Christine McGrath Research and Development Manager (Governance & Quality) Diana Benton

1. How to survive a MHRA GCP Inspection Experience of a non-commercial organisation Christine McGrath Research and Development Manager (Governance & Quality) Diana Benton Research and Development Project Manager Department of Research & Effectiveness United Bristol Healthcare Trust

2. Surviving an MHRA inspection Be prepared! • Why us? • What happened? • Pre-inspection • During inspection • Post inspection • UBHT findings & responses • How can the MHRA help?

3. Why UBHT?

4. Pre-inspection Advanced Notice of MHRA Statutory GCP Inspection ‘To examine compliance of the systems used by UBHT for conducting clinical trials’

5. The Dossier Identify clinical trial activities performed at: • UBHT • Alternative location – relevant to UBHT

6. Activities

7. Activities at UBHT

8. At alternative location

9. At alternative location

10. Alternative Location Public health labs Database company ICH GCP trainers UBHT R&D Pharmacy Information & Technology Radiology Laboratories Research and Development Support Unit Medical Records Departments involved in activities Trust-wide

11. Trust Board Clinical Directors Research leads PIs IMP studies General Managers Relevant staff Research teams Communication R&D

12. Documentation • Organisation charts – each department • SOP index • SOP on production of SOPs • Detailed SOPs relating to: • Management/supply of IMPs (drug accountability, formulation, packaging and labelling routines) • Clinical Trial Management • Quality control and assurance • Computerised systems (purchase, implementation, evaluation/validation, back-up and disaster recovery plans) • Equipment maintenance, calibration and servicing routines • Laboratory procedures (validation methods, sample chain of custody, logistics) • Descriptions of archiving arrangements • List of clinical trials

14. Draft inspection plan Arrange inspection visits • Departments • Staff • Individual studies • Protocols • Patient recruitment • Availability of PI

15. Final inspection plan Day 1 • Open meeting • R&E Department • Medical records • Pharmacy • IM&T Day 2 • Study 1 • Study 2 • Study 3 Day 3 • Laboratories • Haematology • Clinical Chem • Histopathology • Microbiology • Radiology • Closing meeting

16. Time and events schedule

17. Interviews with staff Review Documents Facilities Computer systems Requests Additional documentation The Inspection

18. Staff R&D Manager (Governance and Quality) R&D Information Officer RDSU Co-ordinator Systems Project approval Identification of sponsor Ongoing trials New trials Pharmacovigilance Monitoring Training resources GCP Training Research Governance leaflets Web site Newsletter Facilities Computer network Filing & Archiving R&E Department Could not guarantee all ongoing and new IMP studies have adequate sponsor Inadequate AE and SAE/SUSAR reporting systems.

19. Staff Health Records Managers Facilities Filing & Archiving Computer network Systems Security Confidentiality Tracking Archiving Destruction When? How? Quality Assurance Medical Records Study documentation not in secure places with restricted access.

20. Staff Director of Pharmacy QA Manager Pharmacy Technician Facilities Pharmacy department Parenteral Services Unit Storage facilities Freezers Systems Project approval Prescribing Process Documentation Chain of custody Unblinding Pharmacovigilance Quality assurance Pharmacy

21. Systems Procurement Validation/evaluation Conduct/user acceptance testing Decommissioning Archiving Disaster recovery plan In-house databases Security Confidentiality Information Technology Staff • Director of IM&T • Information Governance Lead • Lack of Trust wide validation /evaluation of computerised systems • Disaster recovery plan in development • Lack of security and confidentiality on local systems

22. Systems Project approval Chain of custody Quality control Laboratories Staff • Chief MLSO • Head Biomedical Scientist Facilities • Analysers • Freezers • Computer systems • Back-up Inadequate retention of evidence of QA and QC • Lack of Trust wide validation /evaluation of computerised systems

23. Systems Project approval Requesting investigations Reporting & recording Accessing films Archiving Radiology Staff • Professor of Radiology • Superintendent Radiographer Facilities • MRI suite • Computer systems • Storage Inadequate retention period Inadequate retention of evidence of validation for alternative media used to store records

24. Study conduct Essential Documents Completeness Version control Consent Process Documentation Prescribing and dispensing IMT AE and SAE reporting Studies • Lack of evidence of GCP training • Involvement of PI variable & not documented • Delegated responsibilities not clearly documented Staff • PIs • Research Staff Poor document control Original copies of consent not available for all patients. • Lack of awareness of (S)AE/SUSAR reporting requirements

25. Closure meeting • Open to all involved in inspection • Feedback of general findings • No surprises!

26. Post-inspection 3 months Response required - 28 days January 2005

27. New systems Securing UBHT as Sponsor SOP • Protocol template • Standard wording (indemnity, GCP statement, data protection, archiving) Adverse event policy • AE recording form • SAE / SUSAR reporting form Monitoring SOP • Site file • Approvals • Delegation • GCP training • Archiving arrangements • Consent • Adverse events

28. New training resources In-house GCP training courses • 1 day ‘ICH GCP’ • 5 day ‘Good Practice in Clinic Research 2004’ Information sheets • Guidance to writing a protocol • Amendments • SAE/SUSAR reporting • Responsibilities of a CTA holder Templates • Site file • Delegation log • Screening and recruitment log • Tissue retention log

29. www.ubht.nhs.uk/r&d

30. How can the MHRA help? • More notice • Min 6 weeks for Consultants • Better guidance on dossier • More tailored to NHS • Exemplar policies / SOPs / Forms • Adverse events • Monitoring • Guidance on common inspection findings • Electronic copy of Inspection Report

31. How to survive? Before • Clear systems and standards • Trust wide • MHRA compliant • Provide accessible training • Monitor During • Trust-wide approach • Good communication • Open, honest and helpful After • Don’t become complacent!

32. Never stop thinking ……. MHRA