1. 1 Building an eSubmissions System Ed Tripp Program Director Abbott Laboratories

2. 2 Pharmaceutical Drug Applications Typical drug product is 10 years in development Must apply for approval by Regulatory Authority (such as FDA) before marketing Must show both safety and efficacy Typical approvals approximately 1 year after submission Exclusivity determined by patent life

3. 3 Size of a Submission 10 years of data and document Typical 1,000 volumes In paper that stack is 16 stories tall 7 to 20 gigabytes of documents and data Reviewer expects to be 3 mouse clicks from any data Heavily bookmarked and hyperlinked

4. 4 Cost Model Average Drug ends exclusivity at about $400MM/year Delay in submission approval compresses curve Cost of delay $1MM per day ($12.68/second)

5. 5 Key Documentum Functions Workflow and Electronic Signature Speed and Accuracy Organization (Indexing/Folders) Key to putting together successful NDA for the FDA Security regarding Documents Patient Records – Insider Information Multiple document types Word, Excel, SAS, Image, + others all need to be combined in a easy to read format

6. 6 Current State? How do you store documents and data and how do you process Submissions?

7. 7 Source Documents Check all that apply CMCClinicalNon clinicalRegulatory DMS File share Local discs Paper system Are your Document Management Practices –Well documented? –Disciplined? –Ad hoc? How are they managed today?

8. 8 Source Documents Check all that apply CMCClinicalNon clinicalRegulatory US EU Japan Canada Caribbean India China Where are they located?

9. 9 What Will You Keep in the Submission System? A. Only documents to be submitted? B. Documents that may be submitted? C. Submission and Trial Master file documents? D. Documents and data sets? E. XML Labeling? F. All of the above

10. 10 Submissions: What Regions Will Be Supported? US EU Japan Canada Australia Others? For Submissions? For Document Management?

11. 11 Submissions: What Process Do You Currently Use? Submissions in Paper Printed from electronic files Xerox and Paginate Submissions Electronic eCTD eNDA eBLA eIND Other electronic formats What do you want to support with your new system? Submission types Products: Only Drugs? Include Vet Meds? Device?

12. 12 Migration Will you be migrating documents into the new system From retiring docbase? From File Share? From Local Files? From system you acquired? Migration can be 10%-20% of your total project cost!

13. 13 Security Model Who has access in the new system?

14. 14 Document Based By Document Most management overhead Who Decides? By Doctype State Clinical Ops ClinicalCMCRANon Clin DraftVersionReadBrowse ApprovedRead SupersededRead ObsoleteBrowseNone Example: ClinSupply Doctype

15. 15 Function Based Security All in function have same rights Example: Everyone in clinical function can view and edit draft documents Moderate number of groups to manage Provided you think of functions broadly Harmonize processes where possible

16. 16 Role Based All in a given role have same rights Example: State AuthorReviewerApprover DraftVersionRelateRead ApprovedRead SupersededRead ObsoleteBrowse

17. 17 System Ownership Most documents by created by R&D Submissions responsibility of RA Typical percentages

18. 18 Deployment How do you deploy the system? Thick Client? Thin Client? Application Delivery Software? Do you deploy the same way everywhere? What is your enterprise bandwidth for each site?

19. 19 Document Repository Structure How to best configure a for users?

20. 20 Document/Folder Structure By Product? How development thinks and works By Submission? How regulatory thinks and works Who creates structure? IT request? User tool to create from a template? Created from metadata?

21. 21 How Many States? Draft Formatted Reviewed Routing Approved FDA Approved Superceded Obsolete

22. 22 How Many Different Lifecycles? Labeling Correspondence Submission documents Data sets Templates Compiled publications Virtual Documents

23. 23 How Will You Handle Draft Versions? Deletion on approval or retain? Start with v0.1 or v1.0? Does a change in properties trigger a new version?

24. 24 Will You Use Electronic Signatures? Is an eSigned document identified vs non signed but approved document? Will you use SAFE? Will you use UID and Password?

25. 25 Do All Documents Process Through Workflows? Can you delegate a workflow? Can priorities be assigned? Can you add workflow participants? What will trigger user notification? When they have a task? When documents become approved? When documents change state? When one person rejects a document?

26. 26 Workflow Considerations Can you include multiple documents? Will multiple documents have individual outcomes? Can documents be promoted without workflows? Who can promote documents?

27. 27 Workflow Example

28. 28 What Will You Audit Trail? All actions taken? Approval functions only? Are audit trails available to the user?

29. 29 How Will You Handle Amendments and Errata? Do you need to change your current practice to version the whole document? How do you relate an errata page to the document? Do all both Clinical and Non Clinical have the same process?

30. 30 Can You Annotate Documents in Review? Can all reviewers see all annotations? Can you annotate off line? Do annotations get purged? When?

31. 31 Content Creation Scan Content OCR or not? Create with Templates Will you manage templates in the system Will you make them available outside the system Who owns the templates Create from blank Create from copy of existing Document Virtual Documents Import Content Are there document relationships

32. 32 Content Creation Continued When is a rendition triggered? Upon check in? Only if content is changed? Only when moving beyond draft state? What file formats? Who can create content? Who can edit content? Centralized Medical Writers?

33. 33 What File Types and Applications Do You Support? Documents MS Word (what version) Adobe Acrobat (FDA requires v1.4 PDF) XML Text files Graphics JPG Data SAS Transport XML Others? Need to specify application version and service packs

34. 34 Bookmarks and Hyperlinks Will your system create bookmarks from Word document styles? Training implications Who creates bookmarks for scanned documents? How do you create and manage hyperlinks? Internal to documents Cross document hyperlinks

35. 35 Where Will You Store a Submission? You need to publish to a fileshare Consider eCTD, other electronic submissions, files to generate a paper submission Docbase?  Do you want active links?  How do you move all folders and files? File Share?  Need a security process

36. 36 Metadata Management Its not just about the content

37. 37 Metadata Will you create a doc unique ID? You WILL migrate in the future, so think about a unique ID that does not change from Docbase to Docbase. Will you utilize value assist? Are there non required fields? Why? Can changes be made to metadata without versioning a document? Submission number may not be known at time of submission

38. 38 Will You Utilize Dictionary Files? Who manages the files? What is the update process? Are there relationships? Example: a Clinical Study has one Number and many investigators Document the authoritative source of terms ICH specification NCI EVS Thesaurus Snomed or Medra Other

39. 39 How Will You Use Metadata? Do you pass metadata to submission software? DocID for filename eCTD leaf title Species Indication Other STF metadata What metadata do you expose for searching Is the out of the box search tool sufficient Full text indexing? Is it worth performance issues? Do you need a reporting tool?

40. 40 External Interface Needs Do you work with Partners? Provide access to part of your system? Work through FTP? Internet Portal?  Who manages access and content?

41. 41 Internal Interfaces Bulk import solution Scanning solution Submission tracking system Commitment tracking system Email system Other docbases Rendering services Reporting tools Publishing software Will published submission reside in the docbase

42. 42 Training Considerations How savvy is your organization? How do they learn best? ILT CBT Webcasts

43. 43 Training Continued How familiar is the organization with electronic submissions? eCTD? Docbase related topics More complex Security Version Management Meta Data Search functions Authoring related topics Submission Ready Documents Template use Software restrictions

44. 44 Sample Architecture Future Integration: Submission Tracking CRF Tracking Internal collaborative space

45. 45 Build vs. Buy Not all configurations are created equal Configurations you can do internally Configurations that must be delivered What is your internal IT expertise? Do you keep up with releases or keep systems as is for several years?

46. 46 The Environment Is Not Stable eCTD r3.3.3 RPS r2 XML Protocols XML datasets SPL r4 Electronic clinical data capture Make sure you can react to changes for the next 5-8 years