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 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. What can you do to prepare?
Handout available with recommendations for addressing key areas of weakness.
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. Common Themes During Interview:
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

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 –
Prof Alison MacLeod –
Dr Gail Holland –
Tel:
Lynda Sime –
Tel: