Research synthesis only; not medical advice. Reporting duties vary by jurisdiction, product status, actor, and event. This page explains terminology and systems; it does not diagnose an event, assess an individual case, or replace an applicable reporting framework.
Definitions
| Term | Definition (ICH E2A / CIOMS) | Not the same as |
|---|---|---|
| Adverse event (AE) | Any untoward medical occurrence after exposure; a causal relationship is not required by the definition | Adverse drug reaction or proven causality |
| Adverse drug reaction (ADR) | A noxious and unintended response for which there is at least a reasonable possibility of causality | Any event that merely follows exposure |
| Serious adverse event (SAE) | An event meeting defined regulatory outcome criteria such as death, life threat, hospitalization, disability, congenital anomaly, or intervention to prevent permanent impairment | Severe intensity |
| Unexpected adverse event | Nature or severity is not consistent with the applicable reference information | Seriousness or causality |
| Suspected unexpected serious adverse reaction (SUSAR) | A serious, suspected-related, and unexpected reaction within a clinical-trial framework | Every serious or severe event |
Seriousness concerns regulatory outcome criteria; severity concerns intensity; expectedness compares with reference information; causality assesses relationship. MedDRA coding is a separate terminology task.
- Seriousness: regulatory outcome criteria.
- Severity: intensity.
- Expectedness: consistency with reference information.
- Causality: relationship assessment.
Pharmacovigilance systems
FDA: MedWatch and FAERS
Who receives: FDA receives voluntary reports from consumers and health-care professionals and mandatory reports from regulated manufacturers under applicable rules.
What it collects: MedWatch is a reporting route; FAERS aggregates adverse-event and medication-error reports. VAERS is a separate vaccine system.
What it can show: Case patterns and potential signals for further evaluation, not incidence or proof of causality.
EMA: EudraVigilance and PRAC
Who receives: EudraVigilance receives structured Individual Case Safety Reports within the EU pharmacovigilance framework.
What it collects: Suspected adverse reactions and related case information.
What it can show: Patterns for assessment by regulators and the Pharmacovigilance Risk Assessment Committee, subject to reporting and denominator limits.
MHRA: Yellow Card
Who receives: The UK Yellow Card system receives reports from patients, professionals, and regulated organizations.
What it collects: Suspected reactions, device incidents, and defective-medicine reports within its defined scope.
What it can show: Signals that require assessment; a report does not establish that a product caused the event.
WHO: VigiBase
Who receives: National programs contribute Individual Case Safety Reports to VigiBase, maintained by the Uppsala Monitoring Centre.
What it collects: Globally contributed suspected adverse-reaction case reports.
What it can show: Cross-national patterns for evaluation, not a population incidence rate by itself.
Observation → report with minimum information → coding and case assessment → aggregate review → signal → validation and possible action. A signal is not proven causality, and spontaneous reports lack a denominator.
MedDRA coding
MedDRA organizes reported concepts from Lowest Level Term through Preferred Term, High Level Term, High Level Group Term, and System Organ Class. Coding supports aggregation but does not decide seriousness, severity, expectedness, or causality. Different terms may represent closely related clinical descriptions, so case context remains important.
Reporting obligations
Sponsors and manufacturers
Applicable product, event, jurisdiction, and framework determine expedited and periodic reporting. Periodic Benefit-Risk Evaluation Reports under ICH E2C(R2), post-authorization studies, and trial safety reports have different scope and recipients.
Investigators and health-care professionals
Investigators communicate serious events to sponsors under the governing protocol and jurisdiction. Professional reporting duties vary across jurisdictions and settings. The applicable framework—not this page—defines recipients, clocks, follow-up, and exceptions.
Oversight bodies
Regulators and ethics committees receive different information and exercise different authority. Research responsibilities connect to human-subject governance.
Signal detection and risk management
A safety signal is information suggesting a new potentially causal association or a new aspect of a known association. Evidence may come from spontaneous reports, trials, literature, or observational studies. Disproportionality methods such as reporting ratios compare patterns within reporting data, but they are screening tools rather than causal estimates.
Spontaneous reports usually lack a denominator, are subject to stimulated and selective reporting, and vary in completeness. They can identify patterns worth evaluating but generally cannot establish incidence or comparative risk.
Limitations
Temporal order is not causality. Product identity, indication, co-exposures, underlying illness, reporting quality, duplicate cases, and missing denominator data limit interpretation. Aggregate validation may lead to label changes, study requests, communications, or no action, depending on the total evidence.
Examples reported for approved peptide classes
| Approved-product context | Examples appearing in product-specific records | Context |
|---|---|---|
| Local administration-site findings | Erythema, pruritus, induration, pain, or hematoma | Frequency and clinical meaning are product-, route-, and study-specific |
| Immunogenicity | Binding or neutralizing anti-drug antibodies | Assay, molecule, and clinical consequence differ by product |
| Hypersensitivity | Urticaria, angioedema, or anaphylaxis | Product labels define the reviewed warnings and evidence |
| Local tissue effects | Lipodystrophy or scarring in selected repeated-use contexts | Does not establish a class-wide incidence or prevention instruction |
| Systemic effects | Gastrointestinal effects for selected GLP-1 products, hypoglycemia for insulin products, fluid retention for growth-hormone products | These are named product-class contexts, not transferable class rates |
See the global regulatory framework, product-quality evidence, and representative approved monographs such as semaglutide, liraglutide, and pramlintide.
Sources
ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A). 1994. https://database.ich.org/sites/default/files/E2A_Guideline.pdf
ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Periodic Benefit-Risk Evaluation Report (E2C(R2)). 2012. https://database.ich.org/sites/default/files/E2C_R2_Guideline.pdf
ICH Harmonised Guideline. Good Clinical Practice (E6(R3)). 2025. https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf
ICH Harmonised Tripartite Guideline. Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (S6(R1)). 2011. https://database.ich.org/sites/default/files/S6_R1_Guideline_0.pdf
FDA. Guidance for Industry: Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. 2005. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/good-pharmacovigilance-practices-and-pharmacoepidemiologic-assessment
EMA. Guideline on Good Pharmacovigilance Practices (GVP). EMA/876333/2011. https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/pharmacovigilance-post-authorisation/good-pharmacovigilance-practices-gvp
Uppsala Monitoring Centre. VigiBase — the WHO Global Database of Individual Case Safety Reports (ICSRs). https://www.who-umc.org/vigibase/vigibase/