
[Federal Register Volume 79, Number 243 (Thursday, December 18, 2014)]
[Notices]
[Pages 75568-75569]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-29608]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0097]


Providing Regulatory Submissions in Electronic Format--
Standardized Study Data; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Providing Regulatory 
Submissions in Electronic Format--Standardized Study Data.'' The 
guidance announced in this document is being issued in accordance with 
the Food and Drug Administration Safety and Innovation Act (FDASIA), 
which amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act) 
to require that certain submissions under the FD&C Act and Public 
Health Service Act (PHS Act) be submitted in electronic format, 
beginning no earlier than 24 months after issuance of final guidance on 
that topic. The guidance describes how FDA plans to implement the 
requirements for the electronic submission of standardized study data 
contained in certain submissions under new drug applications (NDAs), 
abbreviated new drug applications (ANDAs), biologics license 
applications (BLAs), and investigational new drug applications (INDs). 
This finalizes the revised draft guidance that was issued on February 
6, 2014.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of the documents 
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; or the Office 
of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, 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 documents.
    Submit electronic comments on the guidance to http://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: Ron Fitzmartin, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 1192, Silver Spring, MD 20993-0002, 
ronald.fitzmartin@fda.hhs.gov; or Stephen Ripley, Center for Biologics 
Evaluation and Research, Food and Drug Administration, Bldg. 71, rm. 
7301, Silver Spring, MD 20993, stephen.ripley@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    FDASIA (Pub. L. 112-144), signed by the President on July 9, 2012, 
amended the FD&C Act to add section 745A, entitled ``Electronic Format 
for Submissions.'' Section 745A(a)(1) of the FD&C Act requires that 
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 sections 351(a) or 
(k) of the PHS Act (42 U.S. C. 262(a) or (k)) be submitted to FDA in 
electronic format no earlier than 24 months after FDA issues final 
guidance on that topic.
    In accordance with section 745A(a)(1) of the FD&C Act, FDA is 
issuing this guidance, announcing its determination that the study data 
contained in the submission types identified in this guidance must be 
submitted electronically (except for submissions that are exempted), in 
a format that FDA can process, review, and archive. Currently, the 
Agency can process, review, and archive electronic submissions of study 
data that use the standards, formats, and terminologies specified in 
the Data Standards Catalog \1\ posted to the FDA's Study Data Standards 
Resources Web page.
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    \1\ Available at http://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm.
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    In the Federal Register of February 6, 2014 (79 FR 7201), FDA 
announced the availability of the revised draft guidance entitled 
``Providing Regulatory Submissions in Electronic Format--Standardized 
Study Data.'' The comment period on the revised draft guidance ended on 
May 6, 2014. We reviewed all comments received on the draft guidance 
and revised several sections of the guidance. The updates include:
    Section II.A: (1) Clarified which INDs and BLAs are addressed in 
this guidance. Specifically, a footnote was added to clarify the 
meaning of ``certain'' in the context of BLAs and INDs and states that 
the guidance is not applicable to INDs for devices that are regulated 
by CBER as biological products under section 351 of the PHS Act and to 
INDs that are noncommercial. Further, the guidance is not applicable to 
those devices that are regulated by CBER as biological products under 
section 351 of the PHS Act. Examples are provided in this regard. (2) 
Clarified that both clinical and nonclinical study data are within the 
scope of the guidance.
    Section II.C: (1) Clarified that the Agency may refuse to file an 
NDA or BLA or refuse to receive an ANDA containing study data that are 
not in conformance with the required standards. (2) Clarified that both 
the Clinical Data Interchange Standards Consortium (CDISC) Study Data 
Tabulation Model (SDTM) and Standard Exchange for Nonclinical Data 
(SEND) are examples of study data standards for tabulations data. (3) 
Clarified that some controlled terminologies are extensible and permit 
additions to existing code lists. It is the expectation that sponsors 
or applicants will use the controlled terminologies maintained by 
external organizations as the standard.
    Section II.D: Clarified the waiver process.
    Section II.E: (1) Clarified that FDA recognizes that version 
updates to standards may be released in the interval between the start 
of a study and the submission of study data to the Agency and the Data 
Standards Catalog may list more than one version of a supported 
standard. (2) Specified the definition of study start date for both 
clinical and nonclinical studies. (3) Revised terminology to more 
clearly state when a particular requirement becomes required.
    This guidance implements the electronic submission requirements of 
section 745A(a) of the FD&C Act by specifying the format for electronic 
submission of study data contained in NDA, ANDA, BLA, and IND 
submissions. With the publication of this Federal Register notice of 
availability, all studies with a start date \2\ 24 months or later 
after the

[[Page 75569]]

Federal Register notice must use the appropriate FDA-supported 
standards, formats, and terminologies specified in the Data Standards 
Catalog for NDA, ANDA, and certain BLA submissions. Study data 
contained in certain IND submissions must use the specified formats for 
electronic submission in studies with a start date 36 months or later 
after this Federal Register notice of availability.
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    \2\ For purposes of this guidance, the study start date for 
clinical studies is the earliest date of informed consent among any 
subject that enrolled in the study. For example, see Study Start 
Date (also known as the study initiation date) in the SDTM Trial 
Summary Domain (TSPARMCD = SSTDTC). For nonclinical studies, the 
study start date is the date on which the study protocol or plan is 
approved (signed) by the Study Director. For example, see Study 
Start Date in the SEND Trial Summary Domain (TSPARMCD = STSTDTC), 
http://www.cdisc.org.
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    In section 745A(a) of the FD&C Act, Congress granted explicit 
authorization to FDA to implement the statutory electronic submission 
requirements by specifying the format for such submissions in guidance. 
Because this guidance provides such requirements under section 745A(a) 
of the FD&C Act, indicated by the use of the words must or required, it 
is not subject to the usual restrictions in FDA's good guidance 
practice regulations, such as the requirement that guidances not 
establish legally enforceable responsibilities. See 21 CFR 10.115(d).

II. Paperwork Reduction Act of 1995

    The guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The guidance pertains to sponsors and applicants making 
regulatory submissions to FDA in electronic format for NDAs, ANDAs, 
BLAs, and INDs. The information collection discussed in the guidance is 
contained in our IND regulations (21 CFR part 312) and approved under 
OMB control number 0910-0014, our NDA regulations (including ANDAs) (21 
CFR part 314) and approved under OMB control number 0910-0001, and our 
BLA regulations (21 CFR part 601) and approved under OMB control number 
0910-0338.
    Sponsors and applicants have been voluntarily submitting 
standardized study data in electronic format. Under FDASIA, sponsors 
and applicants will be required to make all of these submissions 
electronically in compliance with the specified standards, formats, and 
terminologies. These requirements will be phased in over 2- and 3-year 
periods after the issuance of this guidance.
    For many years sponsors and applicants have been submitting 
electronically using the electronic common technical document format 
and have included electronic study data in both legacy and standardized 
formats. For some sponsors and applicants there may be new costs, 
including capital costs or operating and maintenance costs, which would 
result from the requirements under FDASIA and this guidance, because 
some sponsors and applicants would have to change from submissions that 
have included legacy (non-standard) study data to submissions in 
compliance with this guidance. FDA estimates that for some sponsors and 
applicants the costs may be as follows:

 Data management (hardware/software): $350,000-$1,000,000
 Initial data management operations: $500,000-$1,000,000
 Training: $100,000--$250,000

III. Comments

    Interested persons may submit either electronic comments to http://www.regulations.gov or written comments regarding this document 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 http://www.regulations.gov.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.regulations.gov.

    Dated: December 12, 2014.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2014-29608 Filed 12-17-14; 8:45 am]
BILLING CODE 4164-01-P


