PRAC Signal Management

A statistical alert alone, without reviewing individual cases A single spontaneous report with no timing information Case quality and completeness, temporal relationship, novelty, known product information and potential public health impact The presence of the event in a competitor's product information only

Only spontaneous reports from EudraVigilance Only literature and clinical trial data because spontaneous reports are too uncertain Relevant sources including EudraVigilance, national systems, MAH data, literature, epidemiology and international regulator information Only signals already identified by PRAC

A RACI matrix combined with documented escalation criteria, approvals and delegation records A single informal group email A policy stating that all employees share equal responsibility A requirement that only the most senior scientist may review any evidence

Close the signal permanently because evidence is incomplete Require or conduct additional evidence generation, such as a PASS, registry or targeted follow-up, with predefined methods Publish the statistical alert as proof of causality Change the label without assessing the uncertainty

A routine alert with no credible cases and no potential public health impact An emerging issue involving deaths, many cases or a novel severe reaction that may require rapid escalation A closed signal with no monitoring plan A literature search completed on schedule with no relevant findings

A shared spreadsheet with free-text entries and no change history A validated, access-controlled system with unique identifiers, timestamps, status codes, linked documents and an immutable audit trail Individual email folders maintained by each reviewer A register containing only signals that resulted in label changes

Recording that a communication was drafted Maintaining an effectiveness evaluation plan and monitoring reports with defined measures and results Archiving the PRAC recommendation without assigning an owner Updating the signal status to closed immediately after submission

The product has been proven to cause the adverse reaction A regulatory label change is automatically required The alert represents a hypothesis that requires focused validation and medical review The alert should be disregarded unless it is confirmed by a clinical trial

EMA GVP Module IX ICH E6 alone The EU Clinical Trials Regulation alone A company's internal quality manual

To complete the final benefit-risk decision for the medicine To determine rapidly whether a detected observation warrants formal assessment To draft the final SmPC and PIL wording To replace the need for case-level medical review