Briefing on MHRA routine inspection of non-commercial clinical trials

1. Briefing on MHRA routine inspection of non-commercial clinical trials Routine Good Clinical Practice (GCP) MHRA Inspection, University of Aberdeen 2011

2. Aims • MHRA inspections • MHRA inspection at University of Aberdeen • How should staff prepare? • Advice for staff on key areas of weakness So that: • You can identify and address any actions required • You can participate in the interviews with confidence • University of Aberdeen can demonstrate that clinical trials are following current legislation and are conducted to high safety and quality standards.

3. Why do the MHRA Inspect? • EU directive 2001/20/EC transposed into UK law May 2004 as Medicines for Human Use (Clinical Trials) Regulations 2004 • Legal obligation to conduct Clinical Trials of Investigational Medical Products (CTIMPs) to Good Clinical Practice (GCP). • MHRA is statutory body responsible for compliance with UK regulations • MHRA inspect (CTIMPs) on humans covered by the regulations

4. 3 Types of MHRA Inspection • Routine • Triggered • Requested • University of Aberdeen inspection is routine • Provisionally 4 days week of 20 June 2011

5. Who do the MHRA inspect? • Legally able to inspect all organisations ‘sponsoring’ or ‘hosting’ clinical trials in the UK • Includes commercial and non-commercial organisations • Adapt inspection to organisation type • Routine inspections focus on systems

6. What do the MHRA inspect? • University has systems in place to support conduct of CTIMPs in compliance with regulations (and GCP). • Specific examples of CTIMPs to demonstrate those systems • Areas of interest include: • Approval processes and regulatory submissions • Contract Management • Trial file and data management • Quality assurance and monitoring • Training • IT systems • Pharmacovigilance • Archiving • Laboratories • Pharmacy

7. What happens before the inspection? • University notified by MHRA of inspection 4th February 2011 • Dossier sent to MHRA on 4th March 2011. Including a list of CTIMPs (live and complete) to give an overview of clinical trial activity. • MHRA provide draft agenda approx 6 weeks prior to the inspection • Teleconference to finalise agenda approx 2 weeks prior to inspection • University will coordinate the inspection

9. What are we doing to prepare? • MHRA Inspection Internal Working Group • Gap analysis and action plan • Monitoring and Audit • Informing staff of the inspection • Staff training – GCP

10. What are the key areas of weakness? • Qualifications and training • Communication • Delegation of duties • Standard Operating Procedures • Evidencing of information • Study file and filing • Pharmacovigilance • Informed Consent • Equipment • Study closure and archiving

11. Pharmacovigilance • Sponsor responsibility to ensure events are reported in accordance with regulations. • Currently have central reporting (documented in CI delegation letter) . • New SOP to be issued with updated process

12. Monitoring/Audit • Sponsored studies will be audited to ensure that essential documents are present in the Trial Maser File. • Training record will be required for trial personnel on a study delegation log.

13. Handout available with recommendations for addressing key areas of weakness. What can you do to prepare? SOPs for maintaining a Trial Master File, Investigator Site File, Pharmacovigilance will be available soon

14. What happens during the inspection? • Opening meeting – inspectors present inspection plan • Document review – including medical notes • Interviews with selected staff • Tour of facilities • Additional requests • Closing meeting – summary of findings and provisional grading

15. Interviews with study personnel on study conduct • These assess knowledge of GCP and regulatory requirements, and probe for evidence of robust processes for ensuring compliance with GCP • You should read through the example questions and answers provided.

16. Training Communication Safety reporting Protocol procedures & adherence Investigational medicinal product handling Informed consent Approval process including amendments Annual reports to ethics/MHRA Statistics and data handling Out of hours/leave cover Randomisation & un-blinding procedures End of trial & archiving procedures Common Themes During Interview:

17. Dos and Don’ts during Interview • Be honest - we know we have some gaps and are addressing them - failure to recognize the gaps is more problematic than acknowledging the gaps • Avoid being confrontational - esp. avoid giving the impression that this is ‘bureaucratic detail’ • Be ‘alert’ to areas of improvement • Avoid being defensive.

18. Dos and Don’ts during Interview • Only answer the question asked • If mistakes are made or wrong answers given, correct them at an appropriate time, or ensure somebody else does so. • Try your best to correct any deficiencies noted by the inspectors before they leave • Demonstrate confidence in your trial systems and data – you know it best. Be positive.

19. Dos and Don’ts during Interview • Should inspection findings be made, make sure that you understand them completely – it is easier to ask the inspector for clarification during the inspection rather than after the report is issued. • Don’t volunteer information • It is appropriate to challenge a finding made by an inspector if you are certain they are incorrect, but do not persist in your objection.

20. What happens after the inspection? • MHRA to report issues within 30 days of the inspection, summarising findings. • University response will include an action plan, timelines to address any findings. • MHRA receive response - will issue a closing letter and GCP Inspection Statement. • Future inspections will be performed at a frequency determined by the MHRA. • Possible routine GCP inspection of NHS Grampian

21. Summary • Review your trial documentation and training files for staff. • Have evidence of training (GCP certificate, CV) • Ensure you can explain your role in the trial • Review the typical questions and answers provided • Familiarise yourself with new SOPs when available • Be confident of your trial and processes. Remember that you know your trial better than anyone else.

22. Any Questions? Main Contacts: • Prof Phil Hannaford – p.hannaford@abdn.ac.uk • Prof Alison MacLeod – mmd175@abdn.ac.uk • Dr Gail Holland – g.holland@abdn.ac.uk Tel: 01224 - 555076 • Lynda Sime – lynda.sime@nhs.net Tel: 01224 -554656