1. Medicines and Healthcare products Regulatory Agency (MHRA) Statutory Good Clinical Practice (GCP) Inspection of Cardiff University

2. Preparing for the Inspection Experience of an inspection
The plan for today
The inspectors
Inspection process
Inspection Outcomes
Preparing for the Inspection
Experience of an inspection

3. Group Manager Inspections
The Inspectors
GCP Inspectors
Offices:
York
Welwyn Garden City
Market Towers
GMP Inspectors
Group Manager Inspections
GLP Inspectors
GPvP Inspectors
Expert Inspectors
Serious Breach of GCP

4. What does an inspection involve?

5. Pre-Inspection Dossier
Complete list of Clinical Trials (from May 2005)
Organisational charts
Overview of all facilities
Description of archiving arrangements
SOP index
Detailed procedures in relation to:
Trial management
Quality control and assurance
Computerised systems
Equipment maintenance
Supply of Investigation Medicinal Product
Laboratory procedures
Activities carried out by CU or contracted out by CU

6. Clinical Trial Activities
Any activity involved in the running of Clinical trials at our institution
Archiving
SOPs
Statistics
Adverse Event reporting
Contracts
Data Management
Drug Management
Trial reporting
Project Management
Training
Laboratory
Randomisation
Computer Systems
Regulatory approvals
Study Monitoring
Trial Files

7. What happens during the visit?
1 week inspection by at least 2 GCP Inspectors
Documentation review
University/School/Unit SOPs
Facility Visits
Inspection of several clinical trials to test systems
Interviews with key personnel, e.g.
Chief / Principal Investigator
Research teams e.g. Research Fellow, Research Nurse
RACD
Laboratories IT
Archiving facilities
Inspection plan can change
So what is likely to happen during the visit?
We would expect at least 2 GCP inspectors to be on site.
They may wish to see a tour of some of the facilities e.g. the CRF, pharmacy, laboratories etc.
They may ask to see additional documentation not submitted as part of the Pre-Inspection Dossier – for example other policies or SOPs . As you can imagine, we had to be selective as to what we included in one lever arch file.
They will want to inspect several clinical trials to test systems. These could be studies which are ongoing or studies that have closed since May If they decide they are particularly interested in close down or archiving systems they may well choose a study that has closed.
Who will they wish to interview? Well of course we can’t be certain but from past experience, for the chosen trials they will usually interview the Chief/Principal Investigator and other key members of the same research team. They usually interview these individuals separately.
We expect they will interview key individuals in the R&D Office and probably key individuals in Pharmacy, the laboratories, medical records, IT, radiology.
As this is a statutory inspection, individuals are expected to make themselves available. As there is usually 4-6 weeks notice, clinicians would be expected to make alternative arrangements for clinics, ward rounds etc. The R&D office will of course do everything it can to try and schedule the timetable of interviews to suit both the MHRA AND staff here at the Trust. Once we know which studies are to be inspected in detail, we will ask for a named contact in the trial team to liaise with the R&D office over the logistics of the Inspection as we will be expected to provide suitable rooms for interview, access to office space and access to photocopiers etc.
A member of the R&D Office will attend each interview as notes must be taken.

8. Inspection outcomes 3 categories of findings: Critical: evidence that
i) the safety, well-being or confidentiality of trial subjects have been or have potential to be jeopardised,
ii) the clinical trial data are unreliable
iii) there are a number of Major non-compliances, indicating a systematic quality assurance failure.
insufficient or untimely corrective action regarding previously reported Major non-compliances
Major:
significant and unjustified departure from legislative requirements that may develop into a critical issue unless addressed,
a number of departures from legislative requirements and/or established GCP guidelines, indicating a systematic quality assurance failure.
Other:
departure from legislative requirements and/or established GCP guidelines, but it is neither Critical nor Major.

9. Response to Findings Organisation must respond within 30 days
Critical Findings or a number of Major Findings may lead to suspension of one or all CTIMPs in the organisation
Organisation response
Analysis of findings
Corrective Action
Preventative Action
Plans of assessing effectiveness of preventative action
Timelines
Disputed findings

10. Common Findings Contract & Agreement Preparation
Lack of written agreements with collaborators
Inconsistencies between protocol and contract
Delegation of duties without agreements/systems in place
Lack of identification of CI and all trial team at outset
Quality System
Lack of SOPs
Insufficient time between issuing and implementing SOPs, leading to training issues
Team meetings not documented
Training
Inadequate knowledge of Clinical Trial Regulations
Lack of GCP training amongst trial team
Informed Consent
No record of consent
Incorrect version

11. Common Findings Investigational Medicinal Product (IMP) management
Inadequate provisions for storage of IMPs
Insufficient records for the chain of custody
Inadequate procedures for QP release
Lack of documentation confirming role of Pharmacy/CI
Pharmacovigilance
Inadequate Pharmacovigilance systems and/or inadequate use of systems in place
Lack of awareness of legislative requirements
Standardisation or arrangements for un-blinding SAEs arising from blinded trials
Annual safety report to MHRA not made
Data management
Security of trial documents/data
Inadequate retention period
Lack of clarity of data entry and data query processes (Source Data Verification)

12. Common Findings Information Management
Lack of assurance that systems are fit for purpose
Lack of evidence of system security
No clarity on arrangements for backing up data
Regulatory Affairs (e. g. Clinical Trial Authorisations)
Remarks on MHRA approval letters not followed up
Unclear indemnity arrangements
Unclear sponsorship arrangements for DDX studies
Annual and end of study reports not sent
Filing of essential documents
Poorly maintained site files
Poor document control and management
Forms not signed or not completed correctly
Laboratory
No evidence of how equipment is maintained, calibrated and serviced

13. University (RACD) Preparations
Pre-Inspection Dossier
Awareness Raising
Delegation of duties
Review of Clinical Trial list
Clinical Trial Monitoring Visits - essential documentation
MHRA Inspection working group
Risk Assessment/GAP analysis – based on common findings from previous MHRA inspections
Individualised preparation plans

14. How can Research Groups/Units prepare?
Awareness raising
Familiarity with legislation, internal and external guidance
ICH GCP (Topic E6)
University Research Governance web page
GAP analysis
Essential documentation / Unit SOPs
Action plan

15. How can Researchers prepare?
Familiarity with legislation, internal and external guidance
ICH GCP (Topic E6)
University Research Governance web page
Essential Documentation - Self-assessment of the trial using Trial Master File checklist
Approvals
Document Control
IMP management
Delegation Logs
SOPs
Pharmacovigilance
Equipment

16. Summary Anyone involved in Clinical Trials Co-operation and engagement
Early Preparation
Action plan to remedy issues

17. Contacts Research Governance Team resgov@cardiff.ac.uk
X79277 ( from Heath)
Chris Shaw
Matthew Harris
Kathy Pittard Davies

18. Medicines and Healthcare products Regulatory Agency (MHRA) Statutory Good Clinical Practice (GCP) Inspection of Cardiff University