Are we ready for an audit/inspection as a CRO? Clinical Research Association Istanbul – 01DEC2007

1. Are we ready for an audit/inspection as a CRO? Clinical Research Association Istanbul – 01DEC2007 Tony Owen, Vice-President QA Europe

2. Content • What are my credentials? • Quintiles Experience • When do you start preparing? • Quality Management System • Who’s your best friend internally? • Internal QA programme • What to do when the inspection is announced? • Preparation for audit/inspections

3. 1999 – 5 2000 – 16 2001 – 21 2002 – 26 2003 – 41 2004 – 23 2005 – 13 2006 – 42 2007 – 60 2006 first inspection in Turkey FDA Investigator Site Inspection No FD483 Quintiles- Inspection Experience in Europe (2007 to date) Inspectors are like busses! You never know when the next one will arrive!

4. Quintiles inspection experience- With various inspection agencies (end 2Q07)

5. Quality Management System When do you start preparing for an inspection? “There is no time like the present.” • Regulations • SOPs • Training and development • Validated computer systems • Management oversight • Quality Control • Quality Assurance • Records of all the above

6. Internal QA Programme • QA - Service function • QA Services • Audits • Metrics • Quality Issue management • Consultancy – quality related queries • Host customer audits/ regulatory inspections • Training (some) • Quality Planning • QA Leads QA is your best friend!!!

7. Internal Audit Programme • Audit All Pivotal studies • As a minimum: • Quality Planning Team meetings • In Trial • 2 In Depth Site Audits per project • Additional projects can be included in the internal audit programme as deemed necessary by QA. • Non-pivotal studies - occasional telephone audits • Process and computer systems audits Internal audit programme to complement the sponsor audit programme, not replace it

8. Audits - Do different types to drive improvement e.g.: • Scorecard audits • Select Key Performance indicators • Audit across offices • Score the results and publish • Develop action plans • Repeat to drive improvement • Telephone audits • Interviews with groups of CRAs • Set questions • Publish – this is what you need to know about your st

9. Average for Last Four Quarters, Q2 2006 to Q1 2007 (European Average = x) No of Reports Average No of Findings 0 Metrics - Make the most of information you have • Collate audit data • Enter into a database • Produce regular operational metrics • Analyse findings – introduce preventive actions • Drive improvement

10. Quality Planning- Prepare for inspection before study starts! • QA, PM, CTL, Medical Advisor, Regulatory Affairs, others • “What could kill this study in an inspection?” e.g.: • Cannot demonstrate correct diagnosis • Efficacy measures inconsistent • Supplies not stored correctly • Identify the risks e.g.: • For each key diagnostic, efficacy and safety test • What equipment/experience is required? • How will this be communicated and documented? • What consistency checks are required to be performed? • What evidence will be required? • Mitigate the risk • Plan, instruct, monitor correct

11. What to do when an inspection is announced! • Prepare sometimes - It’s not always sensible/possible! • Low risk • Brief investigator site inspections • e.g. Germany, Greece, Hungary, Bulgaria • Intermediate risk • More intensive site inspections, may include visit to sponsor/CRO facilities • e.g. France, Italy, Finland, Ireland, Austria • High risk • Intensive, sites and sponsor/CRO facilities • Evaluation of sponsor/CRO processes • Can extend into other parts of business • e.g. EMEA, FDA, UK-MHRA The last chance saloon!

12. A Possible Strategy for Inspection Management

13. Quintiles Preparation -Intermediate and High Risk Inspections • QA pre-inspection (as soon as possible) • Focus on processes, computer systems, and projects • Interview staff and review documents • Agree action plan • Follow up on actions • Place third parties on stand by • Train staff in handling inspections • Encourage staff in their knowledge and abilities

14. Thank you!