Change management for the launch of the new EudraVigilance system

The updated European Union (EU) pharmacovigilance legislation brought about significant changes to electronic reporting requirements for suspected adverse reactions, to support better safety monitoring for medicines and a more efficient system for stakeholders. To support these changes, the European Medicines Agency (EMA) launched the EudraVigilance system with enhanced functionalities on 22 November 2017.

Current requirements

Stakeholder	Requirement
EMA	To enhance EudraVigilance to deliver simplified reporting, better quality data and improved searching, enhanced analysis and tracking functionalities as well as extended access in particular for marketing authorisation holders To make all individual case safety reports (ICSRs) for suspected adverse reactions that occur in the European Economic Area (EEA) available to the World Health Organisation (WHO) Uppsala Monitoring Centre (UMC) in a timely manner
Marketing authorisation holders	To monitor the EudraVigilance data they have access to for safety signals and to report these to EMA and national competent authorities EMA and the European Commission have agreed some transitional arrangements in order to streamline the implementation of this new process. For more information, see signal management
All stakeholders within the European Union (EU) medicines regulatory network	To implement simplified reporting procedure for ICSRs in the EU, with EMA receiving ICSRs from marketing authorisation holders and forwarding the reports to the national competent authorities concerned To report non-serious cases of suspected adverse drug reactions that occur in the EEA to EudraVigilance To use international data standards, including the International Organization for Standardization (ISO)/ICH E2B(R3) data structure for individual case safety reports (ICSRs)

Benefits of the enhanced EudraVigilance system

The enhanced EudraVigilance system has several significant benefits, including:

New feature	Benefit
Enhanced signal-detection and data-analysis tools to support safety monitoring directly by Member States and marketing authorisation holders	Better detection of new or changing safety issues, enabling rapid action to protect public health
Improved quality and completeness of ICSR data	Better searchability and more efficient data analysis
Enhanced scalability of the EudraVigilance system	Able to support an increased number of ICSRs due to the new requirement to report non-serious cases to EudraVigilance
Simplified reporting of ICSRs to EudraVigilance and the rerouting of ICSRs to Member States	Reduced duplication of efforts Marketing authorisation holders no longer have to provide ICSRs to national competent authorities, they have to submit these to EudraVigilance only
EMA provides data to the World Health Organization (WHO) Uppsala Monitoring Centre directly from EudraVigilance	Enhanced collaboration between EMA and WHO Member States no longer need to carry out this task

EudraVigilance stakeholder change management plan

The detailed change management plan provides stakeholders with information on the technical changes EMA is introducing in the EudraVigilance system as well as business process changes required to work with the enhanced system. EMA first published this document in October 2015 and the latest version of the plan in November 2017:

Revised EudraVigilance stakeholder change management plan

This provided a starting point for national competent authorities in the EEA, marketing authorisation holders and sponsors of clinical trials to develop their own internal implementation plans to prepare for the launch of the enhanced EudraVigilance system on 22 November 2017.

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Testing for the enhanced EudraVigilance system

EMA advised organisations that had already established electronic submission of ICSRs to EudraVigilance to perform the gateway configuration and communication testing with XCOMP (refer to the EU ICSR Implementation Guide ) prior to the launch of the enhanced EudraVigilance system on 22 November 2017.

Organisations that are continuing to use established E2B(R2) systems were advised to use the E2B(R3) test files available for download from the external compliance testing environment (XCOMP) and test the upload of the files in their local pharmacovigilance/safety system with a backwards-and-forwards conversion solution.

EMA released the following guidance documents to support testing:

Organisations preparing for electronic transmissions of ICSRs to EudraVigilance for the first time or performing major upgrades to established systems (e.g. submission of ICSRs in ICH E2B R3 format) should perform testing with EMA and consult EudraVigilance: electronic reporting for further information.

EudraVigilance go-live strategy

To enable EMA to release an enhanced Eudravigilance system on 22 November 2017, a downtime period of 10 business days was required. A number of key EudraVigilance functionalities were entirely or partially unavailable from 8 to 21 November 2017. Additional EMA IT systems were also affected during that period.

To facilitate the transition, the EU Regulatory network's pharmacovigilance business team prepared a EudraVigilance go-live plan and a technical note in consultation with the Pharmacovigilance Risk Assessment Committee (PRAC), the Clinical Trials Facilitation Group (CTFG) and the EudraVigilance Expert Working Group.

The plan outlined a set of detailed, sequenced tasks and activities, which were required prior to the enhanced EudraVigilance production system launch, explained the handling of legacy data resulting from the downtime and described the agreed temporary arrangements with each national competent authority.

EudraVigilance go-live plan

The technical note described the IT systems that were affected by the downtime and provided further instructions to competent authorities, applicants, marketing authorisation holders and sponsors of clinical trials.

Technical Note on the planned EudraVigilance downtime from 8 to 21 November 2017

In addition, a Communications plan for EMA and national competent authorities in the EEA described the EMA communication milestones with national competent authorities in the EEA that were part of the new EudraVigilance system go-live strategy. It identified the stakeholders affected, their needs and interests. Each Member State had the possibility to align its own communication strategy with the one prepared by EMA.

Technical and business process changes: questions and answers

The document below addresses questions received from stakeholders in preparation of the launch of the new EudraVigilance system. It summarises questions received through the Agency's service desk and as part of the technical and pharmacovigilance/EudraVigilance support webinars organised by the EMA. The document is regularly updated and should be consulted as a first reference before contacting the Agency's service desk.

Questions and answers on the launch of the EudraVigilance system received from stakeholders (updated 04/12/2018)

The questions and answers below are based on the stakeholder change management plan . They also include detailed documentation on the changes in reporting, downloading and analysis of data.

The main technical change to the EudraVigilance system was the implementation of the new ISO ICSR format for the submission and exchange of ICSRs in line with the applicable ICH E2B(R3) and EU ICSR Implementation Guides.

To incorporate the new format, EMA implemented several other changes in EudraVigilance. These include:

adapting the EudraVigilance Gateway, the secure electronic communication tool to exchange ICSRs, to accept ICH E2B(R2) as well as (R3) files;
adapting the EudraVigilance database management system (EDBMS) to support the storage and processing of reports submitted with the new ICH ICSR format
migrating all existing ICH E2B(R2) ICSR data to the new ICH ICSR format;
redesign of EVWEB, the web application for the electronic reporting and management of ICSRs in the ISO ICSR format, using a new technology;
introducing new functionalities in the EudraVigilance data analysis system (EVDAS), including the adrreports.eu portal, to support analysis of data and support signal management activities.

In addition, EMA added the following two new functionalities to the system:

EudraVigilance rerouting functionality, which defines the rules for the forwarding of ICSRs to the national competent authority (NCA) where the adverse reaction occurred (rules can be set by NCAs according to their needs and preferences);
ICSR download functionality to enable marketing authorisation holders to download ICSRs concerning their products or ICSRs reported with a substance for which they hold a marketing authorisation in the EEA.

The extended EudraVigilance medicinal product dictionary is no longer an integral part of EudraVigilance version 8 but continues to be available as an independent system component.

The implementation of the new EudraVigilance system changed the following business processes:

Marketing authorisation holders no longer provide ICSRs to national competent authorities and submit these to EudraVigilance only.
Following the switch to simplified reporting, EMA submits ICSRs through EudraVigilance to the WHO Uppsala Monitoring Centre, rather than national competent authorities doing this;
Marketing authorisation holders have a legal obligation to monitor the data available in EudraVigilance and inform EMA or national competent authorities of any safety signals identified. EMA granted marketing authorisation holders access to EVDAS to use signal detection, analytical and reporting functions to the extent necessary to fulfil their obligation.

For more in-depth analysis of the changes to each stakeholder group, see:

EudraVigilance stakeholder change management plan .

All impacted organisations should have prepared for the changes in reporting, downloading and analysis of data before the new EudraVigilance system was moved into production.

National competent authorities should have planned communication activities at national level to ensure that marketing authorisation holders in their territory were aware of the changes and had systems in place to comply with their obligation to report directly to EudraVigilance, prior to 22 November 2017.

EMA's communication activities included:

general updates to support stakeholders in preparing for IT and business process changes;
targeted communications when reaching project milestones.

For information on when the next project milestones are expected and the corresponding communication activities planned, see:

Key project milestones and summary of associated communication activities

ICH provides the basis for the implementation of the ISO ICSR standard. Relevant documents are downloadable from the ICH Electronic Standards for the Transfer of Regulatory Information (ESTRI) website. They are also listed below.

To complement the ICH E2B(R3) implementation guides, EMA has developed a specific EU ICSR implementation guide and supporting documents, including user guides and training material. These documents provide additional information on specific EU regional requirements not provided for in the ICH documentation. They are progressively published when finalised.

ICH implementation guidance

Documentation	Description
ICH Implementation guide package	Set of documents including the ICH ICSR implementation guide, backwards and forwards compatibility recommendations and element mapping.
ICH E2B(R3) Questions and answers	Relevant for technical E2B questions.

EU implementation guidance

Documentation	Description
European Union individual case safety report (ICSR) implementation guide	This guidance describes the EU-specific requirements to generate a valid ICSR safety and acknowledgment message in the international format EN ISO ICSR 27953-2:2011 in accordance with ICH E2B(R3) guidance.
EU ICSR implementation guide business rules spreadsheets	These spreadsheets include all the ICH E2B(R3) and EU specific business rules in a format to help system developers.
EU backwards forwards conversion element mapping spreadsheet	This document describes the relationship between EU specific data elements in E2B(R3) and E2B(R2). This document is an addition to the ICH backwards-forwards conversion rules. It covers additional EU-specific rules for the conversion back and forth between E2B(R2) and E2B(R3).
EU BFC conversion v. 2.8	The ICH backwards-forwards conversion tool updated to include additional EU-specific data fields.
EU E2B(R3) code lists	The list of codes for EU-specific data fields.
UCUM units for E2B (R3)	The list of valid UCUM units that can be used in the EU for E2B (R3).
EU reference instances	ICH reference instances amended to include EU-specific data fields.
EU E2B (R3) testing files	Additional example instances to be used for testing E2B(R3) transmissions with the enhanced EudraVigilance system.

Revised EudraVigilance access policy

Documentation	Description
Revised EudraVigilance access policy (current)	The revised EudraVigilance access policy, which governs the level of access different stakeholder groups have to adverse drug reactions reports. The revised version came into force on 22 November 2017.
Overview of comments received on 'Draft revision of EudraVigilance access policy for medicines for human use'	The comments received on the draft revision of the EudraVigilance access policy during its public consultation between 4 August and 15 September 2014.

Good pharmacovigilance practice (GVP) guidance

Documentation	Description
Revised GVP Module VI	This module addresses the management and reporting of adverse reactions to medicinal products.
Revised GVP Module IX	This module describes the general guidance and requirements on structures and processes involved in signal management and how they are applied in the setting of the EU pharmacovigilance and regulatory network.

Guidance documents

Documentation	Description
Note for guidance: EudraVigilance Human – Processing of safety messages and individual case safety reports (ICSRs)	This guidance describes the EU-specific requirements to generate a valid ICSR safety and acknowledgment messages in the ICH E2B(R2) format It should be read in conjunction with the ICH E2B(R2) technical specifications and related materials published on the ICH website
Note for guidance on the Electronic Data Interchange (EDI) of individual case safety reports (ICSRs) and medicinal product reports (MRPs) in pharmacovigilance during the pre- and post-authorisation phase in the European Economic Area (EEA)	The guidance specifies the technical requirements and the process of transmission of electronic reports and messages through the EudraVigilance Gateway established at EMA and describes the obligations that EDI partners have to adhere to in this process to assure a successful electronic communication It also describes the implications of electronic reporting with regard to the legal reporting compliance as defined in pharmacovigilance legislation, the evaluation steps and the recovery procedures in the event of a communication failure
List of pharmaceutical dosage forms	This spreadsheet provides a list of dosage forms used in the EudraVigilance system
E2B(R2) ICSR specification and related files	Technical ICH E2B(R2) ICSR message specification and related files
ICH Harmonised Tripartite Guideline - Maintenance of the ICH Guideline on Clinical Safety Data Management: Data Elements of Transmission of Individual Case Safety Reports E2B(R2)	The document provides details of the data elements for transmission of individual case safety reports by identifying and defining the data elements for the transmission of all types of individual case safety reports, regardless of the source and destination
E2B Implementation Working Group - Questions & Answers (R5)	This document provides questions and answers on the conventions for the harmonised interpretation of the ICH E2B(R2) guideline and messaging specifications

Historical overview of EudraVigilance access policy revisions

Documentation	Description
European Medicines Agency policy on access to EudraVigilance data for medicinal products for human use - Revision 3 (historical)	The revised EudraVigilance access policy, which governs the level of access different stakeholder groups have to adverse drug reactions reports. The revised version came into force on 22 November 2017. This version was superseded by a new revision 4.
Overview of comments received on 'Draft revision of EudraVigilance access policy for medicines for human use	The comments received on the draft revision of the EudraVigilance access policy during its public consultation between 4 August and 15 September 2014.
European Medicines Agency policy on access to EudraVigilance data for medicinal products for human use - Revision 2 (historical)	The revision 2 was adopted by EMA Management Board in December 2015. A minor technical update of Annex B has been carried out and this version was superseded by a new revision 3.
EudraVigilance access policy for medicines for human use - First version (historical)	The EudraVigilance access policy governs the level of access different stakeholder groups have to adverse drug reactions reports.
Explanatory note: EudraVigilance access policy for medicines for human use	The explanatory note on the EudraVigilance access policy for medicines for human use published in July 2011
Overview of comments received on draft EudraVigilance access policy and implemented amendments	The comments received on the draft EudraVigilance access policy during its public consultation and the implemented amendments published in July 2011
Draft EudraVigilance access policy for medicines for human use	The draft EudraVigilance access policy for medicines for human use published in December 2008