1. SAPRAA 5 Sept 2008 eCTD An overview of the full day presentation by Dr Olaf Schoepke at the SAAPI conference in July 2008

2. SAPRAA 5 Sept 2008 Overview History Why go electronic? Types of electronic submissions What eCTD consists of Preparing eCTD Eye openers and bombshells Conclusion

3. SAPRAA 5 Sept 2008 eSubmissions history Began in late 80’s but insufficient IT capabilities 1995 FDA used PDF files with hyperlinks 1997 CTD topic of ICH4 2001 first eCTD guideline 2003 CTD mandatory in EU and first eCTDs submitted 2006 lifecycle management a challenge

4. SAPRAA 5 Sept 2008 The future in EMEA July 2008 – only electronic submissions accepted (either eCTD or non-eCTD) July 2009 – strongly recommend only eCTD format electronic submissions to be accepted. Paper and other electronic formats to be exception.

5. SAPRAA 5 Sept 2008 Why go electronic? Quality Better quality Entire life cycle of product covered Easy and rapid call up of information Costs Paper and transportation costs reduced Storage and archive requirements reduced Faster, more efficient review, quicker registration Environmentally responsible

6. SAPRAA 5 Sept 2008 Save a tree!! NCE is approx 240,000 pages Paper for this would be 672 kg Equivalent to ONE average tree AN ENTIRE TREE IS REQUIRED TO SUBMIT A SINGLE COPY OF THE APPLICATION FORM ONE APPLICANT TO ONE HEALTH AUTHORITY

7. SAPRAA 5 Sept 2008 Types of electronic submissions NeeS format (Non eCTD electronic submission) Scanned version of paper submission without backbone etc. eCTD Documents in ‘intelligent’ PDF, JPG or GIF format, with folder or tree structures and XML backbone

8. SAPRAA 5 Sept 2008 What does eCTD consist of? Folder or tree structure XML backbone file is Table of Contents Additional ‘util’ information (Document type definition – rule book for tags and attributes) Regional information and files

9. SAPRAA 5 Sept 2008 Folder Structure Sections with specific information in folder names

10. SAPRAA 5 Sept 2008 Preparing documents Templates should be used where possible Documents to be: technically correct have the right granularity conform to external regulations/guidelines consistent with internal standards and styles – naming conventions, etc. ‘intelligent’ PDF files

11. SAPRAA 5 Sept 2008 From eCTD Fundamentals Dr O Schoepke

12. SAPRAA 5 Sept 2008 Granularity Defines how the completed document is broken down, tagged and stored for reuse Determines smallest piece of information that is reusable Changing granularity during lifecycle is difficult, therefore must be planned at the beginning. FDA Guidance Each document should be provided as a separate file

13. SAPRAA 5 Sept 2008 ‘intelligent’ PDF files A file converted to special PDF format enabling links and bookmarks to be applied, and hence is searchable.

14. SAPRAA 5 Sept 2008 Cross referencing documents Intradocument links – bookmarks Most intradocument links can be automatically set using templates To set each link manually would take MANY hours Interdocument links Cross reference documents in context of other documents.

15. SAPRAA 5 Sept 2008 Cross referencing submissions Inter submission links Cross references of submissions in context of other submissions, e.g. variations.

16. SAPRAA 5 Sept 2008 Time frames Once all documents are written, checked and formatted setting bookmarks and links take from 2 to 12 weeks.

17. SAPRAA 5 Sept 2008 Eye openers Global application Life cycle history easily accessible Ease of compilation and review once system is up and running Intersubmission checks made possible by both applicant and reviewer Authenticity of documentation easy to verify.

18. SAPRAA 5 Sept 2008 Bombshells Extensive software programme needed to support the system Software programme used in EU costs €20,000 per USER (over R200,000 per user) Extensive IT support needed by applicant and regulator

19. SAPRAA 5 Sept 2008 Conclusion Great idea but need intermediate steps to get there CTD format to be adopted immediately NeeS in interim Essential to join electronic bandwagon