Regulatory Reporting

AE listed in RSI (e.g., SmPC) for the relevant population and dose; affects expedited reporting (usually not expedited if expected).

AE not listed in RSI or occurring at different severity/frequency; typically triggers expedited reporting.

System for sending ICSRs electronically to authorities (e.g., EV Gateway, FDA ESG). Must be validated and secure.

Expedited and periodic reporting of AEs from clinical trials; follows ICH E2A, E2F, and local regulations.

Serious Unexpected Suspected Adverse Reaction; expedited reporting from clinical trials to authorities and investigators.

Document compiling clinical and nonclinical data on the IMP; used as RSI for expectedness in clinical trials.

Record of each ICSR submitted to each authority (date, case ID, authority, message ID); used for reconciliation.

Process for updating RSI (e.g., SmPC) and ensuring expedited reporting rules use current RSI.

Fatal or life-threatening unexpected reports: 7 days (EU) or 5 days (FDA) from Day 0. Other serious: 15 days.

Serious unexpected (non–fatal/life-threatening) reports: 15 days from Day 0 in EU and many other regions.

Report originating from another country; same expedited reporting obligations apply to MAH in receiving country (e.g., India).

Report originating from the same country as the reporting MAH/authority.

Single global handling of each case across regions; avoid duplicate submission and ensure consistent data.

Local affiliate of MAH in a country; may receive reports and must forward to global PV and report to local authority.

Decision whether a case meets criteria for expedited reporting (serious, unexpected, valid, within scope).

When same case is reported to multiple authorities; each submission must be correct for that authority (format, timeline).

Confirmation from authority or gateway that a submission was received (e.g., EV acknowledgment); used for reconciliation.

FDA-designated reference drug for generic equivalence; safety reporting for generics may reference RLD where appropriate.

Summary of Product Characteristics; EU labeling for prescribers. Used as RSI for post-marketing expectedness.

Documented decision on whether case is reportable (expedited/periodic) and to which authorities.

Reference safety information for development (e.g., IB); used for SUSAR expectedness.

Annual report submitted to FDA for approved drugs; includes safety summary and distribution data.

Report adding information to a previously submitted case or periodic report.

Submission indicating no reportable cases in a period (e.g., no expedited reports); some authorities require.

Update on safety (e.g., for authority request or advisory committee); may be ad hoc.

Regulatory procedure to update marketing authorization for safety reason (e.g., label change).

Opinion of Committee for Medicinal Products for Human Use; basis for EC decision on MA.

Access rights and processes for MAHs to submit and (where allowed) query EudraVigilance.

Electronic gateway for submission of ICSRs and other messages to EudraVigilance.

FDA Electronic Submissions Gateway; used for electronic submission of safety and other reports.

Authority or gateway rejects submission (e.g., technical failure, business rule); must be corrected and resubmitted.

Automated acknowledgment from authority that submission was received (and sometimes validated).

Same case submitted more than once to an authority; should be avoided; reconciliation helps detect.

Submission of follow-up information for an already reported case.

Report correcting or amending a previously submitted case; must be traceable.

Report that a previously submitted case is withdrawn (e.g., duplicate or error); notify authority as required.

Review to determine if case is reportable (expedited/periodic) and to which authorities.

Requirements that differ by authority (e.g., format, timeline, null report); must be tracked per country.

Country-specific labeling (e.g., SmPC, PIL, local PI); must be consistent with CCDS.

Same as CCDS; company core document for safety and efficacy.

Company's core safety information (often same as CCDS section 4); used as RSI.

Reaction listed in RSI (SmPC/IB); typically expected and may not trigger expedited report.

Reaction not in RSI or at different level; usually unexpected and expedited.

Change in expectedness (e.g., after label update or review); affects future expedited reporting.

When new information makes case newly reportable (e.g., serious), Day 0 may reset to date of awareness of that information.

Presentation of safety data to advisory committee (e.g., FDA Advisory Committee); preparation and follow-up.

Tracking of submission deadlines and status (PBRER, expedited, etc.) per authority.

Date by which a report must be submitted; missed deadline = deviation.

Tracking of regulatory and internal timelines (Day 0, submission date).

Document or submission in response to authority request; tracked and archived.

Set of documents submitted together (e.g., PBRER and RMP).

Submission in electronic format (e.g., E2B(R3), eCTD); required by many authorities.

Submission in paper form; still accepted in some regions or as backup.

Unique identifier for a submission (e.g., message ID from EV).

Case number assigned by authority after submission; may be in acknowledgment.

Reconciliation performed at defined intervals (e.g., monthly, with each PBRER).

Single global database holding all ICSRs for the MAH; supports global case management.

Safety information in SmPC/PI (sections 4.3, 4.4, 4.8, etc.); source of RSI.

An electronic message from a regulatory authority confirming receipt of an E2B submission and indicating whether it passed validation.

A standardized one-page form developed by the Council for International Organizations of Medical Sciences for reporting individual adverse reactions.

Adverse event reports submitted directly by healthcare professionals or patients to regulatory authorities, bypassing the pharmaceutical company.

The process of forwarding adverse event reports to partners, licensees, or other stakeholders as required by contractual agreements.

The European system for managing and analyzing information on suspected adverse reactions to medicines authorized in the European Economic Area.

The rapid submission of serious, unexpected adverse events to regulatory authorities within specified timeframes (typically 7 or 15 calendar days).

FDA's database containing adverse event reports and medication error reports submitted by manufacturers, healthcare professionals, and consumers.

An expedited safety report submitted within 15 calendar days for serious, unexpected adverse reactions from post-marketing spontaneous sources.

Country-specific adverse event reporting obligations that may differ from international standards in terms of reportability criteria, timelines, or format.

The FDA's safety information and adverse event reporting program, including Form FDA 3500A for mandatory manufacturer reporting.

The process of voiding a previously submitted ICSR, typically when it is determined to be a duplicate or invalid.

Safety reports submitted at regular intervals (e.g., annually) providing cumulative analysis of a product's safety profile.

A government agency responsible for regulating medicines, including receiving safety reports and taking regulatory action to protect public health.

The formal transmission of adverse event information to regulatory authorities through approved channels and formats.

An expedited safety report submitted within 7 calendar days for fatal or life-threatening unexpected adverse reactions.

The frequency of adverse event reports relative to drug exposure, typically expressed as reports per patient-years of exposure or per units sold.

An increase in adverse event reporting due to external factors such as media attention, Dear Healthcare Provider letters, or regulatory actions.

The systematic monitoring of regulatory submission status, acknowledgments, due dates, and compliance metrics.

A serious adverse reaction from a clinical trial that is both suspected to be caused by the investigational product and is not consistent with the Investigator's Brochure.

The phenomenon where only a fraction of actual adverse events are reported to spontaneous reporting systems, typically estimated at 1-10% of actual occurrences.