VESMS V alidated E lectronic S preadsheets M anagement S ystem

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

2. 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. 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. Pros and Cons

5. Goals • Excel Spreadsheets Validation • Integration of Excel Spreadsheets within IDARS System

6. 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. IDARS • IDARS system (Validated archive system) • IDARS permissions and roles • Read-only files • E-sig on PDF files • Version-based audit trail

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

9. Validation Strategy Compartmentalized Validation Spreadsheet Functionality One Spreadsheet Compliance Functionality 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. Increasing Cost Full Validation Compartmentalized Validation

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

11. 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. 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. 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. 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. VESMS Team Consultancy VESMS Team is available for consultancy .......on demand