MHRA powerpoint template - TOPRA

TOPRA Annual Symposium
From Risk Management to
Benefit Risk Management
Regulatory challenges
following the strengthened EU
Pharmacovigilance Legislation
Dr June Raine
Medicines and Healthcare products
Regulatory Agency
5 October 2010
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Agenda/Objectives
• What is context for the new European
pharmacovigilance legislation?
• What are key regulatory challenges
following strengthened EU legislation ?
• How to move from risk management to
benefit risk management?
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Context for the new EU
Pharmacovigilance legislation
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The problem…
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Historical perspective
A European Commission
review in 2004 found……
• Unclear roles and
responsibilities
• Complex ADR reporting rules
• Differences at member state
level
• Complex decision making
procedures
• Lack of robust safety studies
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Goals of EU Pharmacovigilance
legislative revision
Strengthening and rationalizing
the community pharmacovigilance
system, with overall objectives of:
• Better protection of public
health
• Ensuring proper functioning of
the internal European market
• Simplification of current rules
and procedures
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Where are we now?
• Final text for legislation agreed by
Parliament and Council on 23 June 2010
• Final voting at European Parliament
22nd September 2010
• Publication expected Q1 2011.
- 18 additional months for transposition
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Commission, Council, Parliament
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"Enhancing our capacity to detect and collect
adverse drug reactions across the EU, as well as
better coordination with national authorities and
pharmaceutical companies, is a key step towards
making sure risks related to the use of medicinal
products are highlighted in a timely manner and duly
assessed…
“More transparent communication about
pharmacovigilance activities, together with a more
efficient overall system at EU level, will enhance
patients' trust in the medicines they are taking, as
well as in the authorities that guarantee their safety",
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Key regulatory challenges
following new EU legislation
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Key regulatory challenges
•New committee set up
•Signal detection
•Worksharing of PSURs
•Decision-making processes
•Transparency
•Post authorisation efficacy studies
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PV Risk Assessment Committee
Mandate – key role
initial analysis of signals
PSURs and PASS,
agreement of risk
management systems
pharmacovigilance risk
assessments
therapeutic context
Status of PRAC advice
Recommendations to CHMP
and CMDh to be respected, if
not explanation to be given
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Signal detection
• Wider scope of AR definition:
implications for collection and
database management
• MAH reports direct to
Eudravigilance when meets
functional specifications
• Electronic reporting via
standard form
• Patient reporting
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Eudravigilance signal function
•Direct evidence that >54%
serious safety issues can be
detected earlier if Eudravigilance
used in addition to other
pharmacovigilance resources
•Analysis of pooled data
Detection of rare ADRs
Earlier as absolute
numbers are greater
Drug Safety 33(6) 475-487
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Additional monitoring
• New active substances
• New authorisations of biological
products (including biosimilars)
• Plus any other, on request of
NCAs (+PRAC) for products with
specific requirements in RMP
▼
• Specific symbol and text in SPC,
PIL
• 5 years or once conditions met,
whichever last
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Worksharing of PSURs
• PSUR (routine) waivers: generics, herbals, but not
for hybrids and informed consent
• No waiver if justified by NCAs +PRAC:
- PhV concern, innovator out of the market.
• Assessment report to be adopted by CHMP or CG
only in case of proposed changes to MA conditions
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Current PSUR worksharing
Allocated P-RMS for PSUR Work-Sharing
80
70
69
60
50
40
30
20
10
0
56
50
47
41
34
31
25
26
22
20
18 17
16 17
12
12
7
7
4 4
3
1
1
AT BE BG CY CZ DE DK EE EL ES FI FR GR HU IE IS IT LI LT LU LV MT NL NO PL PT RO SE SI SK UK
Member State
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Decision-making procedures
• Two procedures as result of PhVig
data, depending on urgency:
- Article 31
- Article 107i (urgent procedure)
• To be applied to all products (inc
centrally authorised) when
authorised in more than 1 MS
• Possibility of public hearings:
general principles, PRAC decides,
future EMA guidelines.
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Transparency & Communication
• EMA to set up and maintain
European medicines web portal
• Summary of committee meetings
regarding PhVig activities
• Risk management plans
• List of medicines under
additional monitoring
• Initiation of safety procedures
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Post authorisation efficacy
studies
• Duly justified requirement from
competent authorities
• At the time of the granting of MA or
later, different scenarios:
- Data that can only be obtained
after MA grant
- Scientific/methodological advances
• Further elaboration on different
situations where PAES required
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Moving from risk management
to benefit risk management
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Regulatory evolution
3. Proactive benefit risk
management, throughout
product life cycle
1. Risk detection
Individual case reports
2. Risk management
–pharmacovigilance plans,
risk minimisation
1980s 2005 2010
22
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Moving from RMP to BRMP
• What have we learnt so far?
- experience with PASS and RMPs
- advanced therapy medicines
• Updating RMP Guidelines
• New methodologies, research capacity
• International perspectives
• Communication challenges
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Example - sibutramine
NEJM,
2010,
Sept 2
James
et al
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Experience with RMPs
Giezen et al 2009
Drug Safety 32(12) 1175
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Updating of RMP Guideline
• Modular approach
• Incorporate efficacy
guidance
• Active substance based
• Draft by end 2010
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B:R management - challenges
• Access to robust evidence on
emerging risk in post authorisation
phase
• Good data on how medicine is
being used in practice
• Good data on background rates in
exposed population
• Time dimension – evolving
evidence throughout life cycle
• Benefit risk not (well) quantified at
time of authorisation
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Innovative Medicines Initiative
Public Private Partnership
PROTECT Pharmepi
Research on Outcomes
of Therapeutics by EU
ConsorTium
Work packages looking at
innovative methods,
including integration of
data on benefit risk and
graphical representation
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• ENCePP = European Network of
centres for Pharmacovigilance and
Pharmacoepidemiology
• Aim is to facilitate conduct of highquality,
multi-centre, independent
post-authorisation studies
focussing on safety and benefit:risk
• 90 centres, plus specialist networks
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The benefits of ENCePP will be:
• To identify, characterise and
promote access to PhVig /
PhEpi resources in Europe
• Improve research standards
• “ENCePP seal”
• Increase independence and
transparency in research
• Stimulate collaboration and
exchange of information and
experience
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International perspectives
“There is no defined and tested algorithm or
summary metric that combines benefit and risk and
that might permit straightforward quantitative
comparisons of different treatment options which in
turn might aid in decision making”
CIOMS Working Group IV
“Benefit - Risk
Balance for
Marketed Drugs:
Evaluating
Safety Signals”
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CIOMS Working Group IX
On practical considerations for development and
application of a toolkit for medicinal product risk
management
“CIOMS IX plans to develop a pragmatic consensus
guideline to be used by industry and regulators …
A harmonised list of tools for managing risks of
medicinal products which can be applied globally, as
well as potential application of these tools”
April 2010
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B:R communication challenges
• Better ways of expressing benefit risk
• Greater lay and patient involvement in processes
• Public education on benefit risk
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Active communication of benefit risk
PRESS RELEASE
CHMP concluded that the
benefits of Thalidomide
outweigh its risks for treatment
of multiple myeloma….
Clinical studies have shown that
adding Thalidomide can prolong
survival time by about 18 months
in newly-diagnosed multiple
myeloma patients over 65 years
of age as compared to patients….
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Summary
• New EU Pharmacovigilance legislation
will strengthen and simplify systems –
sound rationale and public health goal
• New legislation creates challenges,
opportunity to move to benefit risk
management
• Better methodologies and tools are
needed, and better public
communication of benefit risk is key to
moving forward
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