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Pharmacovigilance Risk Assessment
Committee (PRAC): Nye tider – nye
opgaver
Doris I. Stenver
Overlæge, medlem af PRAC
Pharmacovigilance Risk Assessment
Committee (PRAC): Nye tider – nye
opgaver
Doris I. Stenver
Overlæge, medlem af PRAC
Overview
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New pharmacovigilance legislation – purpose and
expected achievements
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Pharmacovigilance Risk Assessment Committee – tasks
and responsibilities
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EMA Implementation plan
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GVP modules – status
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Commission Implementing Regulation
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Revision of legislation
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Ancient times…..
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Impact of thalidomide tragedy in the 1960s
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Establishment of drug safety surveillance systems
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Involvement of health professionals
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Decisions based on national experience
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Non-transparent environment
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European Medicines Agency London, since 1995
www.ema.europa.eu
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Present time…..
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Internet era
Transparency
Internationalisation
Competitive power
Innovative power
Disease burden
Involvement of patients
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New pharmacovigilance legislation
 In general, overall strengthening of
pharmacovigilance
 Clear roles and responsibilities
 Rational use of ressources
 Streamlined procedures (administrative and scientific) with
timetables
 New ADR definition
 New PSUR format and scope
 Legal basis for PASS
 Transparency
 HCP & Patient involvement
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Pharmacovigilance – basic steps
Risk detection /
signal detection
Pharmacovigilance audit
Risk assessment
Design and Evaluation of post
authorisation safety studies
Risk and therapeutic effect
assessment
Risk minimisation (regulatory
action) and analysis of impact of risk
minimisation
Communication of risk
and benefit/risk
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PRAC tasks and responsibilities
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Referral procedures for safety reasons
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Signals detected from EU spontaneous reporting systems
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Risk management plans
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PSUR assessments
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Post-Authorisation Safety Studies (PASS)
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Product-related pharmacovigilance inspections
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Safety issues – requested by CHMP or by MS(s)
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Organisational, regulatory and methodological matters
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PRAC agenda September 2012
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Referral procedures for safety reasons: None
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Signals detected: Thirteen
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Risk management plans: One
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PSUR assessments: None
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Post-Authorisation Safety Studies (PASS): None
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Product-related pharmacovigilance inspections: Two
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Safety issues – requested by CHMP or by MS(s): None
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Organisational, regulatory and methodological matters: Many 11
PRAC agenda September 2012 – new signals
4.1.10. Varenicline - CHAMPIX (CAP)
 • Signal of seizures
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Status: for initial discussion
Regulatory details:
 PRAC Rapporteur: Doris Stenver (DK)
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PRAC recommendation flow
PRAC
Coordination
Group CG
CHMP
Recommendations
Member States
European Commission
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PRAC agenda September 2012 – new signals
4.1.8. Somatropin – NUTROPINAQ, OMNITROPE
(CAPs, NAPs)
 • Signal of convulsions (SMQs – Standardised MedDRA
Queries)
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Status: for initial discussion and Rapporteur
appointment
Regulatory details:
 PRAC Rapporteur: to be appointed
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PRAC agenda September 2012 - inspections
8.2. On-going or concluded pharmacovigilance
inspections
 Disclosure of information on results of pharmacovigilance
inspections could undermine the protection of the purpose
of these inspections, investigations and audits. Therefore
such information is not reported in the agenda.
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PSUR Single Assessment – EURD list
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(11.3.3)
EU Reference Date List for > 3.300 products
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Compiled by EMA, based on EVMPD, PSUR WS and Synchronisation
lists
4 consultations with MSs
PRAC consultation September 2012  CHMP & CMD(h) consultation /
agreement September 2012
Publication by 30th September – simultaneously with list on signal
WS; becomes binding in April 2013
Monthly updates – dynamic EURD
Process for maintenance under discussion
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Not all is written in stone!
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Appointment of PRAC Rapporteurs
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Guiding principles – best possible and available expertise,
knowledge continuity, “fresh pair of eyes”
Legacy medicines – open up for PRAC rapporteurships to
all PRAC delegates
New MAAs – PRAC co-Rapporteur from same MS as CHMP
Rapporteur
Gradual phasing in from 4Q2012 in relation to all CAPs
due for PSUR assessments of PASS results evaluation in
1Q2013;
Referrals – only non-CAPs
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Rapporteur: open to all PRAC delegates
Co-Rapporteur: triggering MS
Referrals – mixture of CAPs and non-CAPs
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Rapporteur: PRAC rapporteur for the CAPs
Co-Rapporteur: triggering MS
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EMA Implementation Plan February 2012
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Launched 1 February
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Activities in 2012 and beyond 2012 (budget and ressource
restrictions)
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Activities contributing to public health highest priority, followed by
those increasing transparency and improving communication, and
with lowest priority those that simplify procedures
4 main topic areas
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Collection of key information on medicines
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Better analysis and understanding of data and information
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Regulatory action to safeguard public health
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Communication with stakeholders
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Collection of key information on medicines
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Risk Management Plans (RMPs) (GVP-V)
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Periodic Safety Update reports (PSURs) (GVP-VII)
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Strenghtened procedures for submission; beyond 2012 establishment
of a risk management effectiveness monitoring system
Benefit-Risk evaluation tool; new procedures for submission (CAPs),
list of Union reference dates; beyond 2012 focus on PSURs for NAPs
Post-authorisation safety and efficacy studies (PASS/PAES)
(GVP-VIII)
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Require and enforce PASS/PAES; scientific GL to support delegated
act on criteria for PAES
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Collection of key information on medicines
 Electronic submission of core medicine
information by pharmaceutical industry (art. 57
requirements)
 Extensive requirements – Yes! But in order to conduct
effective SD on data in Eudravigilance a comprehensive
drug dictionary is a basic requirement; revised legal
notice in febr. 2012
 Reporting by patients
 Information to be provided on this new opportunity
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Better analysis and understanding of data and
information
 Eudravigilance and Signal Detection
 Revised SD process for CAPs; improved access to data
on NAPs; improvement of data quality ongoing
 Additional Monitoring
 First list of medicines subject to additional monitoring
 IT systems to support processing and analysis of
data
 Full development of new IT systems will not begin until
after 2012
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Regulatory action to safeguard public health
 Scientific committees and decision-making
 Pharmacovigilance Risk Assessment Committee (PRAC)
inaugural meeting 19 July 2012 (Bruxelles)
 CMD(h) strengthened mandate – will lead on decision-
making based on PRAC recommendations
 Opinion-making power by either consensus or majority
vote  legally binding EC decisions
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Regulatory action to safeguard public health
 Strengthening referral procedures
 Urgent Union Procedure
 Designed to address significant emerging safety
issues with a medicine available in the EU,
regardless of authorisation procedure
 Systematic involvement of PRAC in providing safety
expertice for assessment and to identify appropriate
regulatory actions, for subsequent adoption by CHMP
or CMD(h)
 Increased transparency (publication of information
and public hearings)
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Communication with stakeholders
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Publication of
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Coordination of safety anouncements
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Agendas, minutes, assessments, recommendations and opinions
Scope – PRAC, CMD(h), CHMP
For nationally authorised products
Ensure consistent and coherent safety advice across Europe
Public hearings
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In relation to referrals within the Urgent Union Procedure
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Good Pharmacovigilance Practices (GVP)
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GVP Modules – 1st wave: FINAL June 2012
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I PhV Systems and their Quality Systems
II PhV System Master File
V Risk Management Systems
VI Individual Case Safety Reports
VII Periodic Safety Update Reports
VIII Post-Authorisation Safety Studies
IX Signals
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Good Pharmacovigilance Practices (GVP)
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GVP Modules – 2nd wave: Ongoing
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III Audits Public Consultation until 21 September 2012
IV Inspections Public Consultation closed; time table for finalisation
awaited
X Additional Monitoring Public Consultation closed; time table for
finalisation awaited
XI Public Participation Drafting ongoing
XII Continuous phv, B/R evaluation, communication planning and
decision-making for regulatory action Drafting ongoing
XV Safety Communication Consultation until 21 September 2012
XVI Risk Minimisation Measures Drafting ongoing
XIII Incident management (scope tbc)
XIV International collaboration (scope tbc)
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Good Pharmacovigilance Practices (GVP)
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GVP Considerations for product- and population-specific
pharmacovigilance
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Biological medicinal products incl. biosimilars
Vaccines (Review drafting ongoing)
Pregnancy
Children
Elderly
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Commission Implementing Regulation
(EU) No 520/2012
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I. Pharmacovigilance System Master File
II. Minimum requirements for quality systems
III. Minimum requirements for Eudravigilance database,
details on signal management
IV. Terminology, formats, standards
V. Individual Case Safety Reports
VI. Risk Management Plans
VII. Periodic Safety Update Reports
VIII. Post-Authorisation Safety Studies
IX. Final provisions
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All is written in stone - almost!
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Revision of legislation
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Art. 23 of the Regulation concerning the list of medicinal
products subject to additional monitoring
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Medicinal products where a PASS is a condition for the MA
Medicinal products approved in exceptional circumstances and
subject to specific obligations (art. 14 (7) and (8) REG, art. 22 DIR);
MAH with stricter obligations to register / report suspected ADRs
Strengthened obligations for MAHs to inform regulatory authorities
about causes underlying withdrawals of medicinal products, request
for withdrawal of MA or decision on not to apply for renewal of a MA.
MAH shall in particular declare if such actions are based on any of
the grounds set out in art. 116 and 117(1) of Directive 2001/83
Art. 107i of the Directive, Urgent Union Procedure
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…when urgent action is considered necessary… deleted; Except art.
107i(1), point e (new contraindication, reduction in recommended
dose or a restriction to the indications)
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