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 #1 Long Term Preparations

4. Agenda • AIPP Program • Session Objectives • Types of Audits • Who Audits and Why • Selection Criteria • 10 things to Do for Long term preparedness • Questions and Answers

5. Audit Inspection Preparedness Program (AIPP) It approaches quality and compliance through audit education and planning. Research staff have access to: • training session • mock audit exercises • written resource • opportunity to develop long term and short term preparation compliance plans

6. Objectives of the Session Increase research team’s comfort with preparing for an audit Promote compliance Introduce compliance management and quality management concepts

7. Types of Audits Routine or Random Targeted or Directed For Cause Auditors and regulatory authorities also do Verifications. Regulatory authorities do Investigations.

8. Who Audits? Regulatory - Domestic (Inspection) Qualification REB Vigilance Sponsor (pre, during, EOS, data) Internal or Institutional Foreign Joint Foreign

9. Why do they Audit Ensure participants safety and rights are protected Ensure quality integrity and accuracy of data Ensure compliance with regulations, institutional policy, best practices, industry standards and institutional expectations, REB requirements

10. Selection Criteria All agencies that audit have a policy or a manual that outlines their selection criteria. There is a full description of common selection criteria in the AIPP Manual.

11. 10 Things to Do to for Audit Preparedness

12. 1. Long Term Audit Preparation Plan Document – checklist format outlining long range preparation items Reviewed 3 to 6 months Class: working internal document

13. 2. Compliance Education In order to be prepared you need to know what you are supposed to be compliant with: • Regulations (research and privacy) • Policies (institution, granting agencies, REB) • SOPs • Jurisdiction(s) • Current Guidance Documents • Audit trends

14. Compliance Post external audit or inspection or investigation is not a good time to discover that you are non compliant. Complacency is another issue that arises.

15. Compliance Education Mentorship Training - Initial and Ongoing • Division 5 (Canada) • Specialty subsection (medical device, biologics, radiopharmaceutical, combination products) • Canadian regulatory environment • GCP update annual with audit trends • Documented training on study area

16. Compliance Training Courses through BCCRIN • CITI Certification • SoCRA • ARCP TCPS Training (required for studies sponsored by CIHR etc) US, EU, Japan Regulatory Environment Country Specific GCP Training

17. 3. Standard Operating Procedures SOP for each procedure conducted at your site or organization Policies , working practices, forms, and templates to support SOPs Missing SOPs that have been identified should be noted in a Compliance Development Plan (CPD)

18. 4. Controlled Document Listings Listing (index) of all current controlled documents Most auditors will request this before an audit All obsolete SOPs, policies, WP’s, forms and templates should be listed as well The listings should include: • Title • Number (if applicable) • Version • Effective/Obsolete Date

19. 5. Quality Systems Quality Systems should be in place, maintained and functional. • Document Management (Overview, CC, Annual Review, External Distribution, External Document Registration) • Training • Deviation, CAPA, Observation • CQI • Auditing, Vendor Qualification

20. 6. Collection/Location of Documents Determine whether there are any pertinent documents located off site or in other offices. Examples of documents commonly missing: • Statements of Compliance (i.e. computerized systems) • Validation Documentation • Security Documents (reasonable protection of study)

21. Collection/Location of Required Documents • Reports – can you provide them on short notice (arrange for programming) • Transfer of Responsibility document • Closed study documentation (logged and obtainable) • Audit History • Study Signature Sheets • Access Logs (guest registry, restricted rooms, computers)

22. 7. Items for Demonstration Areas that needs the most advance preparation Consider what an auditor will want to see Review your procedures/systems/processes Identify the items that would likely need to be demonstrated to prove that they are effective and function as they should. Select samples to show your system is effective. Write them down.

23. Items for Demonstration Examples: • Data Management Procedures • CQI system • Deviation/CAPA System • Handling of Investigational Product • Administration of Informed Consent • Audit Trail • Privacy Impact Assessments – data flow component

24. 8. Audit Kit Prepare an Audit Kit so that you have the materials ready to conduct an audit at any time. Assign someone to be responsible to check the kit at least twice per year. Make sure that all current editions and recently updated items listed are added to the kit.

25. Audit Kit Items to put into your Audit Kit: • Contact Numbers for persons that need to be notified of the audit (management, sponsor, medical records, communications, QA, storage) • Welcome procedures (how to take credentials and do a guest registration) • Roles of Audit Personnel • Form & Instructions for Document and Record Control

26. Audit Kit Items to put into your Audit Kit Cont’: • Organizational Chart (current & past versions) • Site map (current and past versions of all locations) • Site or Research Team History (brochure or write-up) • Audit History • Disposable Camera • Pens (6) Black or Blue, indelible ink • Lined Notebooks for Facilitator and Scribe (6)

27. 9. Audit Training Review the audit team member roles Review the rules of audit conduct. All personnel should be trained in audit conduct and the major Do’s and Don’ts Review the audit process and four phases (readiness, preparation upon notice, hosting an audit and audit follow-up)

28. 10. Compliance Assessment Internal Audit/Review Compliance Review with a Compliance Specialist These types of reviews are educational in nature. Reports from an internal audit or compliance review will assist you to develop compliance development plan (CDP)

29. Compliance Development Plan (CDP) Prepare CDP to address anything idenfied in a compliance assessment: Identify items missing or requiring revision • Date entries • Title • Expected date of completion • Person responsible Identify any new Training requirements Can work in conjunction with a Long Term Audit Preparation Plan

30. Thank You --- Questions and Answers

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

32. 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.

33. 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