EMA Explains How To Comply With Future EudraVigilance Reporting Requirements
This article was originally published in SRA
The European Medicines Agency has issued a document explaining the changes that drug companies will need to make to their internal processes in the near future to allow them to carry out various pharmacovigilance-related tasks, such as reporting of drug side-effects and conducting signal management, when the EudraVigilance database is updated in 20171,2.
Among other things, companies will have to amend their existing processes for reporting individual case safety reports (ICSRs) and suspected unexpected serious adverse reactions (SUSARs). In addition, they will have to develop new processes to monitor information in the EudraVigilance database to detect and validate safety signals for the products and substances for which they hold a marketing authorization.
The changes needed are explained by the EMA in its "EudraVigilance stakeholder change management plan". The agency is advising drug companies and other stakeholders to use the document as a "starting point to develop their own internal plans" to manage the changes that will take place once the revised EudraVigilance system is functional.
Francois Domergue, scientific administrator at the EMA's data standardization and analytics department, explained* that the EudraVigilance database is being updated following new requirements introduced by the EU pharmacovigilance legislation and the Clinical Trials Regulation (EU) No 536/2014. Article 40 of the Regulation requires the agency to set up and maintain an electronic database for the reporting of SUSARs and annual safety reports, as a module of the EudraVigilance database.
Submission Of ICSRs
Under the updated EudraVigilance system, companies will have the option of submitting ICSRs in the new ISO E2B(R3) format or continuing to use the E2B(R2) format.
However, if a company decides not to implement a fully compliant ISO ICSR system, it would still need to support the ability to process the new E2B(R3) format. This is because when ICSRs are made available by the EMA to marketing authorization holders for download from EudraVigilance (in accordance with the EudraVigilance access policy), they will only be available in the E2B(R3) format.
Domergue said companies should consider either implementing a fully ISO compliant system for reporting ICSRs or using a backwards/forwards conversion tool in order to support the processing of the E2B(R3) format ICSRs and acknowledgements from the EudraVigilance system. He clarified that no significant changes would be made to the EudraVigilance Gateway itself, other than being configured to accept E2B(R3) files.
Also, centralized reporting of all ICSRs will kick in when the EudraVigilance system is updated. This means that submission of ICSRs from marketing authorization holders to national competent authorities and vice-versa should stop after this point. Domergue explained that as only ICSRs that are submitted to the updated EudraVigilance database will be considered as fulfilling a marketing authorization holder's legal obligation to report adverse events, companies "should ensure that modifications to their submission systems are configured and tested well in advance."
Companies will also have to change their processes to comply with a new requirement – the mandatory reporting of non-serious adverse events from the European Economic Area within 90 days – that will kick in when the EudraVigilance system is updated. This will be in addition to the existing requirement of submitting serious cases within 15 days. "At present, the EudraVigilance database is quite skewed as it only focuses on serious events. This new requirement would help present a more balanced picture [regarding the safety profile of a drug]," explained an industry expert.
Domergue recommended that companies should aim to complete any testing of their existing systems at least six to three months before the new EudraVigilance system goes live so that there is adequate time for any issues to be addressed. To support centralized reporting of ICSRs, for example, he said companies should put plans in place to check whether they are ready to report directly to EudraVigilance before this becomes mandatory.
Also, companies that are using the EV-WEB tool to transmit ICSRs "will need to plan for an increase in resources for the manual data entry of non-serious EEA cases into EudraVigilance, taking into account that the number of non-serious cases received is generally higher than serious cases," Domergue added.
Signal Management: Expectations and Concerns
In 2017, companies will be allowed access to the EudraVigilance database for the first time and they will be legally obliged to monitor the available data and to inform the EMA and national competent authorities about any validated signals that they identify. To support companies in this task, the EMA will provide them with signal detection tools.
The initiative is expected to be especially beneficial for small companies that may not have the resources to set up their own databases to support pharmacovigilance activities. However, there are concerns around the lack of clarity on how exactly the EMA expects companies to use the data in EudraVigilance.
"It's not clear whether the EMA expects us [ie, companies] to do data mining or whether the EMA itself would do this and only expects us to build upon it. Also, there are concerns around possible duplication of effort [i.e., whether companies and the EMA would be looking at the same data to detect possible safety signals]," an industry expert told Scrip Regulatory Affairs.
The EMA, for its part, will develop a new process for the validation of signals by marketing authorization holders. This process will be designed, discussed and consulted on during the first revision of the Good Pharmacovigilance Practice (GVP) Module IX on signal management, said Domergue. Other guidance documents and training materials will be created and provided as relevant.
Submission Of SUSARs
The Clinical Trials Regulation, when it becomes applicable, will centralize the reporting of SUSARs so that companies will only have to submit such reports to EudraVigilance. The EudraVigilance system will then automatically re-route the SUSARs to the concerned national competent authorities.
The EMA clarified that small companies will continue to the have the option to report SUSARs to the national competent authority that approved the clinical trial. This would be allowed through agreements between the sponsor and the concerned national competent authority, which would then forward any SUSARs reported under such agreements to the EudraVigilance system.
EudraVigilance Audit
Before the updated EudraVigilance system becomes functional, it will be independently audited in the third quarter of 2016 to ascertain whether the required functionalities have been implemented.
The audit report will be presented to the EMA management board, which is expected to announce by the end of 2016 whether the EudraVigilance system has implemented the functionalities. Centralized reporting of ICSRs will kick in six months later (i.e., around mid-2017).
* Francois Domergue was speaking at the Drug Information Association's ninth forum for qualified persons for pharmacovigilance (QPPVs) on Oct. 13-14 in London.
References
1. EMA press release, Oct. 27, 2015, www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/10/news_detail_002426.jsp&mid=WC0b01ac058004d5c1
2. EudraVigilance stakeholder change management plan (EMA/797114/2014), Oct. 26, 2015, www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2015/10/WC500196029.pdf