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

1

2

3

4

5

6

7

8

9

Finding Topic Area

Nature of critical findings by company type – March 2013 to Feb 2014

Generic

Innovative

Critical Findings – previous period

0

1

2

3

4

5

6

7

8

9

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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Proportion of Findings 2013/2014

0

20

40

60

80

100

120

140

160

180

Critical Major Other

Proportion of Findings 2014/2015

0

20

40

60

80

100

120

140

160

180

Critical Major Other

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