Providing Regulatory Submissions in 
Electronic Format  Submissions Under 
Section 745A(a) of the Federal Food, 
Drug, and Cosmetic Act 
 
 
 
 
 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
 
 
December 2014 
Electronic Submissions   
Providing Regulatory Submissions in 
Electronic Format  Submissions Under 
Section 745A(a) of the Federal Food, 
Drug, and Cosmetic Act 
 
 
 
 
 
 
Guidance for Industry 
 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993 
Phone: 800-835-4709 or 240-402-7800 
Email: ocod@fda.hhs.gov 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm    
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
December 2014 
Electronic Submissions 
    
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 4 
II.  BACKGROUND ............................................................................................................... 5 
III.  SUBMISSIONS UNDER SECTION 745A(a) OF THE FD&C ACT .......................... 6 
A.   Which submissions must be submitted electronically? .............................................................. 6 
B.  Which submissions are exempted from the electronic submission requirements? .................. 7 
C.   Will FDA issue waivers of the electronic submission requirements? ........................................ 7 
D.  How will FDA implement specific electronic submission requirements? ................................. 7 
E.  When will electronic submissions be required? .......................................................................... 8 
F.  When will revisions or updates to existing formats take effect? ................................................ 8 
    
 
Providing Regulatory Submissions in Electronic Format  
Submissions Under Section 745A(a) of the 
Federal Food, Drug, and Cosmetic Act  
1
Guidance for Industry  
 
 
I.  INTRODUCTION  
 
Section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), added by section 
1136 of the Food and Drug Administration Safety and Innovation Act (FDASIA) (Public 
Law 112-144), requires that submissions under section 505(b), (i), or (j) of the FD&C Act2 
and submissions under section 351(a) or (k) of the Public Health Service Act (PHS Act)3 be 
submitted in electronic format specified by the Food and Drug Administration (FDA or the 
Agency) beginning no earlier than 24 months after FDA issues a final guidance specifying an 
electronic submission format. 
 
The Agency has concluded that it is not feasible to describe and implement the electronic 
format(s) that would apply to all the submissions covered by section 745A(a) in one guidance 
document.  Accordingly, this guidance describes how FDA interprets and plans to implement 
the requirements of section 745A(a), while individual guidances (e.g., Providing Regulatory 
Submissions in Electronic Format --  Standardized Study Data4 and Providing Regulatory 
and Submissions in Electronic Format --  Human Pharmaceutical Product Applications and 
Related Submissions Using the eCTD Specifications5) will be developed to specify the 
formats for specific submissions and corresponding timetables for implementation.  
Specifically, this guidance discusses (1) the submission types that must be submitted 
electronically, (2) exemptions from and criteria for waivers of the electronic submission 
requirements, and (3) the timetable and process for implementing the requirements. 
 
Under the process described in this guidance, FDA will periodically issue guidances 
specifying the electronic format for types of submissions to new drug applications (NDAs), 
abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and 
investigational new drug applications (INDs) to the Center for Drug Evaluation and Research 
(CDER) or the Center for Biologics Evaluation and Research (CBER).  FDA believes that 
issuing this electronic submission guidance will harmonize and streamline the process for 
implementing the various required formats for electronic submissions under section 745A(a) 
of the FD&C Act.  The process described in this guidance is also intended to provide a 
meaningful opportunity for the public to comment on guidances that the Agency intends to 
issue pursuant to section 745A(a) of the FD&C Act. 
                                                 
1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for 
Biologics Evaluation and Research (CBER) at the Food and Drug Administration. 
2 21 U.S.C. 355(b), (i), or (j). 
3 42 U.S.C. 262 (a) or (k). 
4 See http://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm. 
5 See http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM333969.pdf. 
 
  4    
 
 
FDA guidances ordinarily contain standard language explaining that guidances should be 
viewed only as recommendations unless specific regulatory or statutory requirements are 
cited.  FDA is not including this standard language in this guidance because this guidance 
contains only binding provisions. 
 
II.  BACKGROUND 
 
FDASIA was enacted on July 9, 2012.  Section 1136 of FDASIA amended the FD&C Act by 
adding section 745A, which addresses electronic submissions.  Drug and biological product 
submissions are addressed in section 745A(a), while section 745A(b) applies to medical 
device submissions.6 
 
Section 745A(a)(1) of the FD&C Act describes the general scope of section 745A(a) and 
provides that submissions under NDAs, ANDAs, BLAs, and INDs must be in electronic 
format specified in FDA guidance: 
 
Beginning no earlier than 24 months after the issuance of a final guidance 
issued after public notice and opportunity for comment, submissions under 
subsection (b), (i), or (j) of section 505 of this Act or subsection (a) or (k) of 
section 351 of the Public Health Service Act shall be submitted in such 
electronic format as specified by the Secretary in such guidance. 
 
Section 745A(a)(2) states that the guidance issued by FDA may provide a timetable for 
future standards and criteria for waivers and exemptions: 
 
In the guidance under paragraph (1), the Secretary may (A) provide a 
timetable for establishment by the Secretary of further standards for electronic 
submission as required by such paragraph; and (B) set forth criteria for 
waivers of and exemptions from the requirements of this subsection. 
 
Section 745A(a)(3) provides that the requirements described in section 745A(a) do not apply 
to submissions under section 561 of the FD&C Act.7 
 
In Section 745A(a) of the FD&C Act, Congress granted explicit statutory authorization to 
FDA to specify in guidance the format for the electronic submissions required under this 
section.  Accordingly, to the extent that this document relates to such requirements under 
                                                 
6 The electronic submission requirements of section 745A(b) fall outside the scope of this guidance and are not 
discussed in this guidance.  We note, however, that FDA issued the final guidance entitled eCopy Program for 
Medical Device Submissions that implements the electronic copy provisions of section 745A(b) for medical 
device submissions to FDA.  We update guidances periodically.  For the most recent version of a guidance, see 
the FDA Drugs Guidance Web page at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm and its   
Biologics Web page at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm. 
7 Section 561 of the FD&C Act (21 U.S.C. 360bbb) relates to expanded access to  investigational products for 
the diagnosis, monitoring, or treatment of serious or immediately life-threatening diseases or conditions. 
  5    
 
section 745A(a), indicated by the use of the words must or required, this document is not 
subject to the usual restrictions in FDAs good guidance practice (GGP) regulations, such as 
the requirement that guidances not establish legally enforceable responsibilities.  See 21 CFR 
10.115(d). 
 
III.  SUBMISSIONS UNDER SECTION 745A(a) OF THE FD&C ACT 
 
As discussed in section II of this guidance, the requirements of section 745A(a) of the FD&C 
Act apply to all submissions to NDAs, ANDAs, BLAs, and INDs.  Below we discuss our 
interpretation of section 745A(a), specifically its scope, waivers of and exemptions from the 
electronic submission requirements, and the timetable and process for implementing the 
requirements under section 745A(a).   
 
A.   Which submissions must be submitted electronically? 
 
Section 745A(a) of the FD&C Act applies to submissions under section 505(b), (i), or (j) of 
the FD&C Act and under section 351(a) or (k) of the PHS Act.  These include the following 
submission types: 
  Certain investigational new drug applications (INDs)8  
  New drug applications (NDAs) 
  Abbreviated new drug applications (ANDAs) 
  Certain biologics license applications (BLAs)9  
 
Section 745A(a) also applies to all subsequent submissions, including amendments, 
supplements, and reports, to the submission types identified above.  Twenty-four months or 
more after FDA issues a final guidance covering any of these submission types, applicants or 
sponsors must electronically submit any amendments, supplements, and reports to those 
submission types,  even if the original submission was submitted to FDA prior to 
implementation of the electronic submission requirements.   
 
A submission that is not in the electronic format(s) described in the relevant guidance 
document will not be filed or received, unless it has been exempted from the electronic 
submission requirements or the electronic submission requirements have been waived with 
respect to that submission. 
 
                                                 
8 This guidance is not applicable to those devices that are regulated by CBER as biological products under 
section 351 of the PHS Act and that also require submission of an IND prior to submission of a BLA.  Such 
devices are generally those intended for use in screening donated blood for transfusion-transmissible diseases.  
These submissions are subject to the requirements under section 745A(b).  See the final guidance entitled eCopy 
Program for Medical Device Submissions, note 6. 
9 This guidance is not applicable to those devices that are regulated by CBER as biological products under 
section 351 of the PHS Act, including those that do not require submission of an IND prior to the submission of 
the BLA.  These submissions are subject to the requirements under section 745A(b).  Such devices generally 
include those reagents used in determining donor/recipient compatibility in transfusion medicine.  See the final 
guidance entitled eCopy Program for Medical Device Submissions, note 6. 
  6    
 
Under section 745A(a)(3) of the FD&C Act, the electronic submission requirements do not 
apply to submissions described in section 561 of the FD&C Act.  FDA will continue to 
accept submissions under section 561 in alternative formats.    
 
B.  Which submissions are exempted from the electronic submission 
requirements? 
 
Section 745A(a)(2)(B) authorizes FDA to establish exemptions from the electronic 
submission requirements.  As a general matter, the following submission types will be 
exempt from the electronic submission requirements under section 745A(a): 
 
1.  Noncommercial INDs, such as those that are described in Section 505(i)(1) of the 
FD&C Act.10  
 
Additional exemptions, if applicable, will be discussed in the individual guidances for 
specific submissions. 
 
C.   Will FDA issue waivers of the electronic submission requirements? 
 
The statute allows FDA to set forth criteria for waivers of the electronic submission 
requirements.  The criteria for any waivers, if available, will be discussed in the individual 
guidances for specific submissions. 
 
D.  How will FDA implement specific electronic submission requirements? 
 
FDA intends to use the following process to specify the electronic formats for submissions 
under section 745A(a): 
 
1.  Individual draft guidances will be developed to specify the electronic formats, subject 
matter, and scope of applicability for  submissions under section 745A(a).  The draft 
guidances will be posted on FDAs Drugs Guidance Web page and its Biologics 
Guidance Web page11 and will be announced in the list of new, revised, and 
withdrawn guidances.   
 
2.  The Agency will publish a notice in the Federal Register announcing the availability 
on the FDA Web site of a new or revised electronic submission guidance.  The notice 
will identify a comment period for the draft guidance. 
 
                                                 
10 For purposes of this guidance, the term noncommercial products refers to products that are not intended to 
be distributed commercially and includes investigator-sponsored INDs and expanded access INDs (e.g., 
emergency use INDs and treatment INDs). 
11 FDAs Drugs Guidance Web page is available at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, and its 
Biologics Guidance Web page is available at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm.  See 
Providing Regulatory Submissions in Electronic Format  Standardized Study Data as an example of an 
individual guidance under 745A(a). 
  7    
 
3.  Once the Agency has completed its review of the draft guidance, including comments 
submitted (if any), the Agency will publish a notice in the Federal Register 
announcing the availability on the FDA Web site of the final electronic submission 
guidance.  The notice will provide a date on which the new electronic submission 
formats specified in the guidance will be required for the submission types identified 
in the guidance document.  FDA will post the final guidance on its Drugs Guidance 
Web page and its Biologics Guidance Web page and will announce the guidance in 
the list of new, revised, and withdrawn guidances. 
 
4.  Subsequent revisions or updates to specified formats will be announced on the FDA 
Web site and published in the Federal Register.  The notice will provide a date on 
which the revised or updated electronic submission formats specified in the guidance 
will be required. 
 
E.  When will electronic submissions be required? 
 
Under section 745A(a)(1) of the FD&C Act, electronic submissions are required no earlier 
than 24 months after a final guidance is issued.  Therefore, no earlier than 24 months after 
the final version of an individual guidance specifying a new format for submissions under 
745A(a) is published on FDAs Web site, the Agency will begin requiring that the 
submissions to NDAs, ANDAs, BLAs, or INDs identified in that guidance be submitted in 
the specified electronic format.  The required format(s) for the specific submissions and 
corresponding timetable(s) for implementation will be specified in the individual guidances.  
Once an individual guidance is finalized and the timetable for implementation described in 
that guidance has passed, the guidance will be considered to have binding effect and the 
electronic format(s) specified in that guidance must be used for submissions to NDAs, 
ANDAs, BLAs, or INDs.   
 
F.  When will revisions and updates to existing formats take effect? 
 
FDA does not interpret section 745A(a) to impose a 24-month period before revisions and 
updates to an existing required electronic format can be implemented.  Therefore, subsequent 
revisions and updates to existing required format(s) may be implemented on a shorter 
timetable (e.g., 12 or 18 months after publication of the Federal Register notice announcing 
the availability of the revised format) depending, among other things, on whether the revision 
or update represents a significant change to the existing format.  For purposes of guidances 
issued pursuant to section 745A(a), FDA considers version updates and maintenance 
enhancements to be revisions to a specified format.  Under most circumstances, FDA 
considers a version update to be a number increment (e.g., version 3.0 to 4.0) or a decimal 
increment (e.g., version 3.1 to 3.2) to an existing format.  On the other hand, minor changes 
to a required format, such as corrections of typographical errors, may be implemented 
immediately or shortly after announcement of availability of the corrected format. 
 
The examples below illustrate how the Agency intends to interpret section 745A(a) with 
respect to the timing of the implementation of new formats, as well as revisions or updates to 
existing formats.  
  8    
 
 
Example 1:  New Format (with 24-Month Implementation Period) 
 
FDA issues a draft guidance specifying new format(s) for electronic submission of data 
contained in NDAs, ANDAs, BLAs, and INDs and publishes a Federal Register notice 
announcing availability of the draft guidance.  Following the comment period, FDA finalizes 
the guidance and publishes another Federal Register notice announcing availability of the 
final guidance.  The final guidance also provides that the specified format(s) will be required 
24 months after the date of its publication.  After the 24-month implementation period has 
passed, the guidance will have binding effect and the electronic formats specified in the 
guidance must be used for the submission types identified in the guidance document. 
 
Example 2:  New Format (with Longer Implementation Period) 
 
FDA issues a draft guidance specifying new format(s) for electronic submission of data 
contained in NDAs, ANDAs,  BLAs, and  INDs and publishes a Federal Register notice 
announcing availability of the draft guidance.  Following the comment period, FDA finalizes 
the guidance and publishes another Federal Register notice announcing availability of the 
final guidance.  The final guidance also provides that the specified format(s) will be required 
36 months after the date of its publication.  After the 36-month implementation period has 
passed, the guidance will have binding effect and the electronic formats specified in the 
guidance must be used for the submission types identified in the guidance document. 
 
  Example 3:  Update to Required Format 
 
FDA has finalized a guidance specifying new format(s) for electronic submission of data 
contained in NDAs, ANDAs, BLAs, and INDs, and the implementation timetable specified 
in that guidance has passed.  The guidance has binding effect, and the electronic formats 
specified in that guidance must be used for the submission types identified in the guidance 
document.  At a later date, FDA revises the guidance to reflect a version update to one or 
more of the electronic formats specified in the final guidance.  FDA also publishes a Federal 
Register notice announcing the availability of the revised guidance and a timetable for when 
submissions will be required to be made in the updated format.  This timetable may be for a 
period of time less than 24 months.   
 
Example 4:  Correction to Required Format 
 
FDA has finalized an individual guidance specifying new format(s) for electronic submission 
of data contained in NDAs, ANDAs, BLAs, and INDs, and the implementation timetable 
specified in the guidance has passed.  The guidance has binding effect, and the electronic 
formats specified in the guidance must be used for the submission types identified in the 
guidance document.  At a later date, FDA revises the guidance to make a correction to one or 
more of the formats specified in the final guidance.  FDA also publishes a Federal Register 
notice to announce the availability of the revised guidance as well as a timetable for when 
submissions will be required to be made in the corrected format.  This timetable may be for a 
period of time less than 24 months. 
  9