MHRA: ICSR R3 Database Go-Live May 28, Impacts UK Safety Reporting

• The MHRA's new adverse incident database, compliant with the ICH ICSR R3 standard, went live on May 28, 2024.
• All files sent from the MHRA, including acknowledgements and ASPRs, are now exclusively in the E2B R3 format, requiring Marketing Authorisation Holders to update their receiving systems.
• Incoming ICSRs will still be accepted in both R2 and R3 formats, with the new system converting R2 to R3 internally.
• Marketing Authorisation Holders are now solely responsible for conducting relevant literature searches for adverse drug reactions, including EMA MLM reports, as the MHRA will no longer publish a monitoring list.
• No changes are required for API connections or sender/receiver IDs, and MAHs do not need to notify the MHRA of their R3 readiness.

All files sent from the MHRA, including acknowledgements and ASPRs, are now exclusively in the E2B R3 format, requiring Marketing Authorisation Holders to update their receiving systems.

The Medicines and Healthcare products Regulatory Agency (MHRA) has announced the imminent go-live of its upgraded adverse incident database, a significant overhaul of its legacy IT infrastructure. This new MHRA ICSR R3 database is scheduled for deployment over the weekend of May 25 and 26, 2024, becoming fully operational from Tuesday, May 28, 2024. This transition marks a pivotal shift in how individual case safety reports (ICSRs) are processed within the UK regulatory framework.

Crucially, the new system is designed to be compliant with the ICH ICSR R3 standard and aligns with EU implementation guidance. While the MHRA will continue to accept incoming ICSRs in both the older E2B R2 and the newer E2B R3 format after the go-live, its internal processing will standardize on R3. The system will automatically convert R2 standard XMLs into the R3 standard for ingestion, ensuring compatibility during the transition period.

However, a key change for Marketing Authorisation Holders (MAHs) is that all XML files transmitted *from* the MHRA, including acknowledgements and Aggregate Safety Report (ASPR) files, will exclusively be in the E2B R3 format. The agency's new systems will no longer be capable of sending R2 files. Any ICSRs submitted before 6 am on Friday, May 24, 2024, will receive acknowledgements in R2, but all submissions made after this cutoff will be acknowledged in R3, highlighting the immediate impact of the MHRA ICSR R3 database go-live.

Marketing Authorisation Holders are mandated to submit all UK individual case safety reports (ICSRs) and serious non-UK ICSRs directly to the MHRA, utilizing either the ICSR Submissions platform or the Gateway. For cases originating from Northern Ireland, the specific country code 'XI' must be employed when sending ICSRs to the MHRA. While the Gateway will continue to accommodate both R2 and R3 XMLs for submissions and acknowledgements, MAHs must ensure their internal systems and procedures are fully equipped to receive and effectively manage files in the R3 standard.

Despite these significant changes, the MHRA has confirmed that certain aspects of the reporting process will remain consistent. There is no requirement to update sender or receiver IDs in XMLs, with the MHRA receiver ID remaining 'MHRAUK'. Furthermore, no modifications are necessary for existing application programming interface (API) connections to MHRA systems, nor do MAHs need to formally notify the agency of their R3 readiness. The MHRA will also transmit Adverse Drug Reaction (ADR) reports it receives directly to the relevant MAH, a determination made based on the suspect drug identified in the report.

Additional operational adjustments include the MHRA sending ASPRs as individual files rather than in batches. Although formal testing is not mandatory, a testing environment is available for those who wish to verify their systems' compatibility, using 'MHRAUKTEST' as the receiver ID. Users of the MHRA portal will find that it now exclusively accepts R3 XMLs via Post XML and allows the creation of new reports solely through the R3 form. Portal users will still be able to download ASPRs as PDF files, but these too will conform to the R3 standard.

A notable shift in pharmacovigilance responsibilities concerns literature monitoring. The MHRA will no longer publish a centralized literature monitoring list. Instead, Marketing Authorisation Holders are now directly accountable for proactively conducting relevant literature searches. This new approach to MHRA literature monitoring changes the landscape of how potential adverse drug reactions are identified from published sources.

MAHs must ensure that their literature search efforts are comprehensive and that any relevant reports identified are promptly submitted to the MHRA. This responsibility specifically includes incorporating reports received from the European Medicines Agency's (EMA) Medical Literature Monitoring (MLM) service. For any queries or clarifications regarding the reporting of new literature pertaining to adverse drug reactions, MAHs are directed to contact vigilanceservice@mhra.gov.uk.

The MHRA's transition to its new adverse incident database and the mandatory adoption of the MHRA E2B R3 format for outgoing communications necessitate a thorough review and update of pharmacovigilance systems and procedures by Marketing Authorisation Holders. Adherence to the ICH ICSR R3 standard is now paramount, particularly for receiving acknowledgements and ASPRs, which will exclusively be in the R3 format from May 28, 2024. Failure to adapt could lead to significant compliance challenges, as MAHs must be able to seamlessly integrate these R3-formatted files into their internal safety databases.

Beyond technical compatibility, the revised approach to MHRA literature monitoring changes the legal obligations for MAHs. The onus is now squarely on companies to demonstrate robust and proactive literature surveillance, including the integration of EMA MLM service reports. This requires not only updated technical systems but also revised standard operating procedures and staff training to ensure continuous compliance with UK adverse drug reaction reporting requirements. The definition of a safety signal — information on a new or known adverse event potentially caused by a medicine that warrants further investigation — underscores the critical nature of these reporting and monitoring duties.

Lawyers and compliance officers advising Marketing Authorisation Holders must ensure their clients' pharmacovigilance systems and procedures are updated to comply with the MHRA's new E2B R3 standard for ICSR submissions and acknowledgements, effective May 28, 2024, and understand the new responsibilities for literature monitoring to avoid non-compliance.

Source: Original reporting via GOV.UK