In December 2014, FDA released the finalized Guidance for Industry “Providing Regulatory Submissions in Electronic Format—Standardized Study Data.” This presentation reviews key points in the guidance and discusses the implications for Sponsors currently conducting studies as well as those who will be starting new studies soon.

1. Confused by FDA Guidance
on Standardized Study Data
for Electronic Submissions?

2. Ben Vaughn
• Principal Statistical Scientist
Rob Woolson
• Chief Strategist-Biostatistics &
Standards for Regulatory
Submissions

3. Context
FDA has been accepting electronic submissions (as
we currently think of them) since the 1999 eNDA
Guidance was issued
In 2003 the eCTD Guidance was issued, formalizing
the structure of electronic submissions and made a
requirement for electronic submissions in 2008
CDER began accepting SDTM in 2004, however FDA
had not previously made this a formal requirement

4. Context
Electronic Standardized Study Data Timeline
(Source: Fitzmartin, PhUSE 2014)

5. FDASIA 745A(a) Guidance
Binding Guidance Requiring Submissions in
Electronic Format
•“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.”

6. Which submissions must be
submitted electronically?
Certain INDs
NDAs
ANDAs
Certain BLAs
Also includes subsequent
submissions, including amendments.

7. FDA Implementation of New
Requirements
Draft
guidances
will be
posted for
review
Comment
period
Finalization
period
Final
guidance
announced
and posted
No earlier
than 24
months
after a final
guidance is
issued

8. Summary of FDASIA 745A(a)
Guidance
Umbrella document to describe the process
This is a BINDING GUIDANCE
Since this is a BINDING GUIDANCE, failure to follow the
technical conformance rules can result in a REFUSAL TO
FILE.
Assume that this Guidance, and subsequent technical
guidances, will apply to all submissions to CDER and CBER.

9. eStudy Data Guidance
Binding Guidance Requiring a Standardized Data Format
• “This guidance implements the electronic submission
requirements of section 745A(a) of the FD&C Act for study data
contained in 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) by specifying the
format for the electronic submission of such submissions.
Submissions that are not submitted electronically and
electronic submissions that are not in a format that FDA can
process, review, and archive will not be filed or received …”

10. Which submissions must follow a
standardized data format?
Certain INDs
NDAs
ANDAs
Certain BLAs
 Also includes subsequent submissions, including
amendments.
 Some exemptions: devices, some INDs.

11. What standardized formats
MUST be used?
Some
examples
•Exchange format: .pdf, .xpt,
.xml
•Clinical data: SDTM
•Analysis data: ADaM
•Terminology: CDISC controlled
terminology, MedDRA
The standards, formats, and terminologies
specified in the Data Standards Catalog
posted to the FDA’s web page.

12. And what if standardized
formats are not used?
“The FDA will not provide waivers to submit
data that do not conform to any FDA-supported
study data standard. However, sponsors or
applicants may apply for a waiver from the
requirement to use specific versions of
standards, formats, or terminologies.”

13. Timing of Specific Requirements
•Studies starting 24 months
after the ‘Transition Date’
– the March 15th after the
Federal Register notice
Guidance
(e.g., a new
standard)
•Studies starting 12 months
after the ‘Transition Date’
– the March 15th after the
Federal Register notice
Standards
Version
Update

14. Working with the FDA
Meetings with FDA
•Use established FDA-sponsor meetings (e.g., pre-
IND, EOP2, etc.) to discuss the study data
standardization plan
•Technical questions related to data standards can
be submitted at any time to the technical support
team identified by each Center; a Type C meeting
can be requested for substantive issues
Implementation Support

15. Summary of eStudy Data
Guidance
First Guidance document under the 745A(a) umbrella.
This is a BINDING GUIDANCE
Since this is a BINDING GUIDANCE, failure to follow the
technical conformance rules can result in a REFUSAL TO
FILE.
Assume that this Guidance, and subsequent technical
guidances, will apply to all submissions to CDER and CBER.

16. Study Data Technical
Conformance Guide
Technical Specifications Document
• Guidance supplements eStudy Data
Guidance
• Provides technical specifications briefly
described in the eStudy Data Guidance
• Is a single document containing earlier
recommendations contained in the
Common Data Issues Document and the
Study Data Specifications Document.

17. Study Data Tech Guide -
Contents

18. Study Data Tech Guide
Background
•Provides technical recommendations; non-
binding
•FDA acknowledges that there may be
variability in implementation
•Though, deviate at your own risk
•This is intended to be a living document where
the FDA updates technical recommendations,
preferences, and errors to avoid

19. Study Data Tech Guide
Study Data Standardization Plan (include
in the IND). Should include the following:
•List of planned studies
•Types of studies
•Study designs
•Planned data standards
•List of justifications for studies that do not
conform

20. Study Data Tech Guide
Study Data Reviewer Guide. Should
include the following:
•Study protocol, title, number, version
•Study design
•Standards, formats, terminologies
•Description of study datasets
•Data standards conformance validation
rules, versions, and issues

21. Study Data Tech
Study Data
Submission Format:
• CDISC: FDA’s strongest endorsement of
SDTM/ADaM

22. In Conclusion …
Read the Guidances
Start conversations with FDA at pre-IND stage
regarding data standards
Educate, educate, educate