hero image

EudraVigilance Stakeholder Change Management Plan: EMA Changes to EudraVigilance (EV), ICSR reporting and SUSAR reporting

On 26 October 2015, the EMA released this document. Although the title is a bit ambiguous, the content is very important. It covers changes over the next two to three years in EudraVigilance (the EU Safety Database and IT System) covering both post-authorisation (post-marketing) and clinical trial reporting of Individual Case Safety Reports (ICSRs) and SUSARs. It is a long and complex document aimed at the Member State Health Agencies (National Competent Authorities-NCAs), clinical trial sponsors and MA holders. A schematic summary of the planned changes can be found on page 4 of the document.

The various changes put in place through regulations, directives, implementation regulations and other amendments to the requirements since 2010 are forcing these changes. They include new requirements for use of ISO standards in reporting ICSRs, use of ISO IDMP terminologies, EMA medical literature monitoring, an audit of EudraVigilance and centralization of ICSR reporting in the EU with forwarding to the national health agencies.

Submission of ICSRs

Case submissions will change when the new EudraVigilance system is in place sometime in 2017 (presumably).  This means that company submissions of both clinical trial and post-marketing ICSRs will only go to EudraVigilance and not to individual member states’ health agencies. The cases will be sent by the EMA to the member states.  So in theory, companies will not have to send these cases to the national authorities. However, in this document, the EMA notes that this new system “will not prevent stakeholders from sending ICSRs to each other.” That is some countries may still require local submissions in local languages.

Post-Marketing Cases

The requirements now in place for submission of post-marketing serious cases and EEA non-serious cases will continue. Some non-EEA non-serious cases will also have be submitted. EMA notes here that cases are considered serious at the event level not the case level. This means that if any one event in a case is serious the whole case is serious. This is not new and companies should be doing this already.

Clinical Trial SUSAR Cases

This reporting becomes very complicated. Reporting of SUSARs will continue as specified in directive 2001/20/EC for three years after the clinical trials regulatiton goes into effect. (Got that?). The EMA also notes that for 12 months after the regulation goes into effect, sponsors can choose to have their trials approved via the directive rather than the regulation in which case those trials will follow the directive for three years. What this boils down to is that companies may send SUSARs only to EV or to the NCAs that approved the trial.

Clear? If not check this document.  I suspect that there will be a lot of discussion and documents “explaining” this in detail.

WHO Uppsala Monitoring Centre (WHO UMC)

This change is aimed at the NCAs which no longer will have to send cases to WHO UMC themselves as EV will do it.

Standards & Audit

EV will move to certain ISO standards including the Identification of Medical Products (ISO IDMP terminology). Before adopting these changes, EudraVigilance must undergo an audit which is now scheduled for Q3 2016. Presumably it will pass the audit with perhaps some additional changes implemented and the whole new reporting system will then start in mid-2017.

Access to the EV data analysis system will be given to MAHs for use in signal detection and analyses including ICSR forms and line listings.

Signal Management

EV will also get new functionalities for signal detection and management, data quality monitoring and electronic reaction monitoring by the NCAs and the European Commission.

New EV System Functionalities

To implement all of this, the system components must be amended and certain new ones created (e.g. for rerouting cases to other stakeholders). Some changes will be major:

and some changes will be minor (e.g. EV organization, EV gateway).

There will also be changes to the on-line system of reporting for the public and health care professionals.

Case Forwarding

As noted, EV must now be given the capabilities of forwarding ICSRs to the relevant NCAs.  This will be complex as not all cases go to all agencies.  Issues of follow-ups, duplicates, unsuccessful uploads etc. must be resolved.

Downloads of Cases to MAHs

MAHs will continue to receive cases on their products but not from national NCAs as occurs now but rather from EV.  Not all fields will be made available to the MAHs (depending on data privacy and access issues).  This will require a secure area in EV with registration by the MAHs.

Recoding of Medical Products

After the implementation of the ISO IDMP terminologies, products will need to be recoded with training of the EMA staff and vendors on the codes, new ICH E2B(R3) fields, structures and the new interface.


Some cases will be marked  “nullified” if a pre-existing case is submitted by the same organization or an affiliate.  New rules and procedures for this will be implemented.

Supporting Documentation

This includes current and documents to be developed to help stakeholders conform to the new requirements.  There is a table on pages 14-15 of this document covering the current documentation and the proposed new ones which include: download training, how to use the EV website, revision to module VI (management and reporting of ADRs) and module IX (structures and processes in signal management).  These will appear in 2016 and 2017.


If a company submits an E2B(R3) version of a case, it will not be permitted to send the follow-up in E2B(R2) format. With the new EV system in place, organizations can submit in either R2 or R3 but access to ICSR XML data in EV will be only in R3. Thus companies must be sure to have systems in place that can process R3 versions. Test files in R2 and R3 will be made available.


Manuals and training courses (eLearning and presumably live hands-on courses) will be made available.

What To Do In Case Of System Failure

A process will be put in place…..

Go-Live (Transition) Planning

This refers to the time when EV is shut down for data migration.  Processes will be put in place for other mechanisms of submission.

Stakeholder Implementation Planning

There is a long section describing the proposed testing mechanisms for the new system scheduled to be done in mid-2016 and then for the actual system implementation by all stakeholders after this.  Much will have to be done including testing, reregistration in the new system, implementation of new tools and processes to upload and download cases, data etc.

Increase in Signals

Signaling will also change for companies and other stakeholders since they have a legal obligation to monitor the data in EV and then inform the EMA and NCAs of newly “validated signals”.  The EMA states here that: “Although it is not possible to estimate the amount of validated signals that will be submitted by MAHs, it is anticipated that there will be an increase in the volume of signals that will have to be tracked, confirmed, prioritized and evaluated and therefore resources implications for the EMA, MSs and PRAC should be considered.”

There will likely, then, be a change in the amount, quality and use of data coming in from EV. If, as EMA anticipates, more signals are now found and validated, the amount of work by companies and NCAs and others may significantly increase.  If signals are urgent they will need rapid work-ups; less urgent signals may also increase and the workload build.  As EMA coyly states, there will be “resource implications”. This is highly likely as now companies and NCAs will have more data to examine and it is likely that more signals will be found.  There will be much duplication of work with signals being looked at by companies, member states’ NCAs and, presumably, EMA.  It will be interesting to see how this duplication of work with the same signal being evaluated by the sponsor(s) and many NCAs will be handled.

Change Management

The document then covers processes and training for many other areas including recoding with the ISO IDMP terminologies, duplicate testing, data quality review, medical literature monitoring, WHO UMC reporting, helpdesks, data analysis, the EV gateway, EVWEB, training of EMA staff, the EMA communication plans, change management (people, information, technology and process).

There is also a section on training and change management planning for sponsors of trials and MAHs.


This EV change is a BIG DEAL!  The changes to EudraVigilance will be major and will run (as planned now about 2-3 years). Inevitably, there will be bugs, changes along the way, new technologies (e.g. social media interactions), budget crunches, resource issues etc.

What should you do now? At the very least, read this document and decide how much it will touch your organization or your vendors or both. It is probably also worth starting to create within your organizations a mechanism (a committee or at least a designated person) to monitor what is happening and decide when the company, vendor, NCA or other stakeholder really does have to buckle down and start working to implement these changes. Some early warning on budget and resource needs in the organization for 2016 and 2017 should be done.

The efforts to achieve this will be bigger, more costly and take more time than anyone anticipates. The time is now to start “socializing” this within your organization.


Related Articles