Changes in the reporting of adverse events from clinical trials - in connection with the EU Regulation 536/2014
From the 31st of January 2022, SUSARs that occurred in Hungary will only be reported to the Clinical Trial Module (EVCTM) of the EudraVigilance system. Parallel (direct) reporting to the “OGYI” organization ID will no longer be required. All SUSARs - regardless of the authorization procedure (i.e. under Directive 2001/20/EC or EU Regulation 536/2014) - should only be reported to the EVCTM, even if no trial is running with that active substance under the Regulation yet.
Concerning the Ethic Committee, SUSARs from clinical trials registered according to the Directive 2011/20/EK have to be reported to ETT-KFEB to the following e-mail address: email@example.com. SUSARs from clinical trials running according to 536/2014 EU Regulation doesn’t have to be reported to ETT-KFEB.
Annual Safety Reports
In case a clinical trial with a given active substance has been registered according to the EU Regulation 536/2014, where Hungary is member state concerned, ASR should be submitted to CTIS (Clinical Trials Information System). In this case, there is no need to report the ASR towards the Ethic Committee.
In case a clinical trial with a given active substance has been registered according to the Directive 2001/20/EC in Hungary, ASR (DSUR) should be submitted to OGYEI according to the Directive via the former submitting methods (client gate – official customer portal provided by the Hungarian government; CESP, transfer) and to the Ethic Committee (ETT-KFEB). We do not require paper copies or CDs. Submission by email is not considered official.
In case a clinical trial with a given active substance has been registered according to the Regulation in CTIS and a clinical trial with the same active substance is also running according to the Directive in Hungary, the ASR (DSUR) has to be submitted parallel: to CTIS and to OGYÉI and ETT-KFEB.
Clinical trial with a given IMP in Hungary:
clinical trial registered according to EU CTD
former submitting methods
clinical trial registered according to EU CTR
only to EMA via CTIS
Clinical trial registered according to EU CTR and clinical trial with the same active substance running according to EU CTD
- former submitting methods
- OGYÉI, ETT-KFEB
- EMA via CTIS
According to the Regulation 57/2009 1. § (3) b.) III.G.14 the regulatory fee for the assessment of ASR has to be paid at the time of the submission of the ASR. In case the clinical trial is shorter than one year, and ASR will not be submitted, the regulatory fee has to be paid at the time of the submission of the first SUSAR to EVCTM.
Urgent Safety Measures
Urgent Safety Measures (or other types of significant safety notifications) should be submitted to the CTIS if the clinical trial affected by this safety information is authorized under the Regulation.
If the safety notification relates to a study running under the Directive, the former submission procedures (client gate – official customer portal provided by the Hungarian government; CESP, transfer) should be followed. The same applies if there are already clinical trials with an active substance under the Regulation, but the given safety notification is not related to those studies.
If the safety notification relates to more studies, including some authorized under the Regulation and others under the Directive, the documentation should be submitted according to both methods in parallel.
Contact person from OGYÉI:
Dr. Anna Hajós
Q&A - Questions and answers about safety reports from clinical trials
1. Safety reports according to EU Regulation 536/2014
1) Will ETT-KFEB be notified of SUSARs coming from local CTs under EU CTR, if yes, how? Can ETT-KFEB download reports from EudraVigilance CT Module through CTIS, or will there be direct information exchange and communication between OGYÉI (NCA) and ETT-KFEB?
According to EU Regulation 536/2014 and Ministry of Health Decree 35/2005. (VIII.26.) reporting of SUSARs coming from studies under the new EU CTR shall be made to the authorizing Authority via the Agency with the help of Eudravigilance system. Assessment of SUSARs are made according to international work-sharing. Involvement of Ethic Committees in the assessment is governed by MS legislations. In Hungary the updated Decree 35/2005. (VIII. 26.) effective as from 31 Jan 2022 shall apply for studies under the EU CTR which does not require reporting of SUSARs to the ETT-KFEB and does not lay obligation for ETT KFEB to involve in the assessment of international SUSARs. ETT KFEB will not be notified of SUSARS and will not be involved in assessments.
1) Those active substances (IMPs) which are already subject to any clinical trial under EU CTR, therefore ASRs shall be submitted by Sponsor via CTIS, will ETT-KFEB or can ETT-KFEB download those ASRs, ergo can they access to those ASRs via CTIS?
ETT KFEB will not have access to ASRs uploaded via CTIS. There is no legal reporting obligation for ETT KFEB and they will not be involved in the assessments, either.
2)In Hungary at MS level will ETT-KFEB be involved in the process of safety assessment?
ETT KFEB will not be involved in the process of clinical safety assessment.
1.3. DIL/USM/ TH (Dear Investigator Letter/ Urgent Safety Measure/ Temporary Halt)
1) Will OGYÉI (NCA) and ETT-KFEB be notified such Notifications directly through CTIS?
Both OGYEI (NCA) and ETT KFEB (CEC) will directly see DIL/USM/TH Notifications submitted via CTIS.
2) Art 53 of EU CTR – Is our understanding correct that this Article refers to the first reporting, so called preliminary notification to Authority (Ref: unexpected events which affect the benefit-risk balance of the clinical trial) which will be followed by further intervention(s)? And the intervention itself depends on the ’severity’ and ’urgency’ of the unexpected event, such as amending IB (RSI), ICF, Protocol etc.
Any unexpected event affecting B:R ratio in the clinical trial but not qualifying a SUSAR, so the USM (DIL) and the TH, shall be reported without delay (within 7 days for USM – Art 54 of CTR, within 15 days for TH – Art 38 of CTR). Following this reporting further interventions may take place (risk minimization triggered amendment of IB/Protocol/Patient Leaflet etc., withdrawal of study).
1.4. Safety reports related questions to Sponsors
1) Regarding safety reports, can Sponsor receive questions exclusively from OGYÉI (NCA) or also from ETT-KFEB in CTIS? (e.g. in case of a SUSAR which occurred at a Hungarian site)
ETT-KFEB will not take part in the assessment of SUSAR and ASR. MSs shall assess these reports within work-sharing framework. Pursuant to Commission Implementing Regulation (EU) 2022/20 the safety assessor MS is required to request Sponsor to provide any necessary missing or further information required for the assessment or the MS collaboration in safety assessing.
2) In case of ASR/DSURs is it public information for which IMPs will be OGYÉI (NCA) as saMS?
Sponsors can see on their CTIS screen who the assigned saMS is.
3) Who should the Sponsor turn to in CT related safety reports and relating CTIS questions (use of assigned safety contact or firstname.lastname@example.org group e-mail address)?
In case of general safety related questions the following e-mail address can be used: email@example.com.