EudraVigilance system overview
EudraVigilance is a system for monitoring the safety of medicines. Its components facilitate electronic reporting of suspected adverse reactions related to medicines and the effective analysis of data. This enables the early detection of potential safety issues.
The system contains different components that perform specific tasks in the process of electronic reporting of suspected adverse drug reactions.
This illustration shows how the system components are connected (click to enlarge):
Click on the links below for explanations of each system component:
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The EudraVigilance gateway supports the electronic data interchange (EDI) process, which is based on the secure electronic exchange of safety messages between a sender and a receiver. The safety messages contain individual case safety reports (ICSRs).
An acknowledgement message confirms the receipt and outcome of the validation of a safety message and completes the EDI process.
This gateway process follows the ICH M2 Gateway Recommendation for the Electronic Transfer of Regulatory Information (ESTRI-Gateway).
It ensures the protection of safety and acknowledgement messages against the risk of:
- unauthorised access;
- disclosure;
- alteration;
- delay;
- destruction;
- loss.
The gateway allows for:
- confidentiality;
- verification of integrity;
- non-repudiation of origin and receipt.
Companies and sponsors are responsible for installing and operating software that is suitable for the successful transmission of encrypted and digitally signed safety and acknowledgement messages. Alternatively, they can use service providers for this purpose.
Technical details are provided in the
EU Individual Case Safety Report (ICSR) Implementation Guide
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The EudraVigilance web application (EVWEB) is the interface to the EudraVigilance database management system (EDBMS) and allows registered users to create, send and view ICSRs, safety and acknowledgement messages. EVWEB also enables users to perform queries.
National competent authority (NCA) ICSR rerouting
This EVWEB functionality provides for the automatic forwarding of ICSRs to the applicable national competent authority (NCA) in a member state of the European Economic Area (EEA). It has been available since 22 November 2017.
These ICSRs are initially reported by marketing authorisation holders (MAHs) to EudraVigilance. The rerouting rules are defined in the
EU Individual Case Safety Report (ICSR) Implementation Guide
and can be further customised by NCAs, if required.ICSR download for MAHs
This EVWEB functionality allows marketing authorisation holders to download (export) ICSRs from EudraVigilance for active substances contained in medicinal products for which they hold a marketing authorisation in the EEA.
Following the switch to simplified reporting on 22 November 2017, marketing authorisation holders no longer receive ICSRs directly from NCAs. The 'ICSR download for marketing authorisation holders' functionality allows marketing authorisation holders to access the individual cases in accordance with the EudraVigilance access policy.
The ICSRs can be downloaded in the format described in the ICH E2B(R3) Implementation Guide and corresponding ISO ICSR standard.
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Related EU legislation
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The EudraVigilance database management system (EDBMS) supports the processing and administration of safety and acknowledgement messages and ICSRs. It includes:
- EudraVigilance post-authorisation module (EVPM) dedicated to the collection of ICSRs related to all medicinal products authorised in the EEA. The following ICSR types are collected in EVPM:
- 'spontaneous report';
- 'report from study' with study type 'individual patient use' and 'other studies';
- 'other';
- 'not available to sender' (unknown).
- EudraVigilance clinical trial module (EVCTM) dedicated to the collection of ICSRs of suspected unexpected serious adverse reactions (SUSARs). The following ICSR types are collected in EVCTM:
- 'report from study” with study type 'clinical trials'.
Based on a process that routinely extracts, transforms and loads data (ETL process), the EDBMS is the data source for the EudraVigilance data analysis system (EVDAS).
Related EU legislation
Post-authorisation
- EudraVigilance post-authorisation module (EVPM) dedicated to the collection of ICSRs related to all medicinal products authorised in the EEA. The following ICSR types are collected in EVPM:
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The Agency can use this functionality to automatically or manually code medicinal product information reported in ICSRs.
The reference is the extended EudraVigilance medicinal product dictionary (XEVMPD, also known as Article 57 database), which also supports data submissions on medicines.
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This functionality allows the Agency to detect and manage duplicates in EudraVigilance.
Related documents
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Guideline on good pharmacovigilance practices (GVP) Module VI – Management and reporting of adverse reactions to medicinal products
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Guideline on detection and management of duplicate individual cases and Individual Case Safety Reports (ICSRs)
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The EudraVigilance data analysis system (EVDAS) supports EU pharmacovigilance safety monitoring activities with the main focus on signal detection and evaluation of ICSRs.
EVDAS includes a measure of disproportionality, which is the reporting odds ratio (ROR). EVDAS outputs in relation to pharmacovigilance include:
- electronic reaction monitoring reports (eRMRs);
- line listings of individual cases of suspected adverse reactions;
- individual case report forms.
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The European database of suspected adverse drug reaction reports Adrreports.eu is a publicly accessible portal designed to search and view EudraVigilance data on suspected adverse reactions for authorised medicinal products in the EEA. It also provides general information to aid the understanding of the reports.
Users can search for reports or browse by name of the active substance. For centrally authorised medicines, the product name can also be used.
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The medical dictionary for regulatory activities (MedDRA) is designed to be used in the registration, documentation and safety monitoring of products during the marketing authorisation process. Developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) (multidisciplinary topic M1), MedDRA contains highly specific, standardised medical terminology.
The dictionary is vital to ensure consistency. Its use is a regulatory requirement. MedDRA is maintained by a maintenance and support service organisation (MSSO), which keeps supporting documentation up to date with each release of MedDRA, including MedDRA training materials.
This standardisation eliminates the need for conversion from one terminology to another, thus preventing distortion of data. It guarantees consistency through the different stages of development, which facilitates effective cross-referencing.
MedDRA is used by regulatory authorities, pharmaceutical companies and clinical research organisations worldwide, and its use is a regulatory requirement of marketing-authorisation holders and applicants in the EU.
Update: The MSSO provides updates on the inclusion of COVID-19-related terms and revisions in MedDRA for marketing authorisation holders and national competent authorities on its website:
SubscriptionsFull details of subscription types, rates and processes can be found on the MedDRA website. Micro- and small-sized enterprises are eligible for a MedDRA fee waiver provided they:
- are registered as micro- or small-sized enterprises with EMA;
- are located in the EEA;
- use EVWEB to report to the EudraVigilance clinical trial module and the EudraVigilance post-authorisation module.
The MedDRA fee exemption is applied at the time of EudraVigilance registration.
Sponsors of non-commercial clinical trials may also apply for a fee waiver. The conditions to qualify as non-commercial sponsor are listed in the section 'Electronic data interchange partners' under 'EudraVigilance': how to register.
Points to consider documents
The MedDRA website features ICH-endorsed guides known as points to consider documents. These are companions to the terminology and are updated in line with MedDRA changes.
They are developed and maintained by a working group consisting of regulatory and industry representatives of the EU, Japan and the United States, as well as representatives from Canada, the MSSO and Japanese Maintenance Organisation.
Version control
A newly released version of MedDRA should become the reporting version on the first Monday of the second month after it is released. To synchronise this event over the three ICH regions, the MSSO recommends midnight GMT Sunday to Monday for the switchover. All stakeholders need to adhere to this consistently, to avoid disruption to the electronic exchange of ICSRs.
MedDRA subscribers who are able to quickly update and validate their systems with each release of MedDRA should recognise that, if they submit ICSRs using the updated MedDRA version to a receiving party that has not yet switched, the transmitted ICSRs may be rejected.
Related documents
Related EU legislation
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The EudraVigilance Expert Working Group has coordinated the development of a
list of important medical event (IME) terms
, together with the criteria to facilitate its maintenance.The IME list is maintained twice per year, in line with the releases of new MedDRA versions. EMA publishes new versions of the IME list based on the following schedule:
- Version X.0: by 31st March;
- Version X.1: by 31st of September.
The IME list aims to facilitate the classification of suspected adverse reactions as well as aggregated data analysis and case assessment for the day-to-day pharmacovigilance activities of stakeholders in the EU. The list is for guidance purposes only. Please kindly submit any comments on the IME list to the Agency via web form here.
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The extended EudraVigilance medicinal product dictionary (XEVMPD, also known as the Article 57 database) contains information on authorised medicines for human use and investigational medicines that are or have been studied in clinical trials approved in the EEA.
The database is designed to support the collection, reporting, coding and evaluation of data on medicines in a standardised and structured way.
XEVMPD is based on information provided by marketing authorisation holders. Its main objective is to assist pharmacovigilance activities in the European Economic Area (EEA). This enables the Agency to:
- create a list of all medicines authorised in the EU;
- accurately identify medicines, especially medicines included in reports of suspected adverse reactions;
- recode medicinal product information reported in ICSRs;
- coordinate the regulation and safety monitoring of medicines across the EU.
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Related EU legislation
- Regulation (EC) 726/2004, Article 57(2), second subparagraph
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The standard terms published by the European Pharmacopoeia Commission are applied for the coding of pharmaceutical forms of medicines and routes of administrations in ICSRs reported to EudraVigilance.
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EMA performs medical literature monitoring to screen selected medical literature, to identify suspected adverse reactions with medicines authorised in the European Union, and to enter the relevant information into the EudraVigilance database. This activity is defined in Article 27 of Regulation (EC) 726/2004.
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The European pharmacovigilance issues tracking tool (EPITT) is a database developed by EMA to promote the communication of pharmacovigilance and risk-management issues between the Agency and Member States. It provides access to documents related to the safety of medicinal products/substances authorised in the EEA.
While EPITT is not exclusively part of the EudraVigilance system, it provides the functionalities for medicines regulatory authorities in the EEA and EMA to track signals at EU level.
Related documents
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The electronic transmission of ICSRs and the access to EudraVigilance require organisations and users to be registered. This is to ensure that adequate privacy and security measures are in place and to warrant that principles of data integrity, accountability and availability are adhered to.
Organisation and user management is essential to provide access to EVWEB and EVDAS to authorised users in line with the EudraVigilance access policy.
It also enables the identification of any registered EDI partner and the implementation and monitoring of security tracking functions within the EudraVigilance database management system (EVDBMS).
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