Transcript Setting Up Clinical Trials

Medicines and Healthcare
products Regulatory Agency
(MHRA)
Statutory Good Clinical Practice
(GCP) Inspection of Cardiff
University
Research Policy & Management
RACD
The plan for today
• The inspectors
• Inspection process
• Inspection Outcomes
• Preparing for the Inspection
• Experience of an inspection
Research Policy & Management
RACD
The Inspectors
GCP Inspectors
GMP Inspectors
Group Manager
Inspections
Offices:
York
Welwyn Garden City
Market Towers
GLP Inspectors
GPvP
Inspectors
Expert
Inspectors
Serious Breach
of GCP
Research Policy & Management
RACD
What does an inspection involve?
http://www.mhra.gov.uk/CON2024532
Research Policy & Management
RACD
Pre-Inspection Dossier
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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:
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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
Research Policy & Management
RACD
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
Research Policy & Management
RACD
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.
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Chief / Principal Investigator
Research teams e.g. Research Fellow, Research Nurse
RACD
Laboratories
IT
Archiving facilities
• Inspection plan can change
Research Policy & Management
RACD
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.
Research Policy & Management
RACD
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
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Training
– Inadequate knowledge of Clinical Trial Regulations
– Lack of GCP training amongst trial team
•
Informed Consent
– No record of consent
– Incorrect version
Research Policy & Management
RACD
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)
Research Policy & Management
RACD
Common Findings
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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
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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
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Filing of essential documents
– Poorly maintained site files
– Poor document control and management
– Forms not signed or not completed correctly
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Laboratory
– No evidence of how equipment is maintained, calibrated and serviced
Research Policy & Management
RACD
University (RACD) Preparations
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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
Research Policy & Management
RACD
How can Research Groups/Units prepare?
• Awareness raising
• Familiarity with legislation, internal and external
guidance
– ICH GCP (Topic E6)
http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf
– University Research Governance web page
http://www.cf.ac.uk/racdv/resgov/index.html
– www.ct-toolkit.ac.uk
• GAP analysis
– Essential documentation / Unit SOPs
– Action plan
Research Policy & Management
RACD
How can Researchers prepare?
• Familiarity with legislation, internal and external
guidance
– ICH GCP (Topic E6)
http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf
– University Research Governance web page
http://www.cf.ac.uk/racdv/resgov/index.html
– www.ct-toolkit.ac.uk
• Essential Documentation - Self-assessment of the trial
using Trial Master File checklist
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Approvals
Document Control
IMP management
Delegation Logs
SOPs
Pharmacovigilance
Equipment
Research Policy & Management
RACD
Summary
• Anyone involved in Clinical Trials
• Co-operation and engagement
• Early Preparation
• Action plan to remedy issues
Research Policy & Management
RACD
Contacts
Research Governance Team
[email protected]
X79277 (01798 79277 from Heath)
Chris Shaw
Matthew Harris
Kathy Pittard Davies
Research Policy & Management
RACD
Medicines and Healthcare
products Regulatory Agency
(MHRA)
Statutory Good Clinical Practice
(GCP) Inspection of Cardiff
University
Research Policy & Management
RACD