Module IX of the agency's collection of GVPs (EudraLex Volume 9) introduces major procedural changes for industry. The document explains how companies should comply with their new legal obligation to continuously monitor the updated EudraVigilance database and report validated signals within strict timelines.
Furthermore, the new guideline offers greater clarity on what qualifies as an "emerging safety issue", and provides better insight into crucial terminologies such as "signal management" and "signal confirmation". It also supports a more risk-based approach when it comes to deciding how frequently the EudraVigilance database should be monitored.
The revised version of GVP module IX includes, amongst others, the following terminologies and changes:
Emerging safety issues: There is greater clarity on what qualifies as an "emerging safety issue" so that MAHs (marketing authorization holders) do not saturate the system with the transmission of less urgent information. The updated guideline states that MAHs should only communicate those safety concerns as emerging safety issues, whose urgency and seriousness cannot permit any delay in handling (i.e. prompt regulatory action and communication to patients and healthcare professionals).
Alternative processes and terminologies: The revised guideline importantly recognizes that "individual organizations may follow alternative signal management processes and terminology" that encompasses the general principles outlined in GVP module IX.
Signal validation: The guideline describes "signal validation" as the process of evaluating the data supporting a detected signal to justify its further analysis. The revised guideline states that the "extent of evaluation performed during signal validation versus further assessment may vary". This provides greater flexibility for companies to address signal validation in accordance with their internal procedures.
Signal confirmation: This refers to a regulatory step under which validated signals are submitted for an EU-level discussion by the PRAC rapporteur (Pharmacovigilance Risk Assessment Committee) or the (lead) member state.
Monitoring periodicity: The revised guideline allows companies to be flexible and use a risk-based approach when determining how frequently they should monitor EudraVigilance data, but it specifies that this should be done at least every six months. A more frequent monitoring is recommended for active substances contained in medicinal products included in the additional monitoring list (GVP module X). The monitoring frequency (including any changes) and the justification thereof should be documented in accordance with the organization’s internal procedures. This is a major change compared to the original proposal, which required the database to be checked every two weeks for products under additional monitoring, and every month for all other products.
Transition Period The requirements for MAHs to monitor EudraVigilance data and to inform the Agency and national competent authorities of validated signals will be tested in a pilot that only covers products that have a black triangle (i.e., are subject to additional monitoring). The pilot is due to start on February 22, 2018. Based on the experience from the pilot, the GVP module IX may need to be revised again. For more Information please visit the EudraLex - Volume 9 Pharmacovigilance Guidelines website.