Periodic Safety Update Report
Summary
The Periodic Safety Update Report (PSUR) provides a comprehensive benefit-risk analysis integrating clinical data, real-world evidence, and safety signals collected over a defined surveillance period. This report is specifically required for implantable devices and certain high-risk medical devices. Unlike standard post-market surveillance reports, PSURs require comprehensive benefit-risk analysis that integrates clinical data, real-world evidence, and safety signals to support continued market authorization.
Why is Periodic Safety Update Report important?
Regulatory authorities mandate PSURs to ensure ongoing benefit-risk evaluation of medical devices based on real-world evidence. The PSUR demonstrates that your device’s benefits continue to outweigh risks as clinical experience accumulates. Notified bodies use PSURs to assess continued compliance with essential requirements and determine whether certificate renewals are appropriate. Failure to provide adequate PSURs can result in certificate suspension, market withdrawal, or additional surveillance requirements imposed by authorities.
Regulatory Context
While FDA doesn’t specifically require PSURs, equivalent reporting may be required for:
- Post-market surveillance studies under 21 CFR 822 requiring benefit-risk analysis
- Premarket Approval (PMA) devices requiring periodic reports under 21 CFR 814.84
- Risk Evaluation and Mitigation Strategies (REMS) assessments
- De Novo pathway devices with special controls requiring surveillance
Special attention required for:
- Class III devices requiring comprehensive safety data analysis
- Breakthrough devices with accelerated approval pathways
- Software as Medical Device requiring algorithm performance monitoring
- Combination products requiring coordinated safety assessment
While FDA doesn’t specifically require PSURs, equivalent reporting may be required for:
- Post-market surveillance studies under 21 CFR 822 requiring benefit-risk analysis
- Premarket Approval (PMA) devices requiring periodic reports under 21 CFR 814.84
- Risk Evaluation and Mitigation Strategies (REMS) assessments
- De Novo pathway devices with special controls requiring surveillance
Special attention required for:
- Class III devices requiring comprehensive safety data analysis
- Breakthrough devices with accelerated approval pathways
- Software as Medical Device requiring algorithm performance monitoring
- Combination products requiring coordinated safety assessment
Under EU MDR 2017/745:
- PSURs required for implantable devices and Class III devices (Article 86)
- Must be submitted to notified body at intervals determined during conformity assessment
- Benefit-risk analysis must integrate all available safety and performance data
- EUDAMED submission required for high-risk device categories
Special attention required for:
- Implantable devices requiring annual or biennial PSURs
- Class IIb devices in sterile or measuring functions may require PSURs
- Novel technologies with limited clinical evidence requiring enhanced monitoring
- Device grouping justification when multiple devices covered in single PSUR
Guide
Your PSUR must demonstrate systematic benefit-risk evaluation using comprehensive data analysis, statistical assessment, and clinical interpretation of accumulated evidence.
Market Data Analysis
Document device exposure by providing accurate sales volumes and patient exposure estimates across different geographic regions. Use consistent metrics throughout your PSUR (devices placed on market, patient-years of exposure, or episodes of use) to enable meaningful trend analysis.
Calculate exposure-adjusted incident rates to account for changes in market penetration. Present data for European Economic Area (EEA), Turkey, Northern Ireland, and worldwide markets separately to meet regulatory reporting requirements.
Assess device lifecycle status including first market introduction date, current market status (active, withdrawn, recalled), and any basic UDI-DI variations within your device family.
Safety Data Integration
Analyze serious incidents using IMDRF Adverse Event Terminology categories covering medical device problems (Annex A), investigation findings (Annexes B-D), health effects (Annexes E-F), and component issues (Annex G). Calculate both absolute numbers and percentage rates relative to exposure.
Evaluate trend patterns using statistical methods to identify clinically significant increases in incident frequency or severity. Document whether trends represent random variation, increased reporting awareness, or genuine safety signals requiring intervention.
Review Field Safety Corrective Actions (FSCAs) and Corrective and Preventive Actions (CAPAs) implemented during the surveillance period. Assess effectiveness of corrective measures and whether additional actions are required.
Clinical Evidence Evaluation
Integrate literature findings from your clinical evaluation activities, including new publications, clinical studies, and state-of-the-art developments that may affect your device’s benefit-risk profile.
Assess Post-Market Clinical Follow-up (PMCF) data and determine whether findings require updates to your clinical evaluation report or risk management file. Document how PMCF conclusions support continued device authorization.
Evaluate complaints and user feedback that don’t qualify as serious incidents but provide insights into device performance, user satisfaction, and real-world effectiveness.
Benefit-Risk Assessment
Conduct comprehensive benefit-risk analysis by weighing accumulated safety data against demonstrated clinical benefits. Consider whether new evidence affects your intended use, user populations, or clinical claims.
Assess data limitations including surveillance gaps, under-reporting factors, and methodological constraints that may affect your conclusions. Demonstrate scientific rigor in acknowledging uncertainties while drawing appropriate conclusions.
Determine impact on device authorization by concluding whether your benefit-risk profile remains favorable, requires enhanced monitoring, or necessitates regulatory action such as labeling updates or design modifications.
Example
Scenario: You manufacture an implantable cardiac defibrillator and prepare your biennial PSUR covering 24 months of comprehensive safety and performance monitoring across global markets.
Periodic Safety Update Report for DefibGuard Pro ICD System
1. Executive Summary This PSUR covers DefibGuard Pro ICD models DG-300 through DG-305 for the period January 1, 2023 to December 31, 2024. Analysis of 847,000 patient-years of exposure, 234 serious incidents, and comprehensive literature review confirms favorable benefit-risk profile supporting continued market authorization.
2. Device Information and Market Data
| Market Region | Total Devices Implanted | Patient-Years Exposure | Serious Incidents | Incident Rate per 1000 Patient-Years |
|---|---|---|---|---|
| EEA + TR + NI | 145,230 | 423,100 | 89 | 0.21 |
| Worldwide | 298,450 | 847,000 | 234 | 0.28 |
3. Safety Analysis
Serious Incidents by IMDRF Category:
- Medical Device Problems (Annex A): 156 incidents (66.7%)
- Health Effects (Annex E): 45 incidents (19.2%)
- Component Issues (Annex G): 33 incidents (14.1%)
4. Trend Analysis Statistical analysis using Poisson regression showed stable incident rates over the surveillance period (p = 0.34). No significant trends identified requiring immediate regulatory action.
5. Field Safety Corrective Actions One FSCA initiated (FSCA-2024-001) for battery longevity communication enhancement. Implementation achieved 94% user notification rate with positive user feedback.
6. Literature and Clinical Evidence Review of 67 new publications confirms continued clinical effectiveness for primary prevention of sudden cardiac death. Post-market clinical follow-up data from 12,500 patients demonstrates 96.2% appropriate therapy delivery rate.
7. Benefit-Risk Conclusion Based on analysis of comprehensive safety and performance data, the benefit-risk profile of DefibGuard Pro ICD System remains favorable with benefits continuing to outweigh risks. No regulatory action required beyond continued routine surveillance.