The Pharmacovigilance Risk
Assessment Committee
GPvP Symposium, 14 March 2014
Dr Julie Williams, PRAC Delegate
Scope of presentation
• Establishing PRAC as public health focussed
• PRAC’s work - use of the new public health protection tools
• Looking ahead – what is still to come
2
Pharmacovigilance legislative
aims
1. Clarity on roles and responsibilities
2. Proactive & proportionate safety monitoring
3. Robust and timely decision-making and consistent
action on safety issues
4. Greater inclusiveness for patients, healthcare
professionals
5. High levels of transparency
6. Best use of resources – avoid duplication
3
Mandate of PRAC
All aspects of the risk management of the use of medicinal products including the detection,
assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to
the therapeutic effect of the medicinal product, the design and evaluation of post-authorisation safety
studies and pharmacovigilance audit
4
Membership of PRAC
Appointed by European
Commission:
Appointed by each
Member State:
1 member + alternate
28 + EEA countries non
voting members
6 members - relevant expertise including clinical pharmacology
and pharmacoepidemiology 1 member/alternate representing
patient organisations 1 member/alternate representing
healthcare professionals
5
HCP and patient representatives
6
PRAC’s public health pillars
Proactive safety
monitoring & planning
Transparency
and
communication
Prompt
benefit risk
action
7
PRAC - Tasks
• RMPs (initial and updates) for all centralised products;
• Signals – identification, prioritisation and evaluation;
• Periodic Safety Updates reports – single assessment;
• Risk minimisation measures and communications;
• Protocols for and results from non-interventional PASS;
• Safety referrals – recommendation to CHMP/CMDh;
- CHMP for referrals involving one CAP, EC final opinion
- CMDh for referrals for NAPs, EC opinion if no consensus
• Other safety related matters at CHMP or member state
request
• EURD and Additional monitoring lists
8
RMP Advice/Assessments
9
Proactive & planned
pharmacovigilance
Major PRAC focus on
signal detection – SMART
(Signal Management
Review Team):
- Tools and processes
- Methodological guidance
- Signal detection methods
Implementing Regulation 520/2012 “the Pharmacovigilance Risk Assessment
Committee shall regularly review the methodology(ies) used and publish
recommendations, as appropriate” [Art 20(3)]
10
Signal Management Process
11
Signal detection
Validation Confirmation Analysis,
prioritization Assessment
Recommendation for action
MAH
MSs
Agency
MSs Agency
PRAC
Signals – summary
Sept 2012 - Dec 2013
• 1 69 for CAPs, 43 for NAPs, 9 for both
• 2 6 referrals ongoing, 2 concluded: restriction of use (codeine) and suspension of MA (HES)
Data source
58 EudraVigilance
35 national review
11 literature
7 FDA/PMDA
5 historical (PhVWP)
6 studies
Outcome
57 labelling changes
17 no regulatory action
8 referral evaluation2
2 update RMP
37 ongoing assessment
Number of signals
1211
12
Monthly review by
PRAC of proposals
for additions to the
list
Communications
campaign starting
1 October 2012
Additional monitoring list
13
PASS Protocols & Results
14
Example of PASS
The applicant should conduct
a 5-year long-term
observational study with
ivacaftor in patients with cystic
fibrosis, including also
microbiological and clinical
endpoints (e.g. exacerbations),
according to a protocol agreed
with the CHMP
http://clinicaltrials.gov/ct2/show/NCT01117012?term=ivacaftor&rank=22
15
Prompt benefit risk
recommendations
• Binding outcomes
from referrals
• Rigorous adherence
to legal timeframes
• PSURs as benefit
risk decision-making
tool
16
PRAC safety referrals
17
18
Urgent Union Procedure 107i
19
Example 107i procedure –
Numeta 13%
• Numeta 13% parenteral nutrition
for preterm babies
• Signal of 14 reports of
hypermagnesaemia – July 2013
• Voluntary recall of Numeta 13%
• PRAC concludes advice
September 2013 to suspend
Numeta 13%, introduce risk
management for Numeta 16%
•
20
Article 31 procedures
21
Article 31 procedures
22
23
“EMA has started a review of
the risks of combining certain
medicines to block separate
stages of the renin-
angiotensin system (RAS) in
the treatment of hypertension
and congestive heart failure”
• 24 substances
• 37 CAPs
• > 16,000 NAPs
• 9 Rapporteurs
• Number of companies
involved unknown
24
Stakeholder involvement
25
PSURs Outcomes
26
Example –Strontium ranelate
Periodic safety update
report identified
increased risk of cardiac
disorders including MI
PRAC advised variation
to restrict MA on safety
grounds
CHMP started referral
under Art 31
27
Transparency
28
Agenda is published on Day 1 of PRAC by mid-day
Meeting highlights are published on Friday of PRAC week
Safety referrals are published on Friday of PRAC week
Signal recommendations are published at the end of the month
Minutes are published on the following month after adoption
Highlights from
2-5 September
PRAC meeting,
published 6th
September
29
Current PRAC priorities
• Increasing stakeholder
involvement
• Strengthening the science base
for benefit risk decision-making
• Optimising use of regulatory
tools for public health
• Measuring the public health
impact of activities
31
Public Hearings
LEGAL BASIS
DEFINITION
OPENESS AND
TRANSPARENCY ORGANISATION
OBJECTIVES WHEN TO HOLD?
• Urgency matter permits
• Extent and seriousness
safety concerns
• Art. 107 and Art. 31
• All info public
• Part of overall assessment
• Declaration of Interests
• Recorded / video streamed
• Language challenge
• Website
• Specific questions
• Priority representatives
of groups / organisations
• Time allocation
• Public invited
• Stakeholders views and
concerns
• Specific questions
• Increased transparency
• Empower EU citizens
• Add value and increase
understanding
• Level of risk acceptance
• Define balance B/R
32
Strengthening the science
base
33
Further legislation…
34
Optimising use of new tools
Referrals –scope,
criteria for triggering
Signal roles and
responsibilities,
methodologies
“EC Joint Action”
35
Joint Action - SCOPE
Strengthening Collaborations to Operate Pharmacovigilance in Europe
Facilitating collaboration among the Member States for the effective operation of the pharmacovigilance system in the EU
36
Public health outcomes
Demonstrably strengthening protection of public health–
what this is all about
37
Summary
• Establishment of PRAC is central to
implementation of EU Pharmacovigilance
legislation
• PRAC’s key focus - delivering the public health
objectives
• Experience demonstrates capability for robust
scientific decision making to rigorous timescales
• Major strides forward in transparency and
stakeholder involvement
38
© Crown copyright 2014
About copyright
All material created by the MHRA, including materials featured within these MHRA presentation
notes and delegate pack, is subject to Crown copyright protection. We control the copyright to our
work (which includes all information, database rights, logos and visual images), under a delegation
of authority from the Controller of Her Majesty’s Stationery Office (HMSO).
The MHRA authorises you to make one free copy, by downloading to printer or to electronic,
magnetic or optical storage media, of these presentations for the purposes of private research,
study and reference. Any other copy or use of Crown copyright materials featured on this site, in any
form or medium is subject to the prior approval of the MHRA.
Further information, including an application form for requests to reproduce our material can be
found at www.mhra.gov.uk/crowncopyright
Material from other organisations
The permission to reproduce Crown copyright protected material does not extend to any material in
this pack which is subject to a separate licence or is the copyright of a third party. Authorisation to
reproduce such material must be obtained from the copyright holders concerned.
40