Swissmedic Guidance: Electronic Exchange of ICSR in E2B(R3) Format Through the B2B Gateway

Sharan Murugan
7 minutes ago
4 min read

As pharmacovigilance systems continue to move toward standardized electronic reporting, efficient and reliable exchange of Individual Case Safety Reports (ICSRs) is essential for the timely management of adverse drug reaction information. Swissmedic has established an electronic exchange process based on the ICH E2B(R3) standard for the transmission of ICSRs between Marketing Authorisation Holders (MAHs) and Swissmedic.

The Guidance for Industry on the Electronic Exchange of ICSRs in E2B(R3) Format Through B2B Gateway describes the technical and procedural requirements for MAHs participating in the bidirectional electronic exchange of post-authorisation ICSRs with Swissmedic.

Why This Guidance Is Important

The guidance provides a common framework for MAHs and Swissmedic to exchange safety reports electronically using E2B(R3). It describes the applicable reporting requirements, technical standards, gateway connection process, testing requirements, acknowledgement procedures, security measures, and actions to be taken when electronic pharmacovigilance systems become unavailable.

Swissmedic completed the transition from E2B(R2) to E2B(R3) reporting through the B2B gateway on 30 June 2026. Companies that do not meet the conditions for using the B2B gateway are expected to use the updated ElViS electronic reporting system, which is planned to support E2B(R3) by the end of 2026.

Scope and ICSR Reporting

The guidance applies to MAHs for medicinal products and therapeutic biologicals for human use marketed in Switzerland and currently covers ICSRs from the post-authorisation phase.

MAHs are required to submit applicable safety reports to Swissmedic, including Swiss spontaneous serious ICSRs and non-serious unexpected ICSRs. The reporting scope also includes applicable reports from observational or non-interventional studies, PASS, registries, compassionate use, abuse, medication errors and near misses, and certain lack-of-efficacy cases.

Specific reporting requirements also apply to Category A clinical trials and reportable reactions associated with authorised Auxiliary Medicinal Products (AxMPs).

E2B(R3) Standards and Swissmedic Requirements

Swissmedic's drug safety system is designed to be compatible with E2B(R3). The EMA E2B(R3) Implementation Guide forms the basis for the Swissmedic requirements, while the Swissmedic guidance identifies the specific deviations applicable to Switzerland.

For post-authorisation ICSRs, Swissmedic specifies notification periods of 15 days for serious cases and 60 days for non-serious cases.

The electronic exchange is bidirectional. MAHs transmit ICSRs to Swissmedic, while Swissmedic can transmit relevant ICSRs to the concerned MAH. Safety Messages and Acknowledgement Messages must follow the applicable E2B(R3) content and message specifications.

Starting Electronic Submission

MAHs must complete the required registration, technical configuration, and testing activities before moving into the operational phase.

The connection process involves three main stages:

System integration and connectivity testing in the test environment.
End-to-end business testing between the MAH and Swissmedic drug safety systems.
System configuration for the productive environment.

Compatibility testing includes different types of XML test files, including an initial report, follow-up report, non-interventional study report, literature case with an encoded literature attachment, and a nullified report.

Swissmedic does not mandate specific software for electronic ICSR communication. However, the MAH's software must be interoperable with the Swissmedic gateway, and the MAH must provide its public certificate for participation. An agreement with Swissmedic is also required where multiple MAHs intend to use a shared sender ID.

B2B Gateway and Electronic Communication

The Swissmedic B2B gateway provides the technical infrastructure for exchanging E2B files and acknowledgement information between MAHs and the Swissmedic drug safety system.

The communication process uses AS2 and HTTPS for file exchange and SOAP web services for communication between the gateway and the Swissmedic drug safety system. Message Disposition Notifications (MDNs) confirm receipt of messages.

When an MAH submits an E2B file, the B2B gateway forwards it to the Swissmedic drug safety system. Swissmedic processes the report and returns an acknowledgement that is transmitted back to the MAH through the gateway.

The same infrastructure supports the reverse process when Swissmedic sends an E2B file to an MAH.

Acknowledgement and Validation

Incoming ICSRs undergo basic validation against the specified XML schema. Correct message headers and schema references are therefore important for successful processing and acknowledgement.

The acknowledgement process can identify different outcomes:

AA – Application Acknowledgement Accept: the message was successfully processed.
AE – Application Acknowledgement Error: an error was detected and further action may be required.
AR – Application Acknowledgement Reject: a parsing error occurred and the complete transaction must be resent.
CA – Commit Accept: the ICSR was successfully loaded.
CR – Commit Reject: a fatal error prevented the ICSR from being loaded.

If a valid sender identifier cannot be detected during parsing, an acknowledgement may not be generated. MAHs should therefore monitor the absence of expected acknowledgements and take appropriate follow-up action.

Security and System Failure Management

The electronic exchange requires appropriate technical capabilities for creating, transmitting, receiving, translating, recording, and storing safety, acknowledgement, and MDN messages.

Safety and acknowledgement messages must be encrypted and digitally signed using certificates to support secure electronic transactions. Self-signed certificates are not permitted for the Swissmedic gateway connection.

The guidance also establishes procedures for system failures. When an MAH detects a malfunction in its electronic pharmacovigilance system or gateway, it should investigate the root cause and estimate the expected downtime within 24 hours.

Where downtime is expected to be five calendar days or less, Swissmedic should be informed and the MAH should ensure that cases not successfully transmitted are submitted once the system is operational again. Where downtime is expected to exceed five days, cases meeting Swissmedic's expedited reporting criteria may be transmitted through FileShare in E2B XML format following contact with Swissmedic.

As electronic pharmacovigilance becomes an increasingly important component of regulatory safety reporting, the Swissmedic E2B(R3) framework provides MAHs with a structured approach for exchanging ICSRs through the B2B gateway. Understanding the reporting scope, E2B(R3) requirements, connectivity testing, acknowledgement process, security controls, and business continuity procedures is essential for maintaining compliant and reliable electronic safety reporting in Switzerland.