1. www.diahome.org Business Considerations in eTMF Implementation Karen Roy Phlexglobal Ltd.

2. www.diahome.org Agenda Defining eTMFs Why implement an eTMF? F-A-B Implementation process Workflow change requirements Role impact Who has an eTMF or one in implementation ?

3. www.diahome.org The Integrated eTMF Vision Data Management Clinical Operations Investigators Pharmacovigilance Regulatory and Ethics Clinical Supplies Service Providers

4. www.diahome.org The eTMF Challenge

5. www.diahome.org Why not keep just paper? Paper = lack of visibility Paper = travel to review Paper = variation and replication Paper = lack of management oversight Paper = no regulatory benefit Paper = risk (business continuity) Paper is the least effective way to store information requiring access The cost of discovery of a piece of paper is $1

6. www.diahome.org Regulatory compliance –Scanning Duplex 300dpi WORM data eTMF System Requirements Scanning WORM Export Image Enhance /Split Image Enhance /Split QC (AQL Percentage) ‏ Saving Move to WORM Media Rescan QC failure Paper Preparation Paper re- filing

7. www.diahome.org Regulatory compliance (21CFR part 11) –Compliant scanning process (duplex, 300dpi, WORM data) –Validated system –Compulsory audit trail –Locked down documents Secure and restrictable access Consistent indexing parameters Quality controlled process www access Search facility eTMF System Requirements

8. www.diahome.org The eTMF Deliverable Management tool Flexibility to workflow requirements One centralised and consistent TMF 24/7 www visibility Secure electronic back-up Not just an electronic repository!

9. www.diahome.org The eTMF Benefits Increases company efficiency Strengthens business continuity Improves inspection readiness Increases global visibility Improves vendor partnerships

10. www.diahome.org eTMF Implementation Success Factors Executive level support Cross-departmental support eTMF Governance Committee –Quality Assurance, Clinical Development, Data Management, Pharmacovigilance, Medical Affairs, Regulatory Affairs, Records Management Workshops Operational Review –Systems, records, stakeholders –Workflow analysis

11. www.diahome.org Workflow and Practice Analysis Pre-trial setup Project planning Feasibility Resourcing Project planning Feasibility Resourcing Trial initiation Approvals Supplies D/b setup Approvals Supplies D/b setup Trial conduct Monitoring Safety reporting Monitoring Safety reporting Data management Data cleaning Data analysis Statistics Data cleaning Data analysis Statistics Trial closure Data, drug & document reconciliation Trial reporting CSR Safety reports Regulatory reports CSR Safety reports Regulatory reports Quality gates / Quality criteria Document handoffs Regulatory, legal & business requirements Process optimisation / efficiency Inspection readiness / litigation support / due diligence

12. www.diahome.org Define an Efficient Workflow! Regular document submission Regular on-line review No keeping of duplicates Rely on electronic review

13. www.diahome.org The Business Impact on Quality Highlighting missing documentation Ensuring correct version available Expiry of documents Increased security around access (read-only) Improved oversight and review

14. www.diahome.org The Business Impact on CRAs Reduced travel to review Increased accessibility to documentation Correct versions available centrally 24/7 www access Ease of locating documents Remote download and print

15. www.diahome.org The Business Impact on Project Managers Reduced travel to review Increased oversight Two-dimensional search ability

16. www.diahome.org Search Ability with 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

17. www.diahome.org Example Indexing

18. www.diahome.org The Business Impact on Project Managers Reduced travel to review Increased oversight – Two-dimensional search ability - ease of location of documents – Quality of documents – Staff and subcontractors oversight – Flow of submission of documents – Flagging of drug release documents – Audit trail of activity - reporting module

19. www.diahome.org The Business Impact on TMF Managers Storage room requirements reduced No duplication Consistent filing Documents easily located No reconciliation Secure controlled access to electronic and paper Flexibility to requirements e.g. version control, expiry dates Flexibility to workflows e.g. QC

20. www.diahome.org The Business Impact on Regulatory www.xxxxx.com SSL certified https://www.xxxxx.com SSL certified Paper preparation and Scanning Indexing according to TMF structure Document Creation (DMS) or eCTD publishing package Secure TMF storage Only 5 to 15% of scanned documentation is required by Regulatory

21. www.diahome.org The Business Impact on Outsourcing Improved CRO oversight Payments linked to productivity e.g. MVR Ease of change of CRO TMF management costs can be stripped from budgets Overall cost impact reduced through other savings: –CRO TMF management –Storage –Travel –Duplication –Reconciliation

22. www.diahome.org The Overall Business Impact Secure electronic back-up (Business Continuity Plan)‏ Improved CRO and staff oversight Improved quality More compliant TMFs Significant travel cost savings

23. www.diahome.org Summary Paper Trial Master Files have significant issues eTMFs  simplify & improve clinical trials administration saving both time and money  improve quality  support business continuity  assist in making TMFs inspection ready  provide an invaluable management tool  support regulatory applications

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