IX.C.3. Monitoring of EudraVigilance data

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IX.C.

National competent authorities and the Agency shall cooperate in the monitoring of the data available in the EudraVigilance database [IR Art 18(1)] to determine whether there are new risks or whether risks have changed and whether those risks impact on the risk-benefit balance of medicinal products [DIR Art 107h(c) and REG Art 28a(c)]. The identification of new risks or changed risks shall be based on the detection and analysis of signals [IR Art 19(1)]. Marketing authorisation holders shall monitor the data available in the EudraVigilance database to the extent that they have access to the database [IR Art 18 (2)].

IX.C.3.1. Principles for access

The principles for providing access to ICSR data held in EudraVigilance for each stakeholder group are described in the European Medicines Agency Policy on Access to EudraVigilance data for Medicinal Products for Human Use (13).

Under the policy, national competent authorities and the Agency can access all ICSR data elements without restrictions (‘ICSR Level 3’).

Marketing authorisation holders can access without restrictions all data elements of those ICSRs sent by them or resulting from the medical literature monitoring activities performed by the Agency pursuant to Article 27 of Regulation (EC) No 726/2004 (‘ICSR Level 3’). For other ICSRs held in EudraVigilance, marketing authorisation holders can request access to an extended subset of ICSR data elements including case narrative (‘ICSR data set level 2B’), upon signature of a confidentiality undertaking and confirmation that a review of ICSR data is required due to pharmacovigilance obligations, including in the context of signal management. Access to the requested data is then granted by the EudraVigilance system in a seamless way.

Relevant staff members within competent authorities and marketing authorisation holders should familiarise themselves with the guidance and training materials on EudraVigilance outputs made available online by the Agency and the training should be documented in line with the organisation’s internal procedures (see IX.B.5.).

IX.C.3.2. Periodicity of monitoring

Marketing authorisation holders, the national competent authorities and the Agency shall ensure the continuous monitoring of the EudraVigilance database with a frequency proportionate to the identified risk, the potential risks and the need for additional information on medicinal products or active substances [IR Art 18(3)].

The appropriate frequency of monitoring of EudraVigilance data may vary with the accumulation of knowledge on the risk profile of a given active substance or medicinal product, taking into account, e.g.:

  • time since first authorisation;
  • extent of patient exposure;
  • important potential risks and missing information documented in the RMP;
  • PSUR submission frequency;
  • number of ICSRs received over a given period;
  • any safety concern of interest in specific situations (e.g. vaccination campaigns).

It is recommended to monitor EudraVigilance data at least every 6 months. A more frequent monitoring is recommended for active substances contained in medicinal products included in the additional monitoring list in accordance with Article 23 of Regulation (EC) No 726/2004 (see GVP Module X), unless the sole reason for inclusion on the list is the request of a post-authorisation safety study (PASS).

Each organisation should determine the appropriate frequency for each active substance / medicinal product they monitor in EudraVigilance, taking into account the above-mentioned elements. The monitoring frequency (including any changes) and the justification thereof should be documented in accordance with the organisation’s internal procedures (see also IX.B.5.).

IX.C.3.3. Analysis of EudraVigilance data

The selection of drug-event combinations for further review should be based on scientific judgement taking into account, e.g. the number of cases and relevant statistical measures, the known safety profile of the medicinal product, the clinical relevance (e.g. important medical events), the underlying condition, the patient population and previous assessments.

Not all signals of disproportionate reporting have to be further investigated and conversely, some drug-event combinations that do not appear as signals of disproportionate reporting may warrant further investigation. Methods of routine signal detection in EudraVigilance are further discussed in Screening for adverse reactions in EudraVigilance (14).

The outputs of EudraVigilance monitoring are generally provided at the level of the active substance or combination of active substances. Scientific judgement should be applied to determine whether a particular signal may apply to all, or only some medicinal products containing an active substance. Marketing authorisation holders should consider in their analysis all ICSR data that are relevant to the safety profile of their medicinal product.

For the purpose of signal validation, a thorough analysis of EudraVigilance data should be performed taking into account any previous awareness on the signal, the strength of evidence from the cases (including narrative information) and the clinical relevance (see IX.B.3. and IX.C.4.).

Record management in relation to the monitoring and analysis of EudraVigilance data should be performed in line with the organisation’s internal procedures (see IX.B.5.).