Global pharmacovigilance reporting: comparative analysis of adverse event obligations across five major regulatory...

As pharmaceutical development spans multiple continents, marketing authorization holders must simultaneously comply with distinct adverse event reporting frameworks of major health authorities. Although International Council for Harmonisation guidelines provide shared foundations, meaningful differences persist in reporting timelines, case thresholds, and special-situation obligations across jurisdictions.

A narrative review of primary regulatory legislation, guidance documents, peer-reviewed literature, and International Council for Harmonisation guidelines was conducted for five major regulatory authorities: Health Canada, the U.S. Food and Drug Administration, the European Medicines Agency, Japan's Pharmaceuticals and Medical Devices Agency, and China's National Medical Products Administration. These authorities collectively represent the majority of global pharmaceutical market value and clinical trial activity, and each is either an International Council for Harmonisation founding or observer member. Comparative summary tables and decision algorithms were synthesized from authoritative sources across clinical trial, post-marketing, medical device, vaccine, and special-population reporting contexts.

All five authorities share International Council for Harmonisation seriousness criteria and require expedited seven-calendar-day reporting for fatal or life-threatening suspected unexpected serious adverse reactions in clinical trials. Key jurisdictional differences include: China's unique 24-h obligation for post-marketing deaths; the European Medicines Agency's device vigilance timelines (10 calendar days for deaths, two calendar days for serious public health threats); the Food and Drug Administration's 30-calendar-day default for manufacturer device reports; the European Medicines Agency's 90-calendar-day obligation for non-serious individual case safety reports from the European Economic Area; and Japan's 30-calendar-day timeline for serious expected domestic adverse drug reactions. The Food and Drug Administration's December 2025 final guidance on sponsor responsibilities further consolidated aggregate analysis obligations, and the proposed transition from the Investigational New Drug Annual Report to the Development Safety Update Report format signals growing emphasis on periodic safety assessment.

Effective pharmacovigilance depends on the interplay between expedited individual case reporting and aggregate periodic assessments, including Development Safety Update Reports and Periodic Benefit-Risk Evaluation Reports. A structured decision-tree approach enables marketing authorization holders to manage multi-authority reporting obligations systematically, while ongoing regulatory convergence-exemplified by global adoption of the Development Safety Update Report-reduces submission format burdens.