Safety Reporting for Auxiliary Medicinal Products in the Sibeprenlimab Phase-III Study According to the New European Union (536/2014) CT Regulation.

INTRODUCTION

The new European Union clinical trials regulation (EU CTR 536/2014) introduced the novel concept of Auxiliary Medicinal Products (AxMPs) to be implemented in clinical trials in Europe. This study aimed to understand the changes introduced under EU CTR 536/2014 with respect to AxMP requirements, implement the new regulatory mandates for Ax- MPs, and raise awareness among the sponsors on the collection, analysis, and reporting obligation of adverse events (AEs) to AxMPs.

METHODS

Using the cross-functional approach to incorporate new methods for collecting, reporting, and assessing AEs with AxMPs, the commonly prescribed AxMPs used to treat the target indication were identified. The pharmacovigilance (PV) system [safety database] was also updated to ensure appropriate AxMP-related case processing and reporting.

RESULTS

Based on impact assessment, PV processes related to safety data collection and submissions were updated to reflect EU CTR requirements for AxMPs. The study documents were updated to comply with AxMP-related regulatory obligations. World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) code level 3 was used to classify relevant AxMPs. Study drug configurations and user-defined field customizations were made to the safety database.

DISCUSSION: Otsuka submitted a Clinical Trial Application (CTA) under EU CTR for one of the ongoing clinical trials. This manuscript discusses an approach to meet the regulatory mandates for safety reporting requirements of AxMPs and provides an opportunity to implement learnings from the extensive gap analysis to internal systems and processes.

CONCLUSION

From the gap analysis and impact assessment of EU CTR, appropriate changes were made to the existing PV processes, study-specific documents, and the safety database to ensure compliance with the EU CTR.