Adverse Event

Adverse Event is any untoward medical occurrence temporally associated with a medical device or IVD, whether or not causally related (ISO 14155:2020 §3.1; ISO 20916:2019 §3.1.1). In the EU, post-market reporting uses “incident/serious incident” (MDR 2017/745 Art. 2(64)–(65)); in the U.S., events are reported under Medical Device Reporting (21 CFR 803). Applicable in clinical studies, post-market vigilance, and complaint handling.

Regulatory framework

• US (FDA): AE/SAE monitoring during IDE studies (21 CFR 812 Subpart G); post-market Medical Device Reporting for deaths, serious injuries, certain malfunctions (21 CFR 803 Subparts B–E); user facility duties (21 CFR 803 Subpart C); electronic MDR (eMDR) per 21 CFR 803.20(a)(3).
• EU (MDR/IVDR): Clinical investigations safety reporting (MDR Annex XV Ch. II–III); vigilance uses “incident/serious incident” with timelines and PMS integration (MDR Arts. 83–92; Art. 2(64)–(65)); IVDR mirrors for IVDs (IVDR Arts. 78–87; Annex XIII §7; Annex III).
• Canada (Health Canada): Mandatory Problem Reporting for events that led, or could lead, to death or serious deterioration (SOR/98-282 Part 1 §§59–61); complaint handling/recall (SOR/98-282 §§57–65).
• Japan (PMDA/MHLW): Safety reporting under PMD Act and Good Vigilance Practice (MHLW Ministerial Ordinance No. 135/2004); expedited categories defined by MHLW notices.
• Australia (TGA): Manufacturer incident reporting obligations (Therapeutic Goods (Medical Devices) Regulations 2002, r. 5.7–5.8) and TGA vigilance guidance; integration with PMS and corrective action processes.

Key elements / What it covers

• Untoward medical occurrence with temporal association; causality not required to qualify as AE (ISO 14155; ISO 20916).
• Serious adverse event (SAE) typically involves death, life-threat, hospitalization, disability, or fetal harm (ISO 14155 §3.37; MDR Annex XV Ch. III).
• Device-related malfunctions that, if they recurred, could cause serious injury (reportable in US/EU) (21 CFR 803.3; MDR Art. 87).
• Device deficiency (e.g., malfunction, use error due to design) with potential for SERIOUS AE in clinical investigations (MDR Annex XV; ISO 14155 §3.15).
• Associated data: patient/user outcome, device identifiers (UDI), lot/serial, concomitant treatments, and investigation results.

Process / How it works

• Capture & triage: Intake from complaints, clinical sites, user facilities; log with UDI and time-to-event.
• Assess: Determine seriousness, expectedness, device involvement, and malfunction risk; classify to local definitions (e.g., MDR incident vs U.S. MDR reportable event).
• Report: Submit to authorities within required timelines (e.g., US: typically 30-day MDR or 5-day for special cases, 21 CFR 803.10/803.53; EU: 2/10/15-day windows per MDR Art. 87).
• Investigate: Root cause, corrective/preventive action linkage (ISO 13485:2016 §8.5; MDR Annex III PMS).
• Trend & review: Periodic signal detection and PMS/PSUR updates (MDR Arts. 83–86; IVDR Arts. 78–81).
• Close & document: Maintain complete records and rationale (21 CFR 803.18; ISO 13485 §4.2.5).

Common pitfalls

• Treating EU “adverse event” as the reporting term post-market (should be incident/serious incident under MDR).
• Missing reportable malfunctions that could cause serious injury if they recurred (21 CFR 803.3).
• Applying causality thresholds before deciding reportability (AE definition is temporal; reporting criteria then apply).
• Incorrect timelines or clock-start (e.g., awareness date vs occurrence date).
• Weak investigations (no root cause, no linkage to CAPA/PMS) and poor UDI/traceability.

Quick checks / Tips

• Decide term first: AE/SAE (study), incident/serious incident (EU post-market), MDR-reportable event (US).
• Document seriousness rationale and malfunction risk; keep UDI and lot data complete.
• Map local timelines and responsible roles; pre-configure eMDR/EUDAMED where applicable.
• Use IMDRF codes consistently for event/device/problem to improve trending.