(a) The sponsor should submit to the regulatory authority(ies) safety updates and periodic reports, including changes to the Investigator’s Brochure, as required by applicable regulatory requirements.
(b) The sponsor should, in accordance with the applicable regulatory requirement(s) and with ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting, expedite the reporting to the regulatory authority(ies) of all suspected, unexpected and serious adverse reactions (i.e., SUSARs).
(c) Safety reporting to regulatory authorities should be undertaken by assessing the expectedness of the reaction in relation to the applicable product information (e.g., the reference safety information (RSI) contained within the Investigator’s Brochure or alternative documents) in accordance with applicable regulatory requirements. Refer to ICH E2F Development Safety Update Report for more information about RSI.
(d) The reporting of SUSARs to investigator(s)/institutions(s) and to the IRB(s)/IEC(s) should be undertaken in a manner that reflects the urgency of action required and should take into consideration the evolving knowledge of the safety profile of the product and should be performed in accordance with applicable regulatory requirements. In some regions, periodic reporting of line listings with an overall safety assessment may be appropriate.
(e) Urgent safety issues requiring immediate attention or action should be reported to the IRB/IEC and/or regulatory authority(ies) and investigators without undue delay and in accordance with applicable regulatory requirements.
(f) Alternative arrangements for safety reporting to regulatory authorities, IRBs/IECs and investigators and for reporting by investigators to the sponsor should be prospectively agreed upon with the regulatory authority(ies) and, if applicable, the IRB/IEC, and described in the clinical trial protocol (e.g., SAEs considered efficacy or safety endpoints, which would not be subject to unblinding and expedited reporting; see ICH E2A). See ICH E19 A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials.