reports include, for the reporting
interval, reports of serious, expected adverse experiences and all non-
serious adverse experiences and an index of these reports, a narrative
summary and analysis of adverse experiences, an analysis of the 15-day
Alert reports submitted during the reporting interval, and a history of
actions taken because of adverse experiences. Applicants must submit
each PADER/PAER to FDA quarterly for the first 3 years after the
product is approved by FDA and annually thereafter. As described in the
supporting documentation under OMB control numbers 0910-0230 and 0910-
0308, FDA currently has OMB approval for approximately 60 hours for the
preparation and submission of each PADER under Sec. 314.80(c)(2) and
28 hours for the preparation and submission of each PAER under Sec.
600.80(c)(2).
There is considerable overlap in the information required under
Sec. Sec. 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. As a
result, and as discussed further in this document, FDA, in the Federal
Register of April 8, 2013 (78 FR 20926), announced the availability of
a draft guidance to indicate its willingness to accept postmarket
periodic safety reports using the ICH PBRER format in lieu of the
specific reports described in FDA regulations. (As described further in
this document, the April 2013 draft guidance also addresses waiver-
related information that should be submitted to FDA by companies who
wish to exercise this alternative reporting.)
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, rather than preparing multiple types of reports
for multiple regulators. Companies who choose to submit a PBRER to FDA
would include some information beyond that required by FDA regulations,
including worldwide marketing approval status; estimated exposure and
use patterns; information from clinical trials, non-interventional
studies, non-clinical data, and literature; benefit evaluation, and
benefit-risk analysis for approved indications, and should use a
particular format described in that guidance.
FDA is not proposing to require submission of the PBRER; 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 alternate between submission of
reports in the PBRER format and submission of reports as specified in
FDA regulations with an approved waiver. Based on FDA's experience with
submission of periodic safety reports under previous ICH periodic
reporting guidance, FDA believes that applicants would elect to submit
the PBRER to FDA only in cases where they are also submitting that
report to other regulatory authorities, some of which have underlying
legal requirements that closely parallel the elements of the PBRER. For
this reason, FDA believes that the additional burden associated with
preparation of a PBRER in lieu of existing PADERs/PAERs is not
attributable to the proposed collection of information by FDA, but
rather is a ``usual and customary'' expenditure of time, effort, and
financial resources that would be ``incurred by persons in the normal
course of their activities,'' and thus is excluded from the calculation
of burden under the PRA (5 CFR 1320.5(b)(2).) Cf. 5 CFR 1320.5(b)(3)
(permitting exclusion from Federal burden of burden incurred in
complying with an information collection that is also conducted by a
State or local government if the State or local requirement would be
imposed even in the absence of a Federal requirement).
We therefore believe that the existing estimate of burden for
submission of periodic safety reports, approved under OMB control
numbers 0910-0230 and 0910-0308, would be unchanged by this proposed
collection, which would permit, but not require, the substitution of a
PBRER for the periodic safety report otherwise required. We request
comment on the assumption that all PBRERs submitted to FDA would be
prepared in any event to submit to other jurisdictions, or
alternatively, on the number of PBRERs that applicants will choose to
prepare solely for submission to FDA, and the estimated burden for
submitting such a report.
III. Materials Related to Waivers Permitting Submission of a PBRER To
Satisfy the Periodic Safety Reporting Requirements in Sec. Sec.
314.80(c)(2) and 600.80(c)(2)
Because FDA regulations in Sec. Sec. 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 postmarketing safety reporting
requirement, and the information collections associated with such
waiver requests generally are approved under existing control numbers.
(See Sec. 314.90(a), waivers for drugs subject to NDAs and ANDAs
(approved under OMB control number 0910-0001); and Sec. 600.90(a),
waivers for products subject to BLAs (approved under OMB control number
0910-0308).)
In the Federal Register of April 8, 2013, FDA announced the
availability of a draft guidance entitled ``Providing Postmarket
Periodic Safety Reports in the ICH E2C(R2) Format,'' which indicates
that FDA will be prepared to grant waivers to enable submission of the
PBRER in the United States in place of a PADER required under Sec.
314.80(c)(2) or in place of a PAER required under Sec. 600.80(c)(2).
The draft 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 that would be granted for the submission of PBRERs. This
Federal Register notice solicits comment on certain information
collections proposed in the April 8, 2013, draft guidance that are
related to waivers specifically to enable the submission of PBRERs, and
that are not already addressed under approved control numbers covering
waiver submissions and periodic safety reports generally.
FDA has previously granted waiver requests, submitted under
Sec. Sec. 314.90(a)
[[Page 74153]]
and 600.90(a), that allow applicants to prepare and submit reports
using the PSUR format described in the 1997 and 2004 ICH E2C guidance.
In accordance with the recommendations of the April 8, 2013, draft
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 postmarketing periodic safety reporting for
that application. The applicant would not need to submit a new waiver
request unless the applicant wishes to use a different data lock point
or change the frequency of reporting.
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 request a waiver to change
the data lock point and this waiver request should include a
description of the measures taken to ensure that there are no resulting
gaps in reporting with the change.
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 applicant must request a waiver. This waiver request should
describe the measures taken to ensure that the periodicity requirements
under Sec. Sec. 314.80(c)(2)(i) and 600.80(c)(2)(i) are being met. If
an applicant requests to submit a PBRER less frequently than is
permitted under the applicant's PSUR waiver, 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 draft guidance also states that if an applicant is on
a quarterly reporting schedule but wishes to submit a PBRER every 6
months without submitting a quarterly PADER/PAER in the intervening
quarters, the applicant may request a waiver of the quarterly reporting
requirement.
FDA expects approximately 189 waiver requests to include the
additional information and notifications 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 and
notifications described previously would be on average approximately 1
hour for each waiver request.
If an applicant does not have a PSUR waiver in place for an
approved application, the applicant may submit a waiver request under
Sec. 314.90(a) or Sec. 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 April 8, 2013, draft guidance. Each PBRER waiver request should
include the following information:
(1) The product name(s) and application number(s);
(2) A brief description of the justification for the request;
(3) The U.S. approval date for the product(s) and current reporting
interval used;
(4) The reporting interval of the last PADER/PAER submitted for the
product(s);
(5) 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).
(6) The frequency for submitting the PBRER, as described in section
IV.C of the April 8, 2013, draft guidance.
(7) 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. Sec. 314.90(a)
or 600.90(a) permit applicants to request waivers of any postmarketing
safety reporting requirement, and the information collections
associated with such waiver requests generally are approved under OMB
control numbers 0910-0001and 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 postmarketing 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:
Table 1--Estimated Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 74154]]
Dated: December 3, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-29393 Filed 12-9-13; 8:45 am]
BILLING CODE 4160-01-P
