Electronic safety reporting in clinical trials: What sponsors need to know

In today’s global regulatory landscape, electronic submission of safety reports is no longer optional; it is required. Regulatory authorities worldwide have been modernizing their systems to improve safety surveillance, increase data quality, and support more efficient analysis of adverse event information across regions. For sponsors and CROs, understanding and preparing for these changes is crucial, especially with the full enforcement of ICH E2B(R3) standards in 2026.

What is electronic safety reporting in clinical trials?

When conducting clinical trials, sponsors must report safety events such as SUSARs (Suspected Unexpected Serious Adverse Reactions) and other adverse events to regulatory authorities. Historically, these reports were often narrative-based, like PDFs or paper forms, making global signal detection and data sharing challenging.

To harmonise and standardise this process, regulators require the use of structured electronic formats, specifically ICH E2B standards for Individual Case Safety Reports (ICSRs). These standards define the structure and data elements for transmitting case-based safety information in a machine-readable format (typically XML).

Why electronic reporting matters

Electronic reporting of safety data brings real benefits:

• Data quality and consistency: structured XML messages reduce ambiguity

• Faster global signal detection: digital data enables pooling and analytics

• Automation and traceability: electronic systems speed up submissions and confirmations

• Harmonisation across regions: ICH standards align requirements across major regulatory agencies

What’s changing in 2026 with ICH E2B(R3)?

The International Council for Harmonisation (ICH) developed the E2B(R3) standard over several years, prompting regulatory authorities such as the EMA and FDA to transition to this standard for all electronic safety reporting.

Key Regulatory Milestones

• EMA (EU): ICH E2B(R3) has already been integrated into EudraVigilance and is required for safety reporting.

• FDA (US): Sponsors must use ICH E2B(R3) to submit individual safety case reports electronically by 1 April 2026. Older formats (e.g., E2B(R2) or PDF-based reporting) will no longer be accepted after this date.

These changes mean that structured, standards-compliant electronic submission is mandatory across both pre- and post-marketing safety reporting in key regions.

What sponsors must do to comply

1. Assess current safety reporting processes: Identify where legacy formats may still be in use in the submission of safety reports.

2. Implement E2B(R3)-capable system: Invest in a system that can generate valid E2B(R3) XML files and interface with regulatory submission gateways established by regulatory agencies worldwide.

3. Update SOPs and quality controls: Write or revise standard operating procedures (SOPs) to embed E2B(R3) processes, including data validation and submission workflows, and extending to clinical trials.

4. Invest in training: Ensure safety, pharmacovigilance, and regulatory teams are trained not just on the standards themselves but also on how systems generate and validate reports before submission.

5. Test and validate: Use test environments and validator tools to confirm that submissions meet the technical expectations of each agency.

How cubeSAFETY helps sponsors meet regulatory requirements

As regulators demand modern, structured safety reporting workflows, tools like cubeSAFETY are purpose-built to support sponsors with compliance, accuracy, and automation. Here’s how cubeSAFETY can help you tackle regulatory requirements into the ICH E2B(R3) era:

Built-in compliance with global standards

• Supports ICH E2B (R3) and regional requirements out of the box, ensuring that your safety data conforms to the global standard needed for regulatory submission.

• Pre-validated submission gateways to regulatory authorities (FDA, EMA, MFDS, PMDA, CDE) mean that generating and transmitting compliant XML case reports is streamlined and consistent.

Automation and quality controls

• Automated on-screen data validation and business rule checks help catch issues before submission, reducing rejections and follow-ups with regulators.

• Integrated AI medical coding assistance improves data quality and consistency at the point of entry.

Seamless integration with operational systems

• cubeSAFETY integrates with CRScube’s cubeCDMS (electronic data capture system) so that safety signals from EDC flow directly into the pharmacovigilance platform, eliminating duplication and reducing manual entry in clinical trials.

• This tight integration improves both operational efficiency and submission timelines in the treatment of adverse events.

Real-world benefits for regulatory reporting

• Sponsors have successfully transitioned from older formats (like E2B(R2)) to E2B(R3) with cubeSAFETY without operational disruption, helping to maintain compliance during regulatory transitions.

• The platform’s automation and built-in regulatory logic help reduce costs, manual workload, and the risk of submission errors, which means you can focus your teams on signal evaluation and risk management, not rework.

Final thoughts

The shift to ICH E2B(R3) and modern electronic reporting is a big step forward for patient safety and global pharmacovigilance, and it’s now a compliance requirement, including in clinical trials. Sponsors who adopt tools like cubeSAFETY put themselves in a strong position to meet regulatory expectations efficiently and with a higher degree of confidence.

With the right systems, processes, and strategic preparation, safety reporting transforms from a logistical burden into a well-controlled, compliant, and insightful component of your clinical trial operations.