BC Clinical Research Infrastructure Network

1. BC Clinical Research Infrastructure Network BCCRIN Changing the landscape for clinical research in BC. www.bccrin.ca

2. Lunch and Learn SeriesAudit and Inspection Preparedness Program

3. LL #4 Exit Meeting and Follow-Up

4. Agenda • Session Objectives • Exit Meeting • Quick Tips • General Audits • Inspections • Daily Review and Reporting • Team Meeting • CAPA • Follow-up • Questions and Answers

5. Objectives of the Session To increase the research team’s comfort with the exit meeting To introduce audit related follow-up requirements

6. Exit Meeting Arrive on time Everyone who was interviewed should attend Take minutes of the meeting Note who is in attendance, start time and adjournment Listen carefully This is your an opportunity to correct, clarify the information collected by the auditors

7. Exit Meeting – General Audits Lead Auditor will: • Review the purpose and scope • Go over the main sections • Point out strengths • Point out areas of concern and findings/observations • Probably state the classification system and the class of the findings in each area. • Indicate what they want corrected/by when.

8. Exit Meeting – Regulatory Only Review and make sure you understand each observation, correct any misunderstandings Negotiate timelines for CAPA HC – Exit Notice FDA – Form 483

9. Team Meeting Carefully review your audit notes and exit notices and any inspection reports and correspondence Team to meet to discuss follow-up actions for compliance Send a written response for any further corrections or responses to findings – do it within the timelines! Respond outlining corrective actions (CAPA) Conference with auditors/agency if necessary

10. Corrective and Preventative Action (CAPA) This system covers both corrective and preventative actions. ‘CAPA’ as it is coined, originated in the US Army in the 1930’s. CAPA is found in many industries. You should have a CAPA SOP. You need a CAPA Formand aCAPA Guidance Document (see BCCRIN AIPP form bank)

11. Corrective and Preventative Action (CAPA) Corrective actions are steps that are taken to remove the cause of a: • non-conformity (observation or finding) • deviation • undesirable situation Corrective Actions are designed to prevent the reoccurrence of the non-conformity or deviation by eliminating the cause. Corrective actions address actual problems It is a problem solving process

12. Corrective and Preventative Action (CAPA) Preventative actions are steps that are taken to remove the causes of potential non-conformities or potential problems. This process within the system is designed to prevent the occurrence of nonconformity by eliminating the cause.

13. Corrective and Preventative Action (CAPA) The system includes CAPA analysis root cause analysis and risk analysis. The CAPA system is linked to other Quality systems CQI and Deviation system. Corrective and preventive actions both include: investigation, action, review, and further action. It can be seen that both fit into the PDCA (plan-do-check-act) philosophy as determined by the Deming-Shewhart cycle.

14. Corrective and Preventative Action (CAPA) The BCCRIN guidance document outlines how to write effective CAPA’s. Written CAPA’s are reviewed and approved by supervisors and QA. CAPA progress is monitored Overdue CAPA, Open CAPA and Closed CAPA should be noted (staff meeting or report).

15. Post Audit Follow-up Complete all records and audit logs Complete any internal summary reports as required (institution specific) File audit documentation Update site audit history log Ensure CAPA completion

16. Ongoing Compliance Attend offered GCP update sessions, audit trend and influence sessions Address any known deficiencies identified in your site Compliance Development Plan Follow-up with any observations or findings from monitor reports or audits Complete CAPA

17. Ongoing Compliance Review your Audit Preparation Plan Maintain an Audit Kit Periodically review Training

18. Thank You --- Questions and Answers

19. Prepared for BCCRIN by: Jean SmartSmart QAS3375 West 26th AvenueVancouver, BCV6S 1N4Ph. 604-612-6372 email jesmart@telus.net

20. References Health Canada, Food and Drug Regulations, Part C, Division 5, Drugs for Clinical Trials Involving Human Subjects, (Schedule 1024), June 20, 2001. Health Canada, Guidance for Industry, Good Clinical Practice: Consolidated Guideline, ICH Topic E6, 1997. Health Canada, Health Products and Food Branch Inspectorate, Classification of Observations made in the Conduct of Inspections of Clinical Trials (GUIDE-0043), Revised Edition - August 29, 2008 Health Canada, Guidance Document - Annex 13 to the Current Edition of the Good Manufacturing Practices, Revised Edition - August 7, 2009 Health Canada, Guidance for Records Related to Clinical Trials (GUIDE-0068), Revised Edition - June 15, 2006 Health Canada, Health Products and Food Branch Inspectorate, Inspection Strategy for Clinical Trials, January, 2002 Health Canada, Health Products and Food Branch Inspectorate, Compliance and Enforcement Policy. No. POL-0001, May 30, 2005

21. References International Organization for Standardization (ISO), 9001:2008 - Quality Management Systems Requirements, ISO, 4th Edition, November 15, 2008, pgs 36. (replaced ISO 9001:2000) Pharmaceutical Inspection Convention, Pharmaceutical Inspection Co-operation Scheme, Annex 11, Computerised Systems, Edition September 25, 2007. US Food and Drug Administration, Compliance Program Guidance Manual, Program 7348.810, chapter 48, Edition: March 11, 2011 Office of Inspector General, Compliance Program Guidance. April 2003. Federal Register, Vol 68. No. 86 May 5 2003 Notices. European Forum for Good Clinical Practice - Audit Working Party, Revision of the Engage Auditing Guideline: An Optimal Guideline for GCP Compliance and Quality Management Systems Auditing, Engage publication, 2005. FDA Enforcement Statistics Summary Report 2008, Chapter 11. (Stats for 2004 to 2008). Jepson, Gordon. Consequences of Non Compliance in Canada. Regulatory Focus. January 2007.Vol 12 No.1 p 14-17.