European Commission creates rules for allocating clinical trial safety oversight

Regulatory NewsRegulatory News | 12 January 2022 |  By 

The European Commission has published an implementing regulation that details the process for picking a member state to assess information on suspected unexpected serious adverse reactions and describes their role in screening for safety signals in clinical trials.
European law requires clinical trial sponsors to report suspected unexpected serious adverse reactions to investigational medicinal products, as well as annual safety reports, to the European Medicines Agency (EMA). EMA forwards information to the affected member states, which then cooperate on the review of the data. The implementing regulation addresses how affected member states approach that task.
The situation is straightforward when an active substance is only being studied in one member state. In that situation, the reporting member state — which is proposed by the sponsor at the time of its filing — should handle the review and record assessments “in a manner that ensures transparency and enables continuity” if oversight is transferred to another member state once the molecule enters a multinational clinical trial.
Most of the implementing regulation deals with how work on multinational clinical trials is split between member states. The Commission has set out different processes for molecules that go from being tested in one member state to being studied in multiple member states, and for sponsors that submit filings or substantial modifications to more than two member states.
If a sponsor submits to two or more member states, any member state can express an interest in taking the lead on safety assessments, regardless of whether it received the application. Member states have seven days from the authorization of the trial to apply. Then, if there is more than one application, the reporting member state has five days to choose the safety assessing member state. If no applications are received, the reporting member state chooses from among the member states concerned.
Either way, the Commission is asking the reporting member state to take into account the fair division of work when selecting the safety assessing member state. Existing expertise with the active substance is another factor.
When a molecule goes from being tested in one country to being studied in multiple countries, the regulation calls for the new reporting member state to notify the original reporting member state, when necessary. The original reporting member state then follows the selection procedure outlined above.
The safety assessing member state is responsible for screening and assessing all suspected unexpected serious adverse reactions reported in the EudraVigilance database and for identifying safety concerns in relation to the active substance and the investigational medicinal product. Those tasks, and others set out in the implementing regulation, need to be performed until three months after the end of the last clinical trial in all member states concerned.
Safety assessing member states should screen the EudraVigilance database at least every 15 calendar days. The implementing regulation permits a 30-day screening schedule for investigational medicinal products with a marketing authorization in the European Union, as well as more frequent reviews “when the state of knowledge about the safety profile of the active substance or the degree of deviation in the use of the active substance from normal clinical practice so requires.”
If the safety assessing member state identifies safety concerns, it should “submit an initial assessment as soon as possible but no later than 15 days after the screening” and notify all reporting and concerned member states “without undue delay.” The Commission expects safety assessing member states to cut the timelines for assessing and reporting information “if the risk to safety of participants in a clinical trial so requires.”
The regulation also covers the role of other member states. The Commission wants the reporting and concerned member states to support safety reviews and “have the possibility to comment and raise queries on the assessments.” Member states should jointly develop “a good practice guidance describing detailed procedures for safety cooperation including corresponding timelines and the content of the assessment reports.”
Implementing Regulation


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