MHRA Pharmacovigilance
Inspections: Practical Examples
and Findings 2013/2014
GPvP Symposium, 14 March 2014
Sophie Keddie, GPvP Inspector
The Metrics
March 2013 - February 2014
• 62 Inspections
• 320 Findings
• 15 Critical, 169 Major, 136 Other
Reference Safety Information
40% of the year’s Critical Findings (6/15 findings)
Critical Findings March 2013 - Feb 2014
Reference Safety Information
Signal Management
QMS
MAH Oversight
Non-interventionalProgrammes
System Failure
PSURs
Collection and collation of PVdata
Critical Findings – company type
0
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Finding Topic Area
Nature of critical findings by company type – March 2013 to Feb 2014
Generic
Innovative
Critical Findings – previous period
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System Failure Expedited Reporting Signal Detection Reference SafetyInformation
QPPV
Finding Topic Area
Nature of critical finding by company type - March 2012 to Feb 2013
Generic
Innovative
Common Findings
1. Case Processing
Seriousness Assessments
Death, life-threatening, inpatient hospitalisation or
prolongation of existing hospitalisation, persistent or significant
disability or incapacity, congenital anomaly or birth defect
How performed?
– Important Medical Event list (IME)?
– Company Specific Always serious list?
– Is the assessment conservative?
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Case Processing
Example: Case event classified as “malignant neoplasm”,
assessment provided - “patient had a history of cancer, maybe
it flared up again”. Assessment = Non-serious.
• MAH used an “Always Serious List” and the term was
included.
• Assessment was based on information surrounding the
case not the event itself.
Serious assessment = Independent process to medical
evaluation, causality and validity of the case.
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2. Literature Searching
Marketing authorisation holders are expected to maintain
awareness of possible publications through a systematic
literature review of widely used reference databases no less
frequently than once a week. [GVP VI]
• Comprehensive search terms?
• Brand name, special situations
• Searches on date?
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Literature searching
Example: Weekly MEDLINE searches performed on brand
name, generic name, and a date limit for publication date
used.
• Date of publication = date on which the issue of the
journal was published
• Date completed = date processing of the record ends
MeSH headings have been added, quality assurance
validation, record distributed to PubMed and licensees.
• Not all relevant articles that had been newly distributed on
MEDLINE in the week of the search had been identified.
Articles omitted from the literature review.
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3. Quality Management System
Audit
• Audit universe not defined or comprehensive
– Did not include:
• All PV processes
• PV activities run by affiliated organisations (partners)
• PV activities delegated (distributors)
• PV service providers
• Audit Plans
– Risk based rationale not defined or not appropriate
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4. Signals
Signal management
All validation, prioritisation, assessment, timelines, decisions,
actions, plans, reporting as well as all other key steps should
be recorded and tracked systematically [GVP Module IX]
• No process to track systematically
• The key steps are not tracked e.g. no timelines
• Tracking system not comprehensive
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5. PSMF
Still a Potential Source of Major Findings
• Not produced
• DDPS not maintained where relevant
• PV Processes not described in full
• For example, no description only a reference to SOPs
• Signal detection activities not sufficiently detailed
• PSMF Metrics not complete
• Audits
• Insufficient detail of findings
• Significant findings & CAPA in Annex
• Lists in Annex incomplete
• The listing of products in Annex H does not include the
worldwide marketing status of the products
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6. Non-Interventional Studies &
Patient Support Programmes
• No central repository
• Drug safety - Unaware of what is running where
• Vendor Training
• Not completed - What information to collect and transfer
• Reconciliation not comprehensive
• All safety information collected
• Contracts
• Out of date and incomplete
• PV language relating to transfer of safety reports missing
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7. Contracts & Agreements
• Safety Data Exchange Agreements
– Not in place for all partners
– Language not consistent with legislation
• Special situations?
• Invalid cases?
• Reconciliation
– No checks to ensure all safety information transferred
from partners or distributors
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Conclusions
How to be compliant?
• RSI – Still the main reason for Critical Findings
• Communications PV and Regulatory Affairs
• Timely procedures
• Get up to date with the legislative requirements
• Signal tracking
• QMS
• PSMF
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