EudraVigilance: are you ready for change? Pharmacovigilance Platform Nederland 26 September 2017 Anja van Haren 1
Content 1. Introduction 2. MAH obligation for signal detection on EV 3. ADR reports 4. Closure 2
Pharmacovigilance legislation Regulation (EU) 1235/2010 applicable since July 2012 Directive 2010/84/EU EC Implementing Regulation 520/2012 GVP Modules (Good Pharmacovigilance Practice) 3
Changes Risk management plan Literatuur monitoring Referrals union procedures PSURs Art57 database Additional monitoring Post Authorisation Safety Studies Renewal ISO IDMP Meten effecten risk minimisation Bijwerkingen Webportals Wetenschappelijke committees /PRAC Farmacovigilantie master file Farmacovigilantie inspecties Transparantie 4 Signaal detectie Worksharing
Transitional Provisions Legal provisions for a transitional period for some of the new requirements: These could only enter into force after a major upgrade of EV Signal detection: - Obligation on MAHs to monitor EV ADR reporting: - Simplified logistics for ADR reporting - Submission of non-serious ADRs from EEA - Use of internationally agreed standards for exchange of information 5
Transitional Period publication of PhV legislation EV functional specs agreed EMA MB announcement on EV full functionality Dec 2010 Jul 2012 Dec 2013 Feb 2017 22 May 2017 22 Nov 2017 most of PhV legislation applies independent audit of new EV system new rules will apply: end of transitional period 6
Content 1. Introduction 2. MAH obligations for signal detection on EV 3. ADR reports 4. Closure 7
Signal detection & management Implementing Regulation, Art 18 & 21: obligation on MAHs to monitor EV to the extent that they have access to the database - with a frequency proportionate to the identified risk, the potential risks and the need for additional information MAH shall validate new signals and forthwith inform EMA and NCAs Guidance will be provided in Revised Good Vigilance Practice Module IX Signal Management (expected in Oct 2017) 8
Access to EudraVigilance 9
Access to EudraVigilance ICSRs in XML format ICSR forms e-rmrs ICSR line listings ICSR forms > 6 million ICSRs in EV Post Marketing Module 10
Example e-rmr on EMA website risk-based: at least every 6 months more frequent for active substances contained in products under additional monitoring 11
How to inform authorities?* Safety variation: - 3 months (important risks) - 6 months (non-important risks) PSUR (EURD list): - 6 months Standalone signal notification: - 30 days to EMA/NCAs Emerging Safety Issue: -3 working days to EMA/NCAs 12 * Pending finalisation of GVP IX
Signal management pilot http://www.ema.europa.eu/e ma/index.jsp?curl=pages/reg ulation/general/general_conte nt_000587.jsp&mid=wc0b01 ac0580727d1b 13
Signal management pilot Requirement for MAHs to monitor EV data and inform EMA/NCAs of validated signals: will start on 22 February 2018 will only apply, for a pilot period of 1 year, to active substances on additional monitoring list Concerned MAHs have 3 months to familiarise themselves with the EV tools and the new process outlined in GVP IX For other substances, MAHs will still have EV access and will be able to use the data as an additional data source for their existing signal management activities 14
Content 1. Introduction 2. MAH obligations for signal detection on EV 3. ADR reports 4. Closure 15
1. Simplified ADR routing Old Non-EU MAH domestic domestic domestic domestic domestic NCA..1 NCA..2 16 NCA..28
1. Simplified ADR routing New ADRs on own substance all MAH domestic NCA..1 EEA domestic domestic NCA..2 NCA..28 17
2. Non-serious cases Current situation: no obligation to submit non-serious reports to EV From 22 Nov 2017: NCAs and MAHs should submit non-serious EEA cases to EV within 90 days 22 Nov 2017 Feb 2018 Receipt of ADR Day 0 Submission Day 90 18
3. Use internationally agreed standards Since Nov 2005 ADRs are exchanged electronically using an ICH XML message standard: ICH E2B(R2) EU legislation requires use of an ISO standard ISO ICSR 27953-2 -ICH issued an implementation guide for using this ISO standard, referred to as ICH E2B(R3) IT systems are now changing to support E2B(R3), but. this is not just an IT change! is also a major business change 19
Different XML message E2B(R2) E2B(R3) 20
Examples of changes in R3 (1) New data-elements Data elements have become repeatable (e.g. indication) Use of new values for some data elements Option to send attachments (publication, pictures, ECG) New concept of amendment report Flag to indicate which drug was involved in medication error, overdose, misuse, etc 21
Examples of changes in R3 (2) - Use of different languages - Information at case level in R2 has moved to event level in R3: Seriousness criteria Medical confirmation Country where the event occurred 22
New: use of Null flavours variety of possibilities to indicate that information is not available: NI = no information MSK = information available but withheld UNK = unknown NA = not applicable ASKU = requested but not provided (by reporter) NASK = not asked Not all null flavours are available for every element 23
Example of a new value Values allowed for age category 1 = Neonate 2 = Infant 3 = Child 4 = Adolescent 5 = Adult 6 = Elderly R2 0 = Foetus 1 = Neonate 2 = Infant 3 = Child 4 = Adolescent 5 = Adult 6 = Elderly R3 24
Business impact Data entry, assessment as well as analysis! No stop date yet for using R2 messages => R2 and R3 will be used in parallel for now When analysing data, be aware: - that database will contain cases submitted under R2 and R3 (e.g. filtering on new value of foetus introduced in R3 will not retrieve any case reported under R2) - impact of conversions on data quality 25
ICSR form replaces old CIOMS form http://www.ema.europa.eu/docs/e n_gb/document_library/regulatory _and_procedural_guideline/2017/0 6/WC500229803.pdf 26
ICSR form will only appear when data is submitted for that data element 27
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Content 1. Introduction 2. MAH obligations for signaldetection on EV 3. ADR reports 4. Closure 29
Clinical Trial Regulation In principle no changes to SUSAR reporting process until the application of the Clinical Trial Regulation - 1 change: E2B(R3) format can be used for SUSARs Timing depends on confirmation of full functionality of the EU clinical trial portal and database through an independent audit Expected during 2019 instead of October 2018, as previously scheduled http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_cont ent_000629.jsp&mid=wc0b01ac05808768df 30
Revised GVP Modules Applicable from 22 nd November: GVP Module VI Revision 2 (published July 2017) GVP Module IX Revision 1 to be published Oct 2017 31
EMA training EV page: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regul ation/general/general_content_000679.jsp&mid=wc0b01ac 05800250b5 EV training page: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regul ation/q_and_a/q_and_a_detail_000162.jsp 32
To conclude Big changes ahead of us by November 2017 - uncertain what workload/impact will be EV changes impact all stakeholders We need to get familiar with new systems and adapt business processes Training/guidance already available and more coming 33
Thank you for your attention 34
Abbreviations ADR = Adverse Drug Reaction EEA = European Economic Area EMA = European Medicines Agency EV = EudraVigilance E-RMR = Electronic Reaction Monitoring Report EVDAS = Eudravigilance Data Analysis System GVP = Good Vigilance Practice ICH = intenational Council on Harmonisation ICSR = Individual Case Safety Report IDMP = Identification of Medicinal Products MAH = Marketing Authorisation Holder NCA = National Competent Authority PSUR = Periodic Safety Update Report RMP = Risk Management Plan WHO= World Health Organisation 35