January 15, 2026
Verifying CRO Compliance With SUSAR Reporting Timelines and Determination of Expedited vs. Standard Reporting
Suspected Unexpected Serious Adverse Reactions (SUSARs) represent one of the highest regulatory risk areas in clinical development. Health Authorities (HAs) globally, including the FDA, EMA, and national competent authorities, impose strict timelines and documentation expectations for SUSAR identification, assessment, and reporting. Sponsors frequently delegate pharmacovigilance (PV) case processing and regulatory reporting activities to Contract Research Organizations (CROs); however, regulatory accountability remains with the Sponsor.
This paper provides a structured, inspection-ready framework for Sponsors to:
- Verify whether a CRO is submitting SUSARs to Health Authorities within required timelines
- Assess whether SUSARs are correctly classified as requiring expedited or standard reporting
- Detect gaps, delays, or misclassification risks through systematic oversight, reconciliation, and audit mechanisms
The approach described aligns with FDA (21 CFR 312.32), EU Clinical Trial Regulation (EU CTR 536/2014), and ICH E2A/E2B/E2F principles.
1. Regulatory Background and Expectations
1.1 Definition of a SUSAR
A SUSAR is an adverse reaction that meets all of the following criteria:
- Serious (e.g., death, life-threatening, hospitalization, disability, congenital anomaly)
- Unexpected based on the applicable Reference Safety Information (RSI)
- Reasonably related to the investigational medicinal product (IMP)
Only cases meeting all three criteria qualify for expedited SUSAR reporting.
1.2 Regulatory Reporting Timelines
FDA (21 CFR 312.32)
- Fatal or life-threatening SUSARs: 7 calendar days (initial), with follow-up within 8 additional days
- All other SUSARs: 15 calendar days
EU / EMA (EU CTR 536/2014 & EudraVigilance)
- Fatal or life-threatening SUSARs: 7 calendar days
- Non-fatal/non-life-threatening SUSARs: 15 calendar days
Timelines are calculated from the date the Sponsor or CRO first becomes aware of the minimum reportable information.
2. Governance Model: Sponsor Oversight of CRO SUSAR Reporting
Effective verification begins with a clearly defined governance structure.
Key Sponsor expectations should be documented in:
- Pharmacovigilance Agreement (PVA) / Safety Data Exchange Agreement (SDEA)
- CRO SOPs and Working Instructions
- Sponsor Oversight SOPs
Critical governance principles include:
- Clear allocation of responsibilities for case processing, medical review, and HA submission
- Defined escalation pathways for potential SUSARs
- Transparent access to safety databases and reporting metrics
3. End-to-End SUSAR Reporting Process (CRO Perspective)
Understanding the CRO workflow is essential for verification.
3.1 Case Intake and Triage
Upon receipt of an adverse event, the CRO should:
- Log the case in the safety database
- Confirm minimum criteria (identifiable patient, reporter, event, suspect product)
- Assign an initial seriousness assessment
Verification focus:
- Date/time of initial awareness
- Consistency between source documents and database entry
3.2 Medical Assessment and SUSAR Determination
Medical review should include:
- Seriousness confirmation
- Causality assessment (related vs. not related)
- Expectedness assessment against the current RSI (IB or SmPC)
Verification focus:
- Evidence of qualified medical reviewer involvement
- Correct version of RSI used at time of assessment
- Documented rationale for causality and expectedness decisions
4. Determining Expedited vs. Standard Reporting
4.1 Decision Logic for Expedited Reporting
A case requires expedited reporting if:
- Serious = Yes
- Related = Yes or Reasonable Possibility
- Unexpected = Yes
If any criterion is not met, the case defaults to standard reporting (e.g., inclusion in DSUR, annual report, or aggregate analyses).
4.2 Common Misclassification Risks
- Using outdated RSI versions
- Downgrading causality without documented medical justification
- Inconsistent seriousness criteria application across regions
- Delayed recognition of follow-up information triggering SUSAR status
Verification focus:
- Audit trail showing reassessment when new information is received
- Consistency across similar cases
5. Verifying Timeliness of SUSAR Submissions
5.1 Timeline Reconstruction
Sponsors should independently reconstruct timelines using:
- Date of first awareness (source documents, emails, system logs)
- Date of SUSAR determination
- Date of HA submission (FDA gateway acknowledgements, EV receipts)
Any elapsed time exceeding regulatory requirements constitutes a potential compliance deviation.
5.2 Database and Submission Reconciliation
Key reconciliation activities include:
- Safety database vs. EudraVigilance/FDA submission logs
- CRO internal trackers vs. Sponsor oversight trackers
- Case-level reconciliation during audits
Verification focus:
- Missing submissions
- Late submissions
- Incorrect reporting category (7-day vs. 15-day)
6. Oversight Metrics and Key Risk Indicators (KRIs)
Sponsors should routinely monitor:
- % of SUSARs submitted within regulatory timelines
- Median days from awareness to submission
- Number of SUSAR reclassifications post-submission
- Volume of late or rejected HA submissions
Trend analysis is critical to detect systemic CRO performance issues.
7. Audit and Inspection Readiness Considerations
During audits or HA inspections, regulators commonly request:
- Line listings of SUSARs with reporting timelines
- Case narratives and medical assessments
- RSI version history
- Proof of HA submissions and acknowledgements
Sponsors should ensure CROs maintain inspection-ready documentation with complete audit trails.
8. CAPA and Continuous Improvement
When deficiencies are identified, Sponsors should require:
- Root cause analysis distinguishing process vs. training vs. system failures
- Corrective actions addressing immediate compliance gaps
- Preventive actions such as SOP updates, RSI controls, and enhanced oversight
- Effectiveness checks should include retrospective case reviews.
Conclusion
Verification of CRO SUSAR reporting is a critical Sponsor responsibility that extends beyond contractual delegation. By implementing structured oversight, independent timeline verification, and robust audit mechanisms, Sponsors can ensure timely and accurate SUSAR reporting while reducing regulatory inspection risk. A proactive, data-driven approach not only ensures compliance but strengthens overall pharmacovigilance system maturity.
