[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]


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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.

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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announcing the availability of a draft guidance for industry entitled 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 The draft guidance and BIMO Technical Conformance 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draft guidance addresses major (i.e., pivotal) studies used to support 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 This draft guidance, when finalized, is intended to assist 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standardized formats, and supersedes the previously issued draft 
guidance entitled ``Providing Submissions in Electronic Format--Summary 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2012) (Summary Level Clinical Site Draft Guidance).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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by April 17, 2018.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\
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                                                                     Number of       Number of responses
                           Activity                             respondents (i.e.,     per respondent          Total         Hours per      Total hours
                                                                    applicants)     (i.e., applications)     responses       response
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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
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    Total.....................................................  ..................  ....................  ..............  ..............          11,634
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.


                                   Table 2--Estimated Recordkeeping Burden \1\
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                                                     Number of
            Activity                 Number of      records per    Total records     Hours per      Total hours
                                   recordkeepers   recordkeeper                    recordkeeper
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Develop Initial SOP(s)..........              75               1              75              20           1,500
Maintain and Update SOP(s)......              75               1              75               2             150
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    Total.......................  ..............  ..............  ..............  ..............           1,650
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\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