EudraVigilance: electronic reporting

  • Email
  • Help

Marketing authorisation holders and sponsors of clinical trials must report and evaluate suspected adverse drug reactions during the development and following the marketing authorisation of medicinal products in the European Economic Area (EEA). Marketing authorisation holders must also electronically submit information on medicinal products authorised in the European Union (EU).

Reporting obligations are defined in the EU pharmacovigilance and clinical trials legislation and guidance and apply to the electronic submission and exchange of:

  • individual case safety reports (ICSRs) and acknowledgement messages in the context of clinical trials;
  • ICSRs and acknowledgement messages for centrally and non-centrally authorised medicinal products;
  • extended EudraVigilance medicinal product report messages (XEVPRMs) and acknowledgements related to information on investigational medicinal products in clinical trials;
  • XEVPRMs and acknowledgements related to information on authorised medicinal products.

On this page

 

Who needs to report what?

Interventional clinical trials

WhoWhatReference
  • Sponsors of clinical trials
  • Marketing authorisation holders
  • National competent authorities
  • Reports of suspected unexpected serious adverse reactions via safety reports (ICSRs/acknowledgements)
  • Directive 2001/20/EC
  • Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use (CT-3)
  • Sponsors of clinical trials
  • Marketing authorisation holders

 

  • Information on investigational medicinal products via product reports (XEVPRMs/acknowledgements)
  • Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use (CT-3)

Spontaneous reports and non-interventional clinical trials

WhoWhatReference
  • Marketing authorisation holders
  • National competent authorities

 

  • Reports of suspected serious adverse reactions for authorised medicinal products via safety reports (ICSRs/acknowledgements):
  • suspected serious adverse reactions occurring within
    and outside the EEA
  • suspected non-serious adverse reactions occurring
    within the EEA
  • Marketing authorisation holders
  • Information on authorised medicinal products via product reports (XEVPRMs/acknowledgements)

Back to top

 

Preparing for the electronic exchange of safety reports

EudraVigilance supports the electronic exchange of ICSRs between all electronic data interchange (EDI) partners: EMA, national competent authorities (NCAs), marketing authorisation holders (MAHs) and sponsors of clinical trials. The following steps are required for electronic transmission of ICSRs:

Step 1: Register with EudraVigilance

To complete the registration of a new organisation for the submission of ICSRs, follow the processes described in EudraVigilance: how to register.

Step 2: Obtain EudraVigilance gateway certification

Organisations need to obtain a certification to use EudraVigilance gateway. The Agency does not mandate any particular software for the electronic reporting of ICSRs, however the software needs to adhere to the standards as outlined in chapter IV of: 

Step 3: Communication test

This test will assure successful gateway-to-gateway communication. To establish the connection, organisations need to:

  • document their transport choice;
  • exchange profile information;
  • exchange public keys for encryption;
  • test the connection.

Once a successful connection has been established, safety and acknowledgement messages can be transferred between each party in the programme by sending an encrypted safety and acknowledgement message to the EV gateway. Here, it will be decrypted, checked for basic accuracy, then re-encrypted and sent to the ultimate destination.

This test is required between EMA and all organisations connected to the gateway.

Once the communication testing has been completed successfully, EMA will certify this and the organisation can move on to the next steps of testing.

Step 4: Development and validation testing

EDI partners can carry out their own development and validation testing with the external compliance testing environment (XCOMP).

Once they have completed this test phase, they will notify EMA and other potential EDI partners to move to the XML test phase.

Step 5: XML test phase

Eight sample cases need to be sent as XML files to the receiver identifier specified in the safety message as either EVTEST or EVCTMTEST in XCOMP. This will allow EMA to check if the XML files are correct and comply with the required specifications: syntax, field lengths, minimum information and data coding against ICH E2B (R2) and ICH M1 and M2 standard terminology.

To access the 8 sample test cases, perform the following steps:

  1. go to the ICSR export manager (user manual);
  2. enter 2015-07-28 as both the start date and end date;
  3. click ‘Request’ to add the report to the queue;
  4. click ‘Refresh list’ to move the report from the queue to the processed list;
  5. click ‘Download’ to save the file locally and import into own system.

The recommended method for accessing the cases is ICSR export manager because it automatically populates the message header. It may be necessary to configure the organisation’s system to include “MLMSERVICE” as a sender.

In case the ICSR export manager does not work or the user is not registered in XCOMP, this zip file containing an XML file with 8 cases may be used:

However, it may be necessary to manually set a receiving organisation identifier within the XML file.

The messages need to be loaded into the organisation’s system and then sent back to EVTEST or EVCTMTEST as applicable.

In every case a suspect medicine called ‘Spare drug’ has been included, enabling the organisation to import and process a case for its own medicine. It has ‘Spare MAH’ as the marketing authorisation holder and ‘Spare substance’ as the substance. It is optional to amend any of the fields which are populated in this section, but none of the other drug sections may be changed and no other fields may be added to this medicine. The medicine is not referenced in the narrative.

For cases 1-6, changes in no more than these sections should be necessary:

  • safety report ID (A.1.0.1);
  • receive date (A.1.6b);
  • receipt date (A.1.7b);
  • suspect medicine ‘Spare drug’ and the populated fields within that section.

For cases 7 and 8, there are specific instructions in the sender’s comment field on what follow-up to do. Testers need to send the first versions of these two ICSRs along with the other ICSRs (making the same changes as in cases 1-6), then make the required additional changes and send them again.

EMA will confirm the successful completion of the testing via email. 

Step 6: Production

EDI partners who are in the EDI process with EMA or using their locally established pharmacovigilance system need to acknowledge that for all legal and regulatory purposes, a safety or acknowledgement message or a message disposition notification (MDN) is just as valid as an equivalent paper document. 

Once all tests are successfully completed by gateway users, production can start with operational electronic transmission of ICSRs.

Any technical changes must be communicated immediately in writing between EDI partners. Major technical changes may require both test phases as described above to be re-initiated.

 

Back to top

 

Preparing for the electronic exchange of product reports

Step 1: Register with EudraVigilance

To complete the registration of a new marketing authorisation holder (MAH) and/or sponsor organisation for the submission of XEVPRMs in the new XEVPRM community, organisations should follow the processes described in: EudraVigilance: How to register.

Organisations who wish to use a local gateway can perform transmission testing and load XEVPRMs using the XCOMP environment. MAHs/sponsor organisations wishing to use EVWEB for XEVPRM submissions can skip to step 5.

Step 2: Obtain EudraVigilance gateway certification

Organisations need to obtain a certification to use the EudraVigilance gateway. EMA does not mandate any particular software for the electronic reporting of XEVPRMs, however, the software needs to adhere to the standards outlined in chapter IV of:

Step 3: Communication test

This test will assure successful gateway-to-gateway communication. To establish the connection, organisations need to:

  • document their transport choice;
  • exchange profile information;
  • exchange public keys for encryption,
  • test the connection.

Once a successful connection has been established, safety and acknowledgement messages can be transferred between each party in the programme by sending an encrypted safety and acknowledgement message to the EudraVigilance gateway. Here, it will be decrypted, checked for basic accuracy, then re-encrypted and sent to the ultimate destination.

This test is required between EMA and all organisations except national competent authorities (NCAs) – the EudraVigilance gateway already links to all NCAs in the EEA.

Once the communication testing has been completed successfully, EMA will certify this and the organisation can move on to the next stages of testing.

Step 4: Development and validation tests

Electronic data interchange (EDI) partners carry out their own development and validation testing with the external compliance testing environment (XCOMP).

This step is required to test the data exchange between EMA and the MAH/sponsor organisation. Other EDI partners may follow the same step.

Step 5: Production

EDI partners who are either in the EDI process with EMA or using their locally established pharmacovigilance system need to acknowledge that for all legal and regulatory purposes, a product or acknowledgement message or a message disposition notification (MDN) is just as valid as an equivalent paper document.

Once all tests are successfully completed by gateway users, production can start with operational electronic transmission of medicinal product messages.

Any technical changes must be communicated immediately in writing between the electronic data interchange partners. Major technical changes may require both test phases to be re-initiated.

 

Back to top

 

What to do in case of system failure

If electronic reporting of ICSRs is not possible within the expected reporting timelines due to mechanical, software, electronic or communication failures, alternative procedures should be followed:

If a system failure affects an organisation’s expected electronic reporting of ICSRs to one or more national competent authorities, NCAs also need to be informed.

To facilitate communication during a system failure, the forms listed below should be used. The numbering of the forms is not always consecutive as some are used internally by EMA or in case of additional information requests.

Back to top

 

 

 

 

 

How useful is this page?

Average rating:

 Based on 16 ratings

Add your rating:

See all ratings
7 ratings
3 ratings
2 ratings
2 ratings
2 ratings

Related content

 

Related documents

Related EU legislation