Reporting of suspected serious unexpected adverse reactions to the EudraVigilance database for clinical trials with medicinal products
With the new EU Clinical Trials Regulation for medicinal products becoming applicable, SUSARs must be reported directly to the European EudraVigilance database.
This change applies to all ongoing and new clinical trials, not just clinical trials applied for under the new regulation. Therefore, all sponsors of clinical trials of medicinal products in Denmark must ensure that they have access to the EudraVigilance database.
It is a legal requirement that the sponsor must report serious unexpected adverse reactions, cf. the EU Regulation on clinical trials on medicinal products for human use (no. 536/2014 of April 16, 2014) article 42. Therefore, all sponsors must ensure that they are correctly registered in the EudraVigilance database and have the possibility to report SUSARs.
Further information about registration in the EudraVigilance system and the required organization is provided below. The Danish Medicines Agency cannot provide technical support as the system is operated by the European Medicines Agency (EMA), so please refer to the EMA service desk.
Table of contents:
1. LEGAL REQUIREMENTS FOR REPORTING SUSPECTED SERIOUS UNEXPECTED ADVERSE REACTIONS (SUSARS) IN CLINICAL TRIALS WITH MEDICINAL PRODUCTS
2. SPONSOR AND SPONSOR ORGANIZATION REGISTRATION AND ORGANIZATION IN EUDRAVIGILANCE
3. GUIDES AND SUPPORT AVAILABLE ON EUDRAVIGILANCE
4. WHAT NEEDS TO BE SUBMITTED TO THE MEDICINES AGENCY WHEN SWITCHING TO EUDRAVIGILANCE?
5. CHANGE LOG
1. Legal requirements for reporting suspected serious unexpected adverse reactions (SUSARs) in clinical trials of medicinal products
Clinical trial sponsors are obliged to promptly report suspected serious unexpected adverse reactions (SUSARs) that occur during clinical trials.
The following applies to the prompt reporting of SUSARs:
- SUSARs arising from clinical trials authorized in Denmark must be reported directly to EudraVigilance, cf. Article 40 of the Clinical Trials Regulation, and not simultaneously to the participating national member states. In future, the sponsor can only send SUSARs from trials approved under Directive 2001/20/EU to EudraVigilance
- For clinical trials approved in Denmark, the sponsor must report all SUSARs to EudraVigilance that occur with the same active pharmaceutical ingredient in other clinical trials for which the sponsor is also responsible. This applies regardless of whether the adverse reactions occur in other trials in the EU or in third countries, as long as it is the same sponsor or another sponsor that has a formal relationship with the sponsor (e.g. the same parent company), cf. Article 42 of the Clinical Trials Regulation.
- The deadline for sponsor reporting of SUSARs shall take into account the seriousness of the adverse reaction and shall be as follows:
a) in the case of fatal or life-threatening suspected serious unexpected adverse reactions, as soon as possible and in any case within seven days of the sponsor becoming aware of the adverse reaction.
b) in the case of suspected serious unexpected adverse reactions that are not fatal or life-threatening, no later than 15 days after the sponsor has become aware of the reaction.
2. Registration and organization of sponsor and sponsor organisation in EudraVigilance
To be able to report in the EudraVigilance database, the sponsor organisation must have correct user access and organisation to the EMA databases. For non-commercial sponsors, the organisation will typically be a hospital.
First of all, the sponsor organisation must be registered in EMA's Organisation Management Service (OMS), unless the organisation has already been created, which is the case for most hospitals. Then the organisation must appoint a Responsible Person (RP) in EudraVigilance who is responsible for granting user rights to the individual sponsors in the organisation. The organisation must ensure that at least one employee has completed the required online training in EudraVigilance for RPs and the corresponding competence assessment.
The EudraVigilance database is structured in such a way that the different sponsor organisations have the ability to target and restrict user access to the sensitive data reported in the system. Therefore, organisations should create so-called "Virtual Affiliates" that act as data access groups to ensure that individual employees do not have access to all of the organisation's data. This is further described in section 8.1 of the EMA EudraVigilance Registration Manual (EudraVigilance Registration Manual page 65)
Once the sponsor organisations have the above organisation in place, it is possible for individual sponsors to apply for user access in EudraVigilance. First of all, if they do not already have one, sponsors must create an EMA user account, which is the same user account that will be used for the EudraCT database (Directive trials) and the CTIS database (Regulation trials). They can then apply for an "EV Human Contributor" role in EudraVigilance and thereby gain access to report SUSARs.
3. Available guides and support on EudraVigilance
As previously mentioned, the Danish Medicines Agency does not have access to or the ability to register sponsors in the EudraVigilance database. Only the organisation's Responsible Person can grant user access to EudraVigilance and for technical assistance, please contact the EMA service desk. The EMA Service Desk requires an EMA login, which is the same as previously mentioned for the actual registration in EudraVigilance.
We refer to the EMA website on safety reporting in clinical trials where you can find links describing both legal requirements and guidelines. The entire process of organisation and registration for the organisation is described in section 8 of EMA's EudraVigilance Registration Manual.
4. Notifications and changes to protocols in connection with switching to EudraVigilance should not be submitted to the Danish Medicines Agency as substantial changes
It is not considered a substantial change to update the wording of existing protocols from the use of the Danish Medicines Agency's SUSAR e-form to direct reporting of SUSARs in EudraVigilance. Therefore, such changes should not be submitted as a substantial amendment to the Danish Medicines Agency. Nor should they be submitted for notification, unless the EudraCT form is updated with e.g. a new person responsible for SUSAR reporting.
5. Change log
April 18, 2024 - General update of website