Marketing authorisation holders (MAHs) are obliged to carry out continuous signal management of any adverse event that are reported to them throughout the period of time that their veterinary medicines are on the market. The goal is to promptly detect any new safety issues that may impact the benefit/risk balance of the product. This will ensure that proper regulatory action and communication (where necessary) can be taken. New safety issues may include a new risk associated with the product or the active substance or a change to a known risk.
MAHs should consult the EMA Guidance on veterinary good pharmacovigilance practices (VGVP guideline) for more information on this topic. At least annually, MAHs must record the outcome of the signal management process and their conclusion on the benefit/risk balance for each of their products in the Union Pharmacovigilance Database.
Note that the same pharmacovigilance requirements (including signal management) that apply to MAHs and veterinary medicines and homeopathic veterinary medicinal products also apply to those MAHs which have been granted marketing authorisations in accordance with Article 5(6) of Regulation (EU) 2019/6 (that is, for veterinary medicines for certain species kept exclusively as pets).
Signal management process and reporting responsibilities
The identification of new risks associated with a veterinary medicinal product should be based on the detection and analysis of signals, in accordance with the signal management process. The signal management process consists of, but is not limited to, the pharmacovigilance activities of signal detection, prioritisation, validation, assessment, and recommendation(s) for any action.
Signals detected by the marketing authorisation holder, regardless of the source, should be handled according to the principles outlined in the VGVP module on signal management.
An Emerging Safety Issue (ESI) is defined as any new information which might influence the assessment of the benefits and the risks of a veterinary medicinal product and which may require urgent regulatory action and communication. It should be reported to the relevant competent authority, without delay and no later than three working days after its identification.
Where the outcome of the signal management process identifies a change to the benefit/risk balance or a new risk, the marketing authorisation holder shall notify it without delay and no later than 30 calendar days to competent authorities, and where necessary submit a variation to the terms of the marketing authorisation.
Evaluation of signal management by the HPRA
The HPRA has an important role in the monitoring and assessment of signal management:
- In the evaluation of signals that are submitted continuously throughout the year by the MAHs, in order to determine which require further regulatory action.
- In the review of annual statements by MAHs of the benefit/risk balance of their veterinary medicinal product(s) together with the validated signals assessed throughout the year, which did not require urgent attention or did not lead to any proposals for further regulatory action.
The HPRA works closely with other regulatory agencies and the European Medicines Agency to facilitate a harmonised and shared approach to the evaluation of signal management.