Submission of Content Necessary for Bioresearch Monitoring Inspection Planning for the Center of Drug Evaluation and Research; Availability, 7043-7046 [2018-03236]
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Federal Register / Vol. 83, No. 33 / Friday, February 16, 2018 / Notices
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 § 10.20 (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.fda.gov/
regulatoryinformation/dockets/
default.htm.
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:
Beverly Friedman, Office of Regulatory
Policy, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 51,
Rm. 6250, Silver Spring, MD 20993,
301–796–3600.
SUPPLEMENTARY INFORMATION:
daltland on DSKBBV9HB2PROD with NOTICES
I. Background
The Drug Price Competition and
Patent Term Restoration Act of 1984
(Pub. L. 98–417) and the Generic
Animal Drug and Patent Term
Restoration Act (Pub. L. 100–670)
generally provide that a patent may be
extended for a period of up to 5 years
so long as the patented item (human
drug product, animal drug product,
medical device, food additive, or color
additive) was subject to regulatory
review by FDA before the item was
marketed. Under these acts, a product’s
regulatory review period forms the basis
for determining the amount of extension
an applicant may receive.
A regulatory review period consists of
two periods of time: A testing phase and
an approval phase. For human drug
products, the testing phase begins when
the exemption to permit the clinical
investigations of the drug becomes
effective and runs until the approval
phase begins. The approval phase starts
with the initial submission of an
application to market the human drug
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product and continues until FDA grants
permission to market the drug product.
Although only a portion of a regulatory
review period may count toward the
actual amount of extension that the
Director of USPTO may award (for
example, half the testing phase must be
subtracted as well as any time that may
have occurred before the patent was
issued), FDA’s determination of the
length of a regulatory review period for
a human drug product will include all
of the testing phase and approval phase
as specified in 35 U.S.C. 156(g)(1)(B).
FDA has approved for marketing the
human drug product MOVANTIK
(naloxegol oxalate). MOVANTIK is
indicated for the treatment of opioidinduced constipation in adult patients
with chronic non-cancer pain.
Subsequent to this approval, the USPTO
received patent term restoration
applications for MOVANTIK (U.S.
Patent Nos. 7,662,365 and 7,786,133)
from Nektar Therapeutics, and the
USPTO requested FDA’s assistance in
determining the patents’ eligibility for
patent term restoration. In a letter dated
October 30, 2015, FDA advised the
USPTO that this human drug product
had undergone a regulatory review
period and that the approval of
MOVANTIK represented the first
permitted commercial marketing or use
of the product. Thereafter, the USPTO
requested that FDA determine the
product’s regulatory review period.
II. Determination of Regulatory Review
Period
FDA has determined that the
applicable regulatory review period for
MOVANTIK is 2,493 days. Of this time,
2,127 days occurred during the testing
phase of the regulatory review period,
while 366 days occurred during the
approval phase. These periods of time
were derived from the following dates:
1. The date an exemption under
section 505(i) of the Federal Food, Drug,
and Cosmetic Act (the FD&C Act) (21
U.S.C. 355(i)) became effective:
November 21, 2007. The applicant
claims October 22, 2007, as the date the
investigational new drug application
(IND) became effective. However, FDA
records indicate that the IND effective
date was November 21, 2007, which was
30 days after FDA receipt of the IND.
2. The date the application was
initially submitted with respect to the
human drug product under section
505(b) of the FD&C Act: September 16,
2013. FDA has verified the applicant’s
claim that the new drug application
(NDA) for MOVANTIK (NDA 204760)
was initially submitted on September
16, 2013.
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3. The date the application was
approved: September 16, 2014. FDA has
verified the applicant’s claim that NDA
204760 was approved on September 16,
2014.
This determination of the regulatory
review period establishes the maximum
potential length of a patent extension.
However, the USPTO applies several
statutory limitations in its calculations
of the actual period for patent extension.
In its applications for patent extension,
this applicant seeks 1,020 days or 272
days of patent term extension.
III. Petitions
Anyone with knowledge that any of
the dates as published are incorrect may
submit either electronic or written
comments and, under 21 CFR 60.24, ask
for a redetermination (see DATES).
Furthermore, as specified in § 60.30 (21
CFR 60.30), any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period. To
meet its burden, the petition must
comply with all the requirements of
§ 60.30, including but not limited to:
Must be timely (see DATES), must be
filed in accordance with § 10.20, must
contain sufficient facts to merit an FDA
investigation, and must certify that a
true and complete copy of the petition
has been served upon the patent
applicant. (See H. Rept. 857, part 1, 98th
Cong., 2d sess., pp. 41–42, 1984.)
Petitions should be in the format
specified in 21 CFR 10.30.
Submit petitions electronically to
https://www.regulations.gov at Docket
No. FDA–2013–S–0610. Submit written
petitions (two copies are required) to the
Dockets Management Staff (HFA–305),
Food and Drug Administration, 5630
Fishers Lane, Rm. 1061, Rockville, MD
20852.
Dated: February 13, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–03245 Filed 2–15–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–D–0481]
Submission of Content Necessary for
Bioresearch Monitoring Inspection
Planning for the Center of Drug
Evaluation and Research; Availability
AGENCY:
Food and Drug Administration,
HHS.
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ACTION:
Federal Register / Vol. 83, No. 33 / Friday, February 16, 2018 / Notices
Notice of availability.
The Food and Drug
Administration (FDA or the Agency) is
announcing the availability of a draft
guidance for industry entitled
‘‘Standardized Format for Electronic
Submission of NDA and BLA Content
for the Planning of Bioresearch
Monitoring (BIMO) Inspections for
CDER Submissions’’ along with the
Bioresearch Monitoring Technical
Conformance Guide Containing
Technical Specifications (BIMO
Technical Conformance Guide). The
draft guidance and BIMO Technical
Conformance Guide describe and
provide specifications for the electronic
submission of certain data and
information in standardized formats.
This information is used by the Center
for Drug Evaluation and Research
(CDER) in the planning of, and by FDA’s
Office of Regulatory Affairs (ORA) in the
conduct of, bioresearch monitoring
(BIMO) inspections. The draft guidance
addresses major (i.e., pivotal) studies
used to support safety and efficacy
claims in new drug applications (NDAs)
and biologics license applications
(BLAs) regulated by CDER, as well as
certain supplemental applications
containing new clinical study reports.
This draft guidance, when finalized, is
intended to assist applicants in the
submission of electronic data and
information in standardized formats,
and supersedes the previously issued
draft guidance entitled ‘‘Providing
Submissions in Electronic Format—
Summary Level Clinical Site Data for
CDER’s Inspection Planning’’ (December
2012) (Summary Level Clinical Site
Draft Guidance).
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 April 17, 2018.
ADDRESSES: You may submit comments
as follows:
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SUMMARY:
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
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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–
2018–D–0481 for ‘‘Standardized Format
for Electronic Submission of New Drug
Application and Certain Biologics
License Application Content for the
Planning of Bioresearch Monitoring
Inspections for Submissions to the
Center for Drug Evaluation and
Research; Draft Guidance for Industry;
Bioresearch Monitoring Technical
Conformance Guide Containing
Technical Specifications; Availability.’’
Received comments 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
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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
‘‘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/201523389.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.
Submit written requests for single
copies of this draft guidance to the
Division of Drug Information, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10001 New
Hampshire Ave., Hillandale Building,
4th Floor, 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.
FOR FURTHER INFORMATION CONTACT: Jean
Mulinde, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Silver Spring, MD 20993–0002,
301–796–0768.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of:
(1) A draft guidance for industry
entitled ‘‘Standardized Format for
Electronic Submission of NDA and BLA
Content for the Planning of Bioresearch
Monitoring Inspections (BIMO) for
CDER Submissions’’ and (2) the BIMO
Technical Conformance Guide. This
draft guidance and the BIMO Technical
Conformance Guide describe and
provide specifications for the electronic
submission of data and information in
standardized formats, for submitting
information used by CDER in the
planning of, and by ORA in the conduct
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Federal Register / Vol. 83, No. 33 / Friday, February 16, 2018 / Notices
of, BIMO inspections. The draft
guidance and the technical conformance
guide address major (i.e., pivotal)
studies used to support safety and
efficacy claims in NDAs, BLAs, and
NDA and BLA supplemental
applications containing new clinical
study reports that are regulated by
CDER.
To meet its review performance goals
in accordance with CDER good review
management principles and practices
for products covered by the Prescription
Drug User Fee Act, CDER generally
initiates inspection planning early in
the application review process (i.e.,
during the filing determination and
review planning phase). CDER’s
inspection planning includes the
selection of clinical investigator sites
and other regulated entities for on-site
inspections, and the preparation of
assignment memos and background
packages that CDER provides to FDA’s
ORA, which performs FDA’s BIMO
inspections. CDER uses the data and
information described in this guidance
to plan BIMO inspections, including: (1)
To facilitate the timely identification of
sites for inspection and (2) to ensure the
availability of information needed to
conduct BIMO inspections by ORA
investigators.
This draft guidance and the associated
technical conformance guide supersede
the previously issued Summary Level
Clinical Site Draft Guidance that
published in the Federal Register on
December 19, 2012 (77 FR 75174). FDA
carefully considered all of the
comments received to the docket for the
Summary Level Clinical Site Draft
Guidance in developing this guidance.
This draft guidance includes
clarifications, additional detail on some
topics, revised nomenclature for some
data variables, and descriptions of
additional data and information in
standardized formats that are submitted
in NDAs and BLAs to CDER, to facilitate
the planning of routine BIMO
inspections.
In section 745A(a) of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C.
379k–1(a)), Congress granted explicit
authorization to FDA to specify, in
guidance, the electronic format for
submissions under section 505(b), (i), or
(j) of the FD&C Act (21 U.S.C. 355(b), (i),
or (j)) and submissions under section
351(a) or (k) of the Public Health Service
Act (42 U.S.C. 262(a) or (k)).
Accordingly, to the extent that this
guidance, when finalized, provides such
requirements, as indicated by the use of
the words must or required, this
guidance will not be subject to the usual
restrictions in FDA’s good guidance
practice (GGP) regulations, such as the
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requirement that guidances not establish
legally enforceable responsibilities (see
21 CFR 10.115(d); see also the guidance
for industry ‘‘Providing Regulatory
Submissions in Electronic Format—
Submissions Under Section 745A(a) of
the Federal Food, Drug, and Cosmetic
Act,’’ available at https://www.fda.gov/
Drugs/GuidanceComplianceRegulatory
Information/Guidances/default.htm.
To comply with GGP regulations and
make sure that regulated entities and the
public understand that guidance
documents are nonbinding, FDA
guidances ordinarily contain standard
language explaining that guidance
documents should be viewed only as
recommendations unless specific
regulatory or statutory requirements are
cited. FDA is not including this
standard language in this draft guidance
document because it is not an accurate
description of this guidance. Insofar as
this guidance specifies the format for
electronic submissions pursuant to
section 745A(a) of the FD&C Act, when
finalized, it will have binding effect.
The draft guidance and the BIMO
Technical Conformance Guide, when
finalized, will represent the current
thinking of FDA on standardized format
for electronic submission of NDA and
BLA content for the planning of BIMO
inspections for CDER Submissions.
II. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act
of 1995 (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 that 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 for each proposed
collection of information before
submitting the collection to OMB for
approval. To comply with this
requirement, FDA is publishing this
notice of the proposed collection of
information set forth in this document.
With respect to the collection of
information associated with this draft
guidance and the associated technical
conformance guide, FDA invites
comments on the following topics: (1)
Whether the proposed information
collected is necessary for the proper
performance of FDA’s functions,
including whether the information will
have practical utility; (2) the accuracy of
FDA’s estimated burden of the proposed
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information collected, including the
validity of the methodology and
assumptions used; (3) ways to enhance
the quality, utility, and clarity of the
information collected; and (4) ways to
minimize the burden of information
collected on the respondents, including
through the use of automated collection
techniques, when appropriate, and other
forms of information technology.
The draft guidance and the
Bioresearch Monitoring Technical
Conformance Guide provide the
electronic format and specifications for
submission of data and information
used by CDER in the planning of, and
by ORA in the conduct of, BIMO
inspections. Data and information
described in the draft guidance
comprises information required in parts
312, 314, or 601 (21 CFR parts 312, 314,
or 601), including case histories
(§ 312.62(b)), information regarding
foreign clinical studies not conducted
under an investigational new drug
application (IND) (§ 312.120), and the
clinical data section (§ 314.50(d)(5)) and
case report forms and tabulations
(§ 314.50(f)), or in part 601 (§ 601.2
Applications for biologics licenses;
procedures for filing) in an NDA, BLA,
or supplement. The draft guidance and
the associated technical conformance
guide describe the electronic format of
clinical study-level information, subjectlevel data line listings by clinical site,
and the summary-level clinical site
dataset that are submitted from all major
(i.e., pivotal) studies used to support
safety and efficacy claims in NDAs,
BLAs, and NDA and BLA supplemental
applications containing new clinical
study reports. The variables described
in the format are elements currently
used in other submissions; some of the
variable names described in the
summary-level clinical site dataset are
new. The financial disclosure
information is currently reported in
Module 1 (region specific information)
of the electronic common technical
document, but is new as a variable in
the summary-level clinical site dataset.
In addition, identifying that a study has
been conducted under an IND is new as
a request in a dataset. Initial preparation
of some of the clinical study-level
information, the subject-level data line
listings by clinical site, and the
summary-level clinical site dataset and
the development of new standard
operating procedures (SOPs) would
require added time. Once SOPs have
been established, generation of the
clinical study-level information, subjectlevel data line listings by clinical site,
and the summary-level clinical site
dataset should not involve significant
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Federal Register / Vol. 83, No. 33 / Friday, February 16, 2018 / Notices
additional work. The applicant would
likely perform more quality assurance,
which may add time to preparation and
review of the submission.
Based on CDER’s data on the number
of NDAs, BLAs, and NDA and BLA
supplemental applications containing
new clinical study reports that would be
covered by the draft guidance, we
estimate that each year approximately
75 applicants will submit for 125
original NDA or BLA applications and
152 supplemental applications
containing new clinical study reports.
We estimate that the submission of the
clinical study-level information, subjectlevel data line listings by clinical site,
and the summary-level clinical site
dataset for each application would take
approximately 40 hours to prepare.
Initial preparation of the clinical studylevel information, subject-level data line
listings by clinical site, and the
summary-level clinical site dataset
could involve the development of new
SOPs for some applicants. We estimate
that 75 applicants would take
approximately 20 hours to develop and
subsequently 2 hours annually to
maintain and update the SOP(s). The
clinical study-level information, subjectlevel data line listings by clinical site,
and the summary-level clinical site
dataset submitted with each application
would likely involve additional quality
assurance procedures, which would add
approximately 2 hours for each
submission.
This draft guidance also refers to
previously approved collections of
information found in FDA regulations.
The collections of information in part
312 have been approved under OMB
control number 0910–0014; the
collections of information in part 314
have been approved under OMB control
number 0910–0001; the collections of
information in part 601 have been
approved under OMB control number
0910–0338.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED REPORTING BURDEN 1
Number of
responses per
respondent
(i.e., applications)
Number of
respondents
(i.e., applicants)
Activity
Total
responses
Hours per
response
Total hours
Submissions (clinical study-level information,
subject-level data line listings by clinical
site, and the summary-level clinical site
dataset) .........................................................
Quality Assurance ............................................
75
75
3.7
3.7
277
277
40
2
11,080
554
Total ..........................................................
................................
....................................
........................
........................
11,634
1 There
are no capital costs or operating and maintenance costs associated with this information collection.
TABLE 2—ESTIMATED RECORDKEEPING BURDEN 1
Number of
recordkeepers
Activity
Number of
records per
recordkeeper
Total
records
Hours per
recordkeeper
Total hours
Develop Initial SOP(s) .........................................................
Maintain and Update SOP(s) ...............................................
75
75
1
1
75
75
20
2
1,500
150
Total ..............................................................................
........................
........................
........................
........................
1,650
1 There
are no capital costs or operating and maintenance costs associated with this information collection.
II. Electronic Access
Persons with access to the internet
may obtain the draft guidance at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm or https://
www.regulations.gov.
Dated: February 9, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–03236 Filed 2–15–18; 8:45 am]
Food and Drug Administration
[Docket No. FDA–2017–P–4852]
Determination That LOTENSIN HCT
(Benazepril Hydrochloride;
Hydrochlorothiazide) Oral Tablets, 5
Milligrams and 6.25 Milligrams, Were
Not Withdrawn From Sale for Reasons
of Safety or Effectiveness
AGENCY:
BILLING CODE 4164–01–P
daltland on DSKBBV9HB2PROD with NOTICES
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or Agency) has
determined that LOTENSIN HCT
(benazepril hydrochloride;
hydrochlorothiazide) oral tablets, 5
milligrams (mg) and 6.25 mg, were not
SUMMARY:
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withdrawn from sale for reasons of
safety or effectiveness. This
determination will allow FDA to
approve abbreviated new drug
applications (ANDAs) for benazepril
hydrochloride; hydrochlorothiazide oral
tablets, 5 mg and 6.25 mg, if all other
legal and regulatory requirements are
met.
FOR FURTHER INFORMATION CONTACT:
Stacy Kane, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 6236, Silver Spring,
MD 20993–0002, 301–796–8363,
Stacy.Kane@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In 1984,
Congress enacted the Drug Price
Competition and Patent Term
Restoration Act of 1984 (Pub. L. 98–417)
(the 1984 amendments), which
authorized the approval of duplicate
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]]>Agencies
[Federal Register Volume 83, Number 33 (Friday, February 16, 2018)]
[Notices]
[Pages 7043-7046]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-03236]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-D-0481]
Submission of Content Necessary for Bioresearch Monitoring
Inspection Planning for the Center of Drug Evaluation and Research;
Availability
AGENCY: Food and Drug Administration, HHS.
[[Page 7044]]
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the availability of a draft guidance for industry entitled
``Standardized Format for Electronic Submission of NDA and BLA Content
for the Planning of Bioresearch Monitoring (BIMO) Inspections for CDER
Submissions'' along with the Bioresearch Monitoring Technical
Conformance Guide Containing Technical Specifications (BIMO Technical
Conformance Guide). The draft guidance and BIMO Technical Conformance
Guide describe and provide specifications for the electronic submission
of certain data and information in standardized formats. This
information is used by the Center for Drug Evaluation and Research
(CDER) in the planning of, and by FDA's Office of Regulatory Affairs
(ORA) in the conduct of, bioresearch monitoring (BIMO) inspections. The
draft guidance addresses major (i.e., pivotal) studies used to support
safety and efficacy claims in new drug applications (NDAs) and
biologics license applications (BLAs) regulated by CDER, as well as
certain supplemental applications containing new clinical study
reports. This draft guidance, when finalized, is intended to assist
applicants in the submission of electronic data and information in
standardized formats, and supersedes the previously issued draft
guidance entitled ``Providing Submissions in Electronic Format--Summary
Level Clinical Site Data for CDER's Inspection Planning'' (December
2012) (Summary Level Clinical Site Draft Guidance).
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 April 17, 2018.
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 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-2018-D-0481 for ``Standardized Format for Electronic Submission of
New Drug Application and Certain Biologics License Application Content
for the Planning of Bioresearch Monitoring Inspections for Submissions
to the Center for Drug Evaluation and Research; Draft Guidance for
Industry; Bioresearch Monitoring Technical Conformance Guide Containing
Technical Specifications; Availability.'' Received comments 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 ``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.
Submit written requests for single copies of this draft guidance to
the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10001 New Hampshire Ave.,
Hillandale Building, 4th Floor, 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.
FOR FURTHER INFORMATION CONTACT: Jean Mulinde, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-0768.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of: (1) A draft guidance for
industry entitled ``Standardized Format for Electronic Submission of
NDA and BLA Content for the Planning of Bioresearch Monitoring
Inspections (BIMO) for CDER Submissions'' and (2) the BIMO Technical
Conformance Guide. This draft guidance and the BIMO Technical
Conformance Guide describe and provide specifications for the
electronic submission of data and information in standardized formats,
for submitting information used by CDER in the planning of, and by ORA
in the conduct
[[Page 7045]]
of, BIMO inspections. The draft guidance and the technical conformance
guide address major (i.e., pivotal) studies used to support safety and
efficacy claims in NDAs, BLAs, and NDA and BLA supplemental
applications containing new clinical study reports that are regulated
by CDER.
To meet its review performance goals in accordance with CDER good
review management principles and practices for products covered by the
Prescription Drug User Fee Act, CDER generally initiates inspection
planning early in the application review process (i.e., during the
filing determination and review planning phase). CDER's inspection
planning includes the selection of clinical investigator sites and
other regulated entities for on-site inspections, and the preparation
of assignment memos and background packages that CDER provides to FDA's
ORA, which performs FDA's BIMO inspections. CDER uses the data and
information described in this guidance to plan BIMO inspections,
including: (1) To facilitate the timely identification of sites for
inspection and (2) to ensure the availability of information needed to
conduct BIMO inspections by ORA investigators.
This draft guidance and the associated technical conformance guide
supersede the previously issued Summary Level Clinical Site Draft
Guidance that published in the Federal Register on December 19, 2012
(77 FR 75174). FDA carefully considered all of the comments received to
the docket for the Summary Level Clinical Site Draft Guidance in
developing this guidance. This draft guidance includes clarifications,
additional detail on some topics, revised nomenclature for some data
variables, and descriptions of additional data and information in
standardized formats that are submitted in NDAs and BLAs to CDER, to
facilitate the planning of routine BIMO inspections.
In section 745A(a) of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 379k-1(a)), Congress granted explicit authorization to FDA to
specify, in guidance, the electronic format for submissions under
section 505(b), (i), or (j) of the FD&C Act (21 U.S.C. 355(b), (i), or
(j)) and submissions under section 351(a) or (k) of the Public Health
Service Act (42 U.S.C. 262(a) or (k)). Accordingly, to the extent that
this guidance, when finalized, provides such requirements, as indicated
by the use of the words must or required, this guidance will not be
subject to the usual restrictions in FDA's good guidance practice (GGP)
regulations, such as the requirement that guidances not establish
legally enforceable responsibilities (see 21 CFR 10.115(d); see also
the guidance for industry ``Providing Regulatory Submissions in
Electronic Format--Submissions Under Section 745A(a) of the Federal
Food, Drug, and Cosmetic Act,'' available at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
To comply with GGP regulations and make sure that regulated
entities and the public understand that guidance documents are
nonbinding, FDA guidances ordinarily contain standard language
explaining that guidance documents should be viewed only as
recommendations unless specific regulatory or statutory requirements
are cited. FDA is not including this standard language in this draft
guidance document because it is not an accurate description of this
guidance. Insofar as this guidance specifies the format for electronic
submissions pursuant to section 745A(a) of the FD&C Act, when
finalized, it will have binding effect.
The draft guidance and the BIMO Technical Conformance Guide, when
finalized, will represent the current thinking of FDA on standardized
format for electronic submission of NDA and BLA content for the
planning of BIMO inspections for CDER Submissions.
II. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act of 1995 (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 that
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 for each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing this notice of the
proposed collection of information set forth in this document.
With respect to the collection of information associated with this
draft guidance and the associated technical conformance guide, FDA
invites comments on the following topics: (1) Whether the proposed
information collected is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimated burden of the proposed
information collected, including the validity of the methodology and
assumptions used; (3) ways to enhance the quality, utility, and clarity
of the information collected; and (4) ways to minimize the burden of
information collected on the respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
The draft guidance and the Bioresearch Monitoring Technical
Conformance Guide provide the electronic format and specifications for
submission of data and information used by CDER in the planning of, and
by ORA in the conduct of, BIMO inspections. Data and information
described in the draft guidance comprises information required in parts
312, 314, or 601 (21 CFR parts 312, 314, or 601), including case
histories (Sec. 312.62(b)), information regarding foreign clinical
studies not conducted under an investigational new drug application
(IND) (Sec. 312.120), and the clinical data section (Sec.
314.50(d)(5)) and case report forms and tabulations (Sec. 314.50(f)),
or in part 601 (Sec. 601.2 Applications for biologics licenses;
procedures for filing) in an NDA, BLA, or supplement. The draft
guidance and the associated technical conformance guide describe the
electronic format of clinical study-level information, subject-level
data line listings by clinical site, and the summary-level clinical
site dataset that are submitted from all major (i.e., pivotal) studies
used to support safety and efficacy claims in NDAs, BLAs, and NDA and
BLA supplemental applications containing new clinical study reports.
The variables described in the format are elements currently used in
other submissions; some of the variable names described in the summary-
level clinical site dataset are new. The financial disclosure
information is currently reported in Module 1 (region specific
information) of the electronic common technical document, but is new as
a variable in the summary-level clinical site dataset. In addition,
identifying that a study has been conducted under an IND is new as a
request in a dataset. Initial preparation of some of the clinical
study-level information, the subject-level data line listings by
clinical site, and the summary-level clinical site dataset and the
development of new standard operating procedures (SOPs) would require
added time. Once SOPs have been established, generation of the clinical
study-level information, subject-level data line listings by clinical
site, and the summary-level clinical site dataset should not involve
significant
[[Page 7046]]
additional work. The applicant would likely perform more quality
assurance, which may add time to preparation and review of the
submission.
Based on CDER's data on the number of NDAs, BLAs, and NDA and BLA
supplemental applications containing new clinical study reports that
would be covered by the draft guidance, we estimate that each year
approximately 75 applicants will submit for 125 original NDA or BLA
applications and 152 supplemental applications containing new clinical
study reports. We estimate that the submission of the clinical study-
level information, subject-level data line listings by clinical site,
and the summary-level clinical site dataset for each application would
take approximately 40 hours to prepare. Initial preparation of the
clinical study-level information, subject-level data line listings by
clinical site, and the summary-level clinical site dataset could
involve the development of new SOPs for some applicants. We estimate
that 75 applicants would take approximately 20 hours to develop and
subsequently 2 hours annually to maintain and update the SOP(s). The
clinical study-level information, subject-level data line listings by
clinical site, and the summary-level clinical site dataset submitted
with each application would likely involve additional quality assurance
procedures, which would add approximately 2 hours for each submission.
This draft guidance also refers to previously approved collections
of information found in FDA regulations. The collections of information
in part 312 have been approved under OMB control number 0910-0014; the
collections of information in part 314 have been approved under OMB
control number 0910-0001; the collections of information in part 601
have been approved under OMB control number 0910-0338.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Number of responses
Activity respondents (i.e., per respondent Total Hours per Total hours
applicants) (i.e., applications) responses response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Submissions (clinical study-level information, subject-level 75 3.7 277 40 11,080
data line listings by clinical site, and the summary-level
clinical site dataset).......................................
Quality Assurance............................................. 75 3.7 277 2 554
-----------------------------------------------------------------------------------------
Total..................................................... .................. .................... .............. .............. 11,634
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
Table 2--Estimated Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
Activity Number of records per Total records Hours per Total hours
recordkeepers recordkeeper recordkeeper
----------------------------------------------------------------------------------------------------------------
Develop Initial SOP(s).......... 75 1 75 20 1,500
Maintain and Update SOP(s)...... 75 1 75 2 150
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 1,650
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
II. Electronic Access
Persons with access to the internet may obtain the draft guidance
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or
https://www.regulations.gov.
Dated: February 9, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-03236 Filed 2-15-18; 8:45 am]
BILLING CODE 4164-01-P
