ICSR Submission to FDA: ICH E2B(R3) becomes mandatory from 1 April 2026

The electronic submission of Individual Case Safety Reports (ICSRs) to the FDA is moving toward the full adoption of the ICH E2B(R3) standard: from 1 April 2026, pharmacovigilance cases must be submitted exclusively in the new format. In this article, we analyze what changes in ICSR submission to FDA in ICH E2B(R3) format, how submission workflows through regulatory gateways are affected, and which technical checks pharmaceutical companies should perform.

ICH E2B(R3), defined by the International Council for Harmonisation (ICH), provides the international specifications that define the structure of Individual Case Safety Reports (ICSRs) for electronic exchange between pharmaceutical companies and regulatory authorities.

Compared to the previous ICH E2B(R2) version, the new format introduces a more extensive and standardized data structure, with stricter controls on data completeness and consistency, and a more detailed representation of patient data, suspected products, and adverse reactions.

While the ICH E2B(R3) format was introduced in Europe with the release of the new version of EudraVigilance in 2017 and officially adopted in 2022, the FDA has established a transition period from 16 January 2024 to 1 April 2026.

For many companies operating primarily in Europe, pharmacovigilance systems are already configured to submit ICSRs in ICH E2B(R3) format to EMA via EudraVigilance. However, using the same format does not mean that submissions to the FDA will automatically work in the same way.

The main differences relate primarily to the submission infrastructure:

• Gateway: EMA uses the EudraVigilance Gateway, while the FDA receives submissions through the Electronic Submissions Gateway (ESG). The ICSR format remains ICH E2B(R3) in both cases, but message header elements and transmission configurations differ depending on the infrastructure requirements.
• Authority control rules: both authorities use the ICH E2B(R3) standard, but apply different business rules and validation controls during case processing. This may lead to the rejection of reports that are formally valid for other authorities (negative acknowledgements).

For this reason, companies already submitting ICSRs to EMA in ICH E2B(R3) format should verify that their systems are correctly configured for submission to the FDA.

For pharmacovigilance professionals submitting ICSRs to the FDA, the transition to ICH E2B(R3) mainly affects the systems used to generate and submit cases.

To avoid disruptions in pharmacovigilance workflows, organizations should verify that the safety database is able to correctly generate ICH E2B(R3) messages for FDA, that data mapping from the database to the XML format fields is complete and consistent, that the submission system connected to the FDA Electronic Submissions Gateway (ESG) is properly configured, and that technical acknowledgements returned by the gateway are correctly managed.

After 1 April 2026, submissions that are not compliant with the ICH E2B(R3) format will be rejected by FDA systems and returned with a negative acknowledgement through the gateway. The pharmacovigilance process itself remains unchanged, but the systems used for generating and submitting ICSRs must be aligned with the technical reporting specifications of ICH E2B(R3).

Within the SafetyDrugs safety database, these capabilities are managed through the FDA Submission module, designed to support the submission of ICSRs to the U.S. Food and Drug Administration.

The module enables the management of the entire submission workflow: from the generation of ICSR messages compliant with the ICH E2B(R3) format, to transmission via the Electronic Submissions Gateway (ESG), and finally the receipt and management of technical acknowledgements and validation errors returned by the gateway.

For companies submitting ICSRs to the FDA, having an integrated submission infrastructure allows them to manage the transition to ICH E2B(R3) smoothly and without operational disruption to pharmacovigilance workflows.

To learn more about how the SafetyDrugs FDA Submission module supports ICSR submissions to the FDA, contact our team.