DIA 6 th European Validation Workshop, Amsterdam, 2007.

1. Building Change into Process David Bridges Director, eChange Solutions Limited DIA 6th European Validation Workshop, Amsterdam, 2007.

2. Introduction • Impact of change on validated systems • How to manage change • Contrast with processes and recourses used in new system introduction / major upgrades. • Drawing examples from the European Biometrics Department of an (un-named) global research based pharma. Company.

3. Image Management Biometrics systems Query Management Reporting & Statistical Analysis Submission Compilation & Publishing RDE CDMS Work Tracking Resource Management

4. Biometrics systems Query Management Reporting & Statistical Analysis Submission Compilation & Publishing RDE CDMS Image Management Work Tracking Resource Management

5. Image Management Biometrics systems Query Management Reporting & Statistical Analysis Submission Compilation & Publishing RDE CDMS Work Tracking . Resource Management

6. Major System Change Query Management Query Generation CDMS Reporting & Statistical Analysis RDE Data transfer Data Extraction Data entry OCR Image Management Major change is usually focuses on a single system and it’s interfaces

7. CDMS System introduction / major upgrade Scope : • Requirement • Design • Development • Testing • Training • Release • Support planning Validation

8. CDMS System introduction / major upgrade Usually : • Organized as a project • High level sponsorship (business & technical) • High visibility • “Business” involvement • Best practice in • Change management • Configuration management • Risk management May also : • Form part of a change programme • Benefit from project office

9. Validation of system Query Management Query Generation CDMS Reporting & Statistical Analysis RDE Data transfer Data Extraction Data entry OCR Image Management Validation focuses on a single system and it’s interfaces

10. Validation paradigm Investigator FDA A chain of validated systems : Each of which has been validated to demonstrate its fitness for purpose. That together ensure the authenticity, integrity, confidentiality and signer non-repudiation of records from the investigator to regulatory authority.

11. So What is the problem ! • These system do not exist in a static environment. • In fact, the environment is less “under control” that the systems ! • Changes to : • Organization structure • Staff • Processes (SOPs) • Use of system • IT infrastructure • System functionality (minor changes, bug fixes) • All have potential to compromise the effective operation of the system.

12. Scale of change : Biometrics Biometrics involved with drugs in phase 1-3 & also drugs where primary submission complete but further submission (country, indication) required. • At any one time involved with approx. 20 drugs. 4 in phase III and a further 4 post primary submission. • Estimated duration of involvement with drug that is approved is 15 years I II III Post Submission

13. Think about it ! • What changes have occurred in your organization in the last 15 years ? • Organization structure • Staff • Processes (SOPs) • Use of system • IT infrastructure

14. System Duplication • Systems change but data migration is risky and expensive • This leads to system duplication

15. Managing change Management of change to : • Organization structure • Staff • Processes (SOPs) All require similar processes and resources • Change management • Configuration management • Risk management • Use of system • IT infrastructure • System functionality (minor/bugs) • Change control boards • Designated staff • Inventories • Decision makers

16. Managing change Management of change to : • Organization structure • Staff • Processes (SOPs) All result in similar outcomes • Document and proceed • Undertake partial risk-based validation • Undertake full validation • Use of system • IT infrastructure • System functionality (minor/bugs)

17. Analysis of validation events Over a three year period there were 41 changes to systems or processes requiring full or partial re-validation impacting the Clinical Data Management System (CDMS). Half related to upgrades of the CDMS system itself, while the remainder related to auxiliary systems and infrastructure products such as the database, SAS and the operating system.

18. Analysis of validation events Of the 41 events • 11 were infrastructure driven : • 4 database • 9 Server • Of these 2 were driven by infrastructure change required by another validated system • 2 were database migration projects • 12 were releases of new functionality (including bugs) • 16 were bug-fix releases • Significant number of infrastructure and process deemed not to require re-validation by CCBs.

19. Final points • Can not achieve compliance by focusing on change management of the system alone. • Most organizations have multiple CCB’s (& they don’t talk to each other !). • One man’s focus of responsibility is another man’s risk.

20. Practical advice • Determine what the sources of change are and how they are controlled • Encourage best practice within each domain • Encourage communication and mutual support • Put in place safety net (Support Plan)

21. Questions ? Many Thanks Slides can be downloaded from : www.echangesolutions.com from Monday Or leave me a business card and I will e-mail them to you.