EudraVigilance is the key organizational construct for the European Economic Area (EEA) and is anchored by a central database containing safety reporting (adverse events) and suspected unexpected serious adverse reactions (SUSARs) for marketed products and investigational drugs in clinical trials. By 4Q2017, EudraVigilance contained “more than 12.45 million safety reports, referring to 7.95 million cases, as well as information on 744,219 medicinal products on the EU market.”1 Reporting of events in the form of individual case safety reports (ICSRs) as a part of EudraVigilance has been ongoing for several years; however, the requirement to use the EudraVigilance data to determine drug safety is a new regulation on the horizon.
The Commission Implementing Regulation (EU) No 520/2012 (Article 18) requires EMA, national competent authorities (NCAs), and marketing authorization holders (MAHs) to continuously monitor the data available in EudraVigilance. This requirement is being implemented in two phases – the first is a pilot period, which requires EudraVigilance monitoring for a subset of nearly 300 active substances whose responsible MAHs must inform the European Medicines Agency (EMA) and NCAs of validated signals detected when monitoring the database. This pilot is being used to gauge program effectiveness prior to the full implementation of the requirements. After the pilot completes (expected in 2020), all MAHs will need to monitor the active substances they are responsible for in EudraVigilance. This requirement also fully extends to those with generic and biosimilar products.
Monitoring in EudraVigilance has two components – the first requires that MAHs download ICSRs added to EudraVigilance for their products. The second component, called the Electronic Reaction Monitoring Report (eRMR), provides an overview of adverse events reported for a specific active substance. This report includes information on the underlying cases for a particular adverse event, as well as disproportionality scores and a categorization to determine if that adverse event meets the criteria for a signal of disproportionality. In addition to the disproportionality statistics, the eRMRs also include components to allow a more clinical review – including the Important Medical Events (IME) and Designated Medical Events (DME) lists, report outcome, and a volume of other useful information. The eRMRs must be reviewed for any signals of disproportionate reporting (SDRs), as well as adverse events meeting certain clinical criteria.
As the end of the pilot period gets closer, sponsors need to consider how eRMRs coming from EudraVigilance will be retrieved and monitored, and what type of tools can be used to organize, document, and report on these suspected safety signals? The requirement to monitor drug safety in EudraVigilance is not going to be an easy change for companies, but it can be managed through the use of tools or vendors geared for pharmacovigilance in this new environment. Advance planning is key, and when EudraVigilance is fully implemented, these efforts will take human safety for clinical trials and marketed drugs to a new level in the European market.
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1https://www.ema.europa.eu/documents/other/eudravigilance-operational-pla…. Accessed 25 February 2019.
