Annual safety reporting requirements

Under the Clinical Trials Directive (CTD)

The sponsor should submit an annual safety report, in the format of a Development Safety Update Report (DSUR), to the HPRA and NREC for any trial which is ongoing in Ireland.

For further information, please see the following:

• The HPRA Guide to Clinical Trial Applications: information on the content of the DSUR, and circumstances when a DSUR is required to be submitted, and exceptions.
• Section E2F of the International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines: purpose of the DSUR and examples

Under the Clinical Trials Regulation (CTR)

The sponsor must submit an Annual Safety Report (ASR) to CTIS, where at least one trial for that investigational medicinal product (IMP) is ongoing under the CTR. This submission will cover the IMP in all clinical trials whether authorised under CTR or CTD.

The sponsor should submit an ASR every year from the start of the clinical trial in any Member State until the end of the last clinical trial conducted by the sponsor with the IMP.

The ASR documentation will not be published.

Simplified ASRs

Non-commercial sponsors conducting a single clinical trial on IMPs with a marketing authorisation in any of the EU/EEA member states, and where the SmPC is used as the reference safety information, may submit a simplified ASR based on the ICH-E2F. A CTCG simplified ASR template is available and gives detailed instructions on what information is expected and what may be omitted in this setting. 

For further information, please see the following:

• CTR questions and answers document, Q7
• Clinical Trials Information System (CTIS): online modular training programme, Module 18: how to create and submit an annual safety report and respond to related requests for information
• Section E2F of the International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines: purpose of the DSUR and examples
• CTCG clinical trial safety (includes simplified ASR template)

Reporting Suspected Unexpected Serious Adverse Reactions (SUSARs) in clinical trials (CTR and CTD)

Suspected unexpected serious adverse reactions (SUSARs) occurring during clinical trials undertaken in Ireland should be notified electronically by sponsors using the clinical trials module of the EudraVigilance database (EVCTM).  Information and training can be found on the EMA EudraVigilance training and support page.

• For trials authorised under the CTD, SUSARs should be submitted to both EVCTM and the NREC.
• For trials authorised under the CTR, SUSAR submission to EVCTM only is required.

Non-commercial sponsors

The HPRA can provide assistance to non-commercial sponsors with electronic SUSAR submission to EVCTM.  In order to facilitate the timely completion of arrangements, the request for assistance should be made when submitting a clinical trial application to CTIS by emailing medsafety@hpra.ie.  

Following successful completion of arrangements, in the event of a SUSAR, the non-commercial sponsor can send the report directly to the HPRA by submitting an online report. However, if you are experiencing issues with the online form, you can email a completed copy of the SUR-F0008 Suspected unexpected serious adverse reaction report (SUSAR) form for investigator led trials v7 to the HPRA.