1. GIQAR - Marzo 20051 VESMS Validated Electronic Spreadsheets Management System Marino Gobetti Information Communication Technology QA Nerviano Medical Sciences

2. GIQAR - Marzo 20052 Business needs Validated Excel Spreadsheets Pfizer audit observation Many FDA 483s on the subject Spreadsheets 21 CFR Part 11 compliant Security & Data protection Audit trail E-Signature

3. GIQAR - Marzo 20053 Options From Vendors – DaCS (Data Compliance System) – NuGenesis ® SDMS – Scientific Software ® RSME In-house development – First experience of development of a GXP computer system in Nerviano

4. GIQAR - Marzo 20054 Pros and Cons In-houseVendor CostLowHigh Implementation time LongShort CustomizationEasyCostly FlexibilityHighLimited Validation Development Compliance Spreadsheets Compliance Spreadsheets Integration with current systems YesNo

5. GIQAR - Marzo 20055 Goals  Excel Spreadsheets Validation  Integration of Excel Spreadsheets within IDARS System

6. GIQAR - Marzo 20056 Excel Spreadsheets  Excel Spreadsheets (Not validated) Enforce procedural controls Limiting functionality (menu/button/shortcut key) Macros to enforce controls Event handlers (open, close, print, save, etc.) Password protection VBA macros, Charts, Cells, Objects No audit trail No Excel file creation

7. GIQAR - Marzo 20057 IDARS IDARS system (Validated archive system) IDARS permissions and roles Read-only files E-sig on PDF files Version-based audit trail

8. GIQAR - Marzo 20058 Flow Diagram e-rec + e-sig Development Excel Spreadsheet *.pdf file*.xls file (master copy) *.pdf file + e-sig IDARS *.xls file master copy Data entry *.pdf file e-sig

9. GIQAR - Marzo 20059 Validation Strategy Compliance Functionality Spreadsheet Functionality Increasing Cost Full ValidationCompartmentalized Validation Standardizing the compliance functionality allows you to validate that part once only. It does not need to be repeated for each spreadsheet. You just need to do a minimal amount of compliance testing to demonstrate the individual spreadsheet works in that environment. With a large number of spreadsheets, the savings can be substantial. One Spreadsheet Compartmentalized Validation

10. GIQAR - Marzo 200510 Validation VESMS went through a full Computer Validation cycle satisfying all the 12 elements of the QA Standard 0036 Project analysis Spreadsheet designSpreadsheet development System test Project plan Validation plan System design System development Maintenance Implementation Spreadsheet test

11. GIQAR - Marzo 200511 VESMS Features  VESMS is a modular system made of a common basis and separate Excel applications for each type of calculation  VESMS relies on the IDARS system for a secure and validated data archival  Users work on validated unchangeable Excel templates; generate, store, and sign only PDF files

12. GIQAR - Marzo 200512 VESMS Benefits Validated macros and formulas Standardized calculation and reporting Comprehensive and consistent output No need to double-check calculations e-Rec / e-Sig compliant with 21 CFR Part 11 Effective and efficient archiving system Easy retrieval of previous results Easy sharing of results No qualification needed for client PCs A step towards paperless workflow Minor validation effort for new spreadsheets

13. GIQAR - Marzo 200513 Timelines & Resources Start date 19 May 2004 Implementation date 16 November 2004 External costs (dev. and val.) = 0.00 € No additional maintenance cost for the future 20 Acrobat licenses: 5700 € (licences also available for other applications)

14. GIQAR - Marzo 200514 Conclusions All Departments, in any Business Unit, that need to use Excel spreadsheets to perform repeated calculations in a validated environment can develop specific spreadsheets to be included in VESMS system. The data are e-Records with e-Signature compliant with FDA 21 CFR Part 11 and can be used for any internal and external regulated activity.

15. GIQAR - Marzo 200515 Consultancy VESMS Team is available for consultancy.......on demand VESMS Team