EMA will launch a new version of EudraVigilance on 22 November 2017 with enhanced functionalities for reporting and analysing suspected adverse reactions. This has implications for all pharmacovigilance systems in the EEA, but the degree depends on your current set-up.
Pharmacovigilance, the science of monitoring medicines for potential adverse events, have traditionally been viewed as a national responsibility, but with the growing globalisation and acknowledging that adverse events are not country-specific, several measures have been put in place to ensure that the adverse events are reviewed on a larger scale. EudraVigilance is a database implemented by the EMA in the EEA countries to be able to share information easily and review it centrally to ensure signals are detected as early as possible.
With the implementation of the ICH E2B (R3) format the EudraVigilance needed updating. Now the new version has been set up and audited and a date has been set for the go-live of the new version, 22 November 2017, so now it is ready for the next step; namely for testing with individual Marketing Authorisation Holders (MAHs). National Competent Authorities (NCAs) within the EEA should also start their testing, but I will not touch further on this in this blog post.
Today, most MAHs and Sponsors of clinical trials that operates within the EEA countries have a database set-up that allows them to communicate with the Eudravigilance system. Larger MAHs/Sponsors would normally be using a safety database that can submit individual case safety reports (ICSR) directly via the E2B-gateway, whilst smaller MAHs/Sponsor would normally have two parallel systems; one system that allows them to compile aggregated reports and perform signal detection (and is not able to do E2B-reporting), and the second system consists of a direct access to a unique EudraVigilance-account for entering SUSARs from clinical trials and/or reportable post-marketing ICSRs.
Figure 1 Overview of the EudraVigilance system from http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000166.jsp
The new version of EudraVigilance from 22 November 2017 does not prompt MAHs and Sponsors to change their basic set-up. However, as the system does change significantly, it is important to make a Change Management Plan focusing on People, Technolocy, Process and Information.
For large MAHs and Sponsors that today report directly via their safety database, EudraVigilance will support reporting in E2B (R3)-format, while still maintaining the possibility of reporting in the E2B (R2)-format. But be aware that the download functionality will only be in the E2B (R3)-format, so it is necessary to be compatible with this version, if you have products on the market, to receive all European ICSRs, as they will no longer be submitted by the national competent authority.
It is therefore strongly recommendable to discuss with your database provider how to ensure that the database lives up to this format. All large database providers have known and prepared for the E2B (R3) format for a long time, so you should be ready to jump to the testing phase without much ado. For business rules regarding ICSR reporting in E2B (R2) and (R3) format, see the following:
R2: Note for guidance – EudraVigilance Human – Processing of safety messages and individual case safety reports (ICSRs) (EMA(H/20665/04/Final Rev. 2)
R3: EU Individual Case Safety Report (ICSR) Implementation Guide (EMA/51938/2013)
Testing is ready to begin at any time, since EMA has completed its internal tests. To do this it is necessary to have a test database and to be able to send in E2B (R3) format. If E2B (R3) is not fully operating yet, a test should be done with a conversion tool, and as soon as the MAH is ready to report directly via E2B (R3) the test should be redone. For the testing procedure, see EU ICSR Implementation Guide, chapter I.C.2.1.5. The test is with EMA only (no NCA-testing).
For system failure, it is no longer permitted to send CIOMS forms via fax or other methods; the MAH will need to report electronically as soon as their system is available again. If the system failure occurs in EudraVigilance, the MAH has two calendar days to re-submit after system failure has been resolved and any late cases will be excluded by compliance calculations.
Small MAHs and Sponsors of clinical trials
For smaller MAHs and Sponsors that today report directly in the EudraVigilance system by re-entering the ICSRs, it is important to use the time from now until 22 November 2017 to get accustomed with the new functionalities, and for that purpose the EMA has already now developed several tools that should help you do just that.
EMA is hosting a series of face-to-face trainings days and information days. On top of this, EMA has developed EudraVigilance and Pharmacovigilance e-learning videos, guidance documentations, user guides and webinars that are available on the webpage free of charge. Link
The main changes are that the EVWEB application will be rewritten to ensure it supports additional browsers (Firefox, Chrome, Internet Explorer version 10 or above) which will hopefully eliminate a lot of frustration moving forward, all new ICSRs are in in E2B(R3)-format only, meaning new user interface, changed data structure and additional data elements.
It is therefore strongly recommended to evaluate which information is not in the current version but will be required in the next version of EudraVigilance and ensure this information is collected routinely.
Apart from the implication on submission of ICSRs (including SUSARs) there are numerous other changes, such as changes to the duplicate detection, lack of support for submitting to other recipients via E2B-gateway, process for MLM, etc. Signal detection should be strengthened with the new version of EudraVigilance enabling MAHs access to better signal detection and analytical functions. This could be a good opportunity for smaller MAHs to strengthen their PV system.
For all types of MAHs and Sponsors of clinical trials it is strongly recommended to perform a gap analysis of existing SOPs, working instructions, etc. to ensure that the new functionalities are utilized and most importantly to ensure your pharmacovigilance system is compliant with EMA’s expectations of you – also after 22 November 2017.
Pharma IT has an expanding pharmacovigilance team consisting of senior and junior pharmacovigilance professionals as well as expertise in pharmacovigilance database system set-up and maintenance, feel free to reach out to us regarding any issue related to E2B (R3) or EudraVigilance update.