Country Attribution in ICSRs: Rules, Challenges, & Best Practices

This blog features:

• Understanding Country details – Key case processing conventions
• Key Caveats in Country Attribution in ICSRs – including primary source, country of occurrence, and reporting requirements.
• Impact on ICSR Validity and Submission – how country data influences case validation, regulatory routing, and compliance timelines.

Country Conventions: Explained

Country conventions are the rules and principles used to assign and interpret country-related data. IN relation with Individual Case Safety Reports (ICSRs) for regulatory reporting, there are things to follow in processing align with country details.

Country conventions are standardized rules that govern how country information is assigned and used in ICSR reporting for regulatory compliance.

Key country elements in ICSRs

1. Primary Source Country
   • Country of the person who first reports the case
2. Country of Occurrence
   • Where the adverse event actually happened
3. Country of Receipt / Review
   • Used if primary source country is unknown

“Understanding country conventions transforms ICSR reporting from routine data entry into precise regulatory communication.”

Schedule a call

Key Points on Country Convention & ICSR Processing

1. Primary Source for Regulatory Purposes (ICH E2B R3) refers to the person who first reports the case. It is not applicable to R2 format. In multiple-source cases, it determines the country used for the worldwide unique case ID.
2. If the reaction occurs in a different country, record it under “Country Where Reaction Occurred”. Example: Patient from Ireland with a reaction in Spain → Primary country: Ireland, Occurrence: Spain.
3. For internet/digital reports, reporter identifiability requires verifiable details (e.g., valid email). If the country is missing, use the country where the report was received or reviewed.
4. An ICSR is valid only if at least one reporter is identifiable, including qualification and country (per ICH E2D and E2B).
5. If reporter country is unavailable, use the country of receipt or review.
6. Adverse reaction reports must be classified and submitted as per applicable guidance, considering seriousness and country of origin.
7. Exclusion of cases is allowed if the product was never marketed or supplied in that country and is not used as travel medicine.
8. Literature cases may be excluded if the product is authorized but never marketed in that country.
9. If a product is under evaluation in the EU but authorized elsewhere, valid ICSRs from outside the EU must still be submitted per timelines.
10. When primary source country differs from occurrence country, relevant EU authorities are automatically notified.
11. Product composition differences by region in E2B formats:
    1. R2: Use active substances matching the product in the country of occurrence
    2. R3: Use Substance/Specified Substance Name accordingly
12. Electronic retransmission involves passing ICSRs between multiple parties (e.g., non-EU MAH → EU MAH → Agency).
13. The primary reporter country can change, but the worldwide unique case ID must remain unchanged.
14. Falsified medicinal products include those with false information about source, manufacturer, origin, or distribution history.

Conclusion

Country conventions are a critical foundation of accurate ICSR reporting. Correct identification of the primary source country, country of occurrence, and, where applicable, the country of receipt ensures proper case validation, regulatory routing, and compliance with submission timelines. Misclassification can lead to reporting errors, delays, or non-compliance.

Therefore, a clear understanding and consistent application of country conventions are essential for maintaining data integrity and meeting global pharmacovigilance requirements.