Signal management

‘Signal’ means information that emerges from one or more sources, including observations and experiments, which suggests a possible new causal link, or a new aspect of a known causal link between an intervention and an adverse reaction or a series of related adverse reactions.

A new aspect could be an increase in frequency, duration or occurrence (for example, in a particular breed of dog). A signal is nearly always based on multiple reports. If a new signal is established, the marketing authorisation holder must submit the signal via IRIS. If the marketing authorisation holder decides that the benefit-risk balance has changed and an adjustment to the SPC and package leaflet is necessary, the marketing authorisation holder must inform the authorities within 30 days. In the event of an emergency (an ‘emerging safety issue’), this must be done within three days.

The Guideline on Good Veterinary Pharmacovigilance Practices (VGVP) Module: Signal Management describes the signal management process in detail.

A signal often relates to all veterinary medicinal products that contain the same active ingredient, including combination products. Some signals might be relevant only to a certain veterinary medicinal product or to a specific indication, strength, pharmaceutical form or route of administration, while other signals may apply to an entire class of veterinary medicinal products.

Signal management is used to monitor safety following marketing authorisation, but also to check the continuing effectiveness of veterinary medicinal products. The marketing authorisation holder must conduct continuous signal management to provide an optimal guarantee of the safety of its veterinary medicinal products.

Signal detection can be conducted using an in-house database if applicable, but it must also be performed in EudraVigilance at least once a year.

At least once a year, the marketing authorisation holder must declare, for each veterinary medicinal product, that the benefit-risk balance is still positive. You can do this through an ‘annual statement’. You must submit this declaration on the IRIS platform (see EMA Pharmacovigilance and IRIS on the EMA website).

The EMA publishes due dates on its website; these are based on ATC vet codes and are the dates by which annual statements must be submitted.

Procedure for translations relating to pharmacovigilance

If you decide, based on signal management, that regulatory action is required, a signal must be submitted using the IRIS platform (see above). The same applies when you need to amend the SPC. The CVMP or CMDv (depending on the procedure) will decide whether to approve the amendment in English. You should then submit a proposed Dutch translation using the contact form on our website. You can do this by selecting ‘Other’ under ‘My question is about’, then entering ‘SPC translation resulting from signal detection’ as the subject. You should then submit a Variation requiring assessment (VRA) (classification: G.I.19) via CESP. The Dutch translation is part of the linguistic review process under the VRA.

Legal basis

Section 5 of the Veterinary Medicinal Products Regulation (Articles 73 to 81) describes the rules relating to the monitoring of veterinary medicines. Implementing Regulation (EU) 2021/1281 and the Implementing Act on Good Pharmacovigilance Practices provide more details.

More information

You can find more information on signal management in the Guideline on Good Veterinary Pharmacovigilance Practices (VGVP) Module: Signal Management. If you have any questions about signal management, contact the Veterinary Medicinal Products Unit.

Note: This Regulation has completely changed the rules relating to veterinary pharmacovigilance. It is expected that the procedures will be clarified further over the next few years, and guidance documents will be supplemented or amended. As soon as this happens, we will amend the above text. You can always find the latest information about the new pharmacovigilance rules on the EMA Pharmacovigilance website.