1. Electronic Submissions
Shakul Hameed

2. What are Electronic Submissions?
A Regulatory application submitted via
network or web directory to regulatory
agencies..
Marketing Approval
 IND, NDA, BLA, Correspondences, Safety Reports
 MAA, CTA, 510ks, other marketing apps…
Special formats for creating documents
PDF, XML, SAS, MSWord, JPG

3. History of Electronic
Submissions
 1980s: Computer Assisted NDA (CANDA)
 1995: CDER’s Submission Management and Review
Tracking (SMART)
 1997: CFR, Part 11 and PDUFA
 1998 and 1999: Guidance Doc
 2002: ICH Guidance M2
 2006: Providing Electronic Submissions
 NDA, IND, ANDA, DMF, 510K and PMA, etc
 Amendment docs: Annual Reports, Labeling

4. Key Benefits
 Paperless, or near paperless submissions for faster
marketing approval
 Seamless, fast exchange of information within and
across agency centers and external to the agency.
 Elimination of duplication.
 Rigorous records management and document
control tracking, and archiving.
 Electronic data Interchange (EDI) capability for
data exchange.
 Standards-based infrastructure..
 Standards-based information repositories and data
dictionaries

5. e-Submission vs eCTD
 Important distinction: eSubmission ≠ eCTD, NeeS
 The eCTD and NeeS is a particular type of electronic
submission (NeeS applicable only for Europe)
 Moving now towards the implementation of the
eCTD as the specific format for electronic
submission
 Moving also towards the acceptance of electronic-
only submissions, with eCTD the preferred
standard. No paper requirement.

6. eCTD
 Electronic Common Technical Document
 Method to electronically transfer product
information and data collection of electronic
files organized according to guidelines defining
file format, folder/file naming conventions,
document specifications, etc…..
 Designed with considerations that facilitate
 Creation
 Review
 Life Cycle Management
 Archiving

7. Structure of eCTD
 Building blocks:
 PDF files for text*
 SAS transport files for data*
 Connected through XML backbone
 Looks like a web page
 Viewing
 Links and bookmarks
 Search keywords, metadata
 Managing lifecycle (Append, Replace, Delete)

8. eCTD File Structure

9. eCTD File Structure Cont….

10. Example of XML Backbone

11. XML Mapping to Folders

12.  Submission + knowledge management
 Technology driven
 Project management
 Business skills
Paper to Electronic (R) evolution

13. Paper/e-submission Comparison
Paper submissions Electronic
No Specialized Software Specialized E-publishing
software's
Overall and Module TOCs XML Back bone = TOC
Printed Documents and
various formats
Electronic document, PDF
Format
Tabs for Navigation Bookmarks and Hyperlinks
for Navigation
More Physical Storage Space Less Physical Storage Space
More time to pack and ship Less time to pack and ship
ESG available
Less efficient access and
review
More efficient access and
review
Difficult to review entire
submission lifecycle
Easy to review entire
submission lifecycle

14. Paper/Paper/e-submission cont….cont….

15. NeeS
 This is a European-only specification
 Initially developed as ‘interim’ as a lead in
to eCTD–But will probably have a long
duration of use
 Should be an eCTD without the backbone
but with PDF table(s) of content

16. NeeS/eCTD Comparison
e-CTD EU-NeeS
Format defined at ICH Harmonized European
Format
XML:
<<backbone>> (TOC) -
Lifecycle Management
No XML ( Backbone /
Envelope)
No life Cycle Management
PDF 1.4 Files (Including
Application form and SPC)
PDF 1.4, ICH
ICH file Naming Conventions
(Highly Recommended)
File Naming Conventions
Mandatory
Hyperlinks One General TOC
One Specific TOC per
Module (m1-toc.pdf….)
When Necessary
MD5 Checksums No checksums

17. eCTD/NeeS Comparison

18. eCTD/NeeS Comparison Cont….

19. Encouraging the use of eCTD
 Adapting to an international standard
 Facilitating the management of MA-
dossiers
 Facilitating archiving of applications
 Reduce the use of paper
 Streamline the assessment process
 Moving toward a more efficient system.

20. The Future of e-submissions
• The FDA is steadily moving toward a fully
electronic regulatory environment across
ALL Divisions
• As it works to achieve this goal, the FDA is
seeking to help to develop and adopt more
robust standards that promote increased
review quality and organizational efficiency

21. The Future of eCTD will be RPS
Regulated Product Submissions
All FDA Divisions to be on the same platform for
cost efficiencies ~2012
Based on XML similarities to eCTD
Standards predicted to converge with eCTD 4.0

22. RPS vs. eCTD
RPS eCTD
FDA harmonized Divisions Global Standard
Not EU, Global Rigid folder structure
Improved metadata and life cycle Difficult Lifecycle tracking
Better DM integration Limited concept of
Submissions/RU
Single XML file Multiple XML files
Undefined folder structure FDA Divisions not
satisfied/unified
Two way communication Metadata problems (can’t be
corrected, poor life cycle issues)
Hyperlink content to content Limited “relative” hyperlinks
Same tools as eCTD eCTD 4.0 may converge with RPS

23. eSubmission Advantages
• Relieves resource burdens related to paper
distribution & storage
• Makes review process faster, more efficient
• Ease of searching through data
• Documents easily accessible for years to come
• Facilitates life cycle management

24. eSubmission Challenges
 Still new and unfamiliar to many reviewers
 Full text search not fully implemented
 Diversity of strategies,
 e.g.Quality Overall Summary
 Amendments
 Supplements
 INDs [don’t include all data here, use
Module 3]
 Diversity of data presentation
 Diversity of “leaf” naming conventions

25. Life Before e-submissions

26. Conclusion
 Send submissions electronically
 Try to make submissions user-friendly
 More efficient review work benefits all of us