EudraVigilance: are you ready for change?

Pharmacovigilance Platform Nederland 26 September 2017

Anja van Haren

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Content

1.Introduction

2.MAH obligation for signal detection on EV

3.ADR reports

4.Closure

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Regulation (EU) 1235/2010

Directive 2010/84/EU

EC Implementing Regulation 520/2012

GVP Modules

(Good Pharmacovigilance Practice)

applicable

since July 2012

Pharmacovigilance legislation

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Changes

Risk management plan

Post Authorisation Safety Studies

PSURs

Meten effecten risk minimisation Bijwerkingen

Signaal detectie

Wetenschappelijke committees /PRAC

Transparantie

Farmacovigilantie master file

Farmacovigilantie inspecties

Referrals union procedures

Additional monitoring

Renewal

Webportals

Worksharing

Literatuur monitoring

Art57 database

ISO IDMP

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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

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Transitional Period

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Dec 2010

Jul 2012

Dec 2013

Feb 2017

22 May 2017

22 Nov 2017

publication of

PhV legislation

EV functional specs agreed

EMA MB announcement

on EV full functionality

most of PhV legislation

applies

independent audit of new EV system

new rules will apply:

end of transitional

period

Content

1.Introduction

2.MAH obligations for signal detection on EV

3.ADR reports

4.Closure

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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)

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Access to EudraVigilance

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ICSRs in XML format ICSR forms

e-RMRs ICSR line listings ICSR forms

Access to EudraVigilance

> 6 million ICSRs in EV Post Marketing Module

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Example e-RMR on EMA website

risk-based: at least every 6 months

more frequent for active substances contained in

products under additional monitoring

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

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000587.jsp&mid=WC0b01ac0580727d1b

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Signal management pilot

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

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Content

1.Introduction

2.MAH obligations for signal detection on EV

3.ADR reports

4.Closure

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NCA..1

NCA..2

NCA..28

domestic Non-EU

MAH

domestic

domestic

Old

domestic

domestic

1. Simplified ADR routing

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NCA..1

NCA..2

NCA..28

MAH

domestic

all

domestic

domestic

ADRs on own

substance

New

1. Simplified ADR routing

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EEA

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

2. Non-serious cases

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22 Nov

2017

Receipt of ADR

Day 0

Submission

Day 90

Feb

2018

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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

3. Use internationally agreed standards

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Different XML message

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E2B(R3) E2B(R2)

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– 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

Examples of changes in R3 (1)

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- 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

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Examples of changes in R3 (2)

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variety of possibilities to indicate that information is not available:

Not all null flavours are available for every element

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New: use of Null flavours

NI = no information MSK = information available but withheld UNK = unknown NA = not applicable ASKU = requested but not provided (by reporter) NASK = not asked

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Values allowed for ‘age category’

R2 R3

1 = Neonate

2 = Infant

3 = Child

4 = Adolescent

5 = Adult

6 = Elderly

0 = Foetus

1 = Neonate

2 = Infant

3 = Child

4 = Adolescent

5 = Adult

6 = Elderly

Example of a new value

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

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‘ICSR’ form

replaces

old ‘CIOMS’ form

http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2017/0

6/WC500229803.pdf

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ICSR form

will only appear when data is submitted for that data element

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Content

1.Introduction

2.MAH obligations for signaldetection on EV

3.ADR reports

4.Closure

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Clinical Trial Regulation

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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_content_000629.jsp&mid=WC0b01ac05808768df

Revised GVP Modules

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Applicable from 22nd November: GVP Module VI Revision 2 (published July 2017) GVP Module IX Revision 1 to be published Oct 2017

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EMA training

EV page: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000679.jsp&mid=WC0b01ac05800250b5

EV training page: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000162.jsp

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

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Thank you for your attention

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• 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

Abbreviations

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