1. www.diahome.org Trial Master Files – the De-Centralised Communication Challenge Karen Roy

2. www.diahome.org Audience Demographics

3. www.diahome.org Agenda Defining TMFs eClinical and eTMFs eTMF variations and workflows eTMF Features Paper vs. eTMF Selecting an eTMF provider Paper forever?

4. www.diahome.org What is a TMF? ICH Section 8 – Essential Documents –Individually and collectively permit evaluation of the conduct of the trial and the quality of the data produced –Serve to demonstrate the compliance of the Investigator, Sponsor and monitor with the standards of GCP and the regulatory requirements –Defined filing structure Reality ? Paper, paper, paper...

5. www.diahome.org Paper vs. Electronic Document Generation Sponsors Ethics Committees Investigators Clinical & non-clinical supplies Regulatory Agencies Laboratories CROs

6. www.diahome.org External vs. Internal Document Generation (control) Sponsors Ethics Committees Investigators Clinical & non-clinical supplies Regulatory Agencies Laboratories CROs

7. www.diahome.org External clinical study report requirements Investigators Laboratories CROs Individual laboratory measurements Investigator and Co- Investigator CVs Principal Investigator Signature Audit certificates CRFs submitted

8. www.diahome.org Where is the TMF held? Project Management, Clinical Supplies Data Management, Statistics, Report Writing and QA. Regulatory Affairs Pharmacovigilance Clinical

9. www.diahome.org Who looks at a TMF? Project Manager Line Manager Project Team Auditor Document Manager

10. www.diahome.org Why do we need a TMF? ICH, EU Directive Volume 10, FDA Regulations, National Laws, Declaration of Helsinki, SOPs ICH GCP 8.3.11 requires the retention of –‘relevant communications that document any agreement or significant discussions regarding trial administration, protocol violations, trial conduct or adverse event reporting’ CTD and eCTD

11. www.diahome.org Paper TMF Issues De-centralised = lack of visibility Multiple isolated variable filing systems Replication of documentation Extensive travel for TMF review Hours of availability limited Oversight of CRA / CRO performance limited End-of-study panic filing (lack of compliance) End-of-study reconciliation

12. www.diahome.org e-Clinical is landing… EDC ePRO IVRS EHR and eSource CDISC ECG reading CTMS eTMF eCTD Wireless technology Laboratory Data Portal technologies E-Learning

13. www.diahome.org Define eTMF An electronic form of a paper TMF PDF / TIFF / word / excel / ms project Validated and secure (audit trail) Centralised but visible

14. www.diahome.org Define eTMF

15. www.diahome.org Integrated eTMF vision Sponsors Ethics Committees Investigators Clinical & non-clinical supplies Regulatory Agencies Laboratories CROs

16. www.diahome.org Example eTMF workflow (from paper & external) Paper preparation and Scanning Synchronisation Hosting Centre Indexing according to TMF structure Quality Control Paper Storage www.xxxxx.com SSL certified Document viewing www.xxxxx.com SSL certified

17. www.diahome.org Example eTMF workflow (internal) Document viewing www.xxxxx.com SSL certified www.xxxxx.com SSL certified Paper preparation and Scanning Indexing according to TMF structure Paper Storage Paper Printing Document Creation Indexing according to TMF structure

18. www.diahome.org Easy to use Flexible work-flows Flexible to TMF structure Indexing Advanced search facility www access Restrictions for CROs Quality controlled process eTMF desired features

19. www.diahome.org The Importance of Indexing Drug A EFGH ABCD Product No: Protocol No: File Type: CSF CIF 4 32 1 Centre No: Linked to Protocol No Section 1 2 5 6 4 7 3 8 10 9 11 14 13 12 15 16 Section 1 2 5 6 4 7 3 8 10 9 11 14 13 12 15 16 Monitoring Reports Sub Section Section 1 2 5 6 4 7 3 8 10 9 11 14 13 12 15 16 Sub Section Section 1 2 5 6 4 7 3 8 10 9 11 14 13 12 15 16 Sub Section Correspondence Monitoring Reports Dates of Synchronisation Dates of Documents

20. www.diahome.org Paper TMF vs eTMF De-centralised and variableCentralised and consistent No visibility24/7 www visibility No back-upSecure back-up (Bus. Continuity) Vulnerable during transitReduced transit Duplication and ReconciliationOne centralised TMF No shared information24/7 shared information No CRO or CRA oversightManagement tool – LM, PM, OM Extensive travelLimited or no travel TMF storage and management in- house Option to outsource TMF storage and management Have to copy in houseAbility to download and print Scanning required for CSROutput to CSR or CTMS

21. www.diahome.org Selecting an eTMF provider System release Quality Management System Computerised System Validation (CSV) Documented Testing Documentation standards in place (SOPs, user requirements, technical specifications, system maintenance) Staff training and training records SDLC approach for product Change control procedures

22. www.diahome.org Can we get rid of paper? Trends for paper review and filing Legal admissibility of Information stored on Electronic Document Management Systems (PD0008 and PD0009) –Compliance workbook –Focus across business procedures and processes, enabling technology and audit trails Legal standing / Regulators standing (Future readability of documents)

23. www.diahome.org Summary Paper Trial Master Files have significant issues Electronic Trial Master Files simplify & improve clinical trials administration eTMFs support business continuity eTMFs assist in making TMFs inspection ready eTMFs provide an invaluable management tool The Pharmaceutical Industry is embracing e-Clinical, why not eTMFs too?

24. www.diahome.org Thank You! Any Questions? Feel free to make contact on kroy@phlexglobal.comkroy@phlexglobal.com Or visit booth 408