Summary: The upcoming revision of the veterinary good pharmacovigilance practices (VGVP) Module on Signal Management places greater emphasis on scientific and clinical judgement in veterinary pharmacovigilance. While quantitative analyses and automated signal detection tools can help identify potential safety concerns, assessing their clinical relevance requires a closer examination of individual case reports, biological plausibility and risk characterisation. Veterinary expertise is particularly important in interpreting findings in the context of species-specific characteristics and clinical practice.
The European Medicines Agency published Draft Revision 1 of the Guideline on veterinary good pharmacovigilance practices (VGVP) Module on Signal Management on 18 September 2026. In our previous article, we explored the key proposed changes and their practical implications for marketing authorisation holders.
One message comes through particularly clearly: signal management cannot rely on numbers alone. While automated tools and quantitative analyses support signal detection, interpreting the findings requires scientific and clinical judgement, including an understanding of the species, animal population and how the product is used in clinical practice.
How should individual cases and case series be assessed?
Individual case reports contain clinical details that cannot be fully captured through coded data or quantitative analyses alone. While screening of case narratives may be necessary only in certain situations during signal detection, for example when a small number of cases involve a large number of animals, review of individual case narratives becomes essential during signal assessment.
One notable addition to the draft is more detailed guidance on the assessment of case series. Rather than focusing only on the number of reports, the assessment considers the strength of the evidence provided by the cases collectively. Factors such as time-to-onset (TTO), dechallenge and rechallenge, alternative causes, concomitant treatments, consistency across cases and dose-response relationships may all contribute to the assessment of a potential causal association. The quality and completeness of individual reports also influence how much weight can be given to the available evidence.
An increase in reported events, for example, may appear concerning from a quantitative perspective, but closer assessment of the clinical context and how the product is used in practice may reveal other factors influencing the observed pattern.
Conversely, even a small number of well-documented cases showing a consistent and biologically plausible pattern may deserve further attention despite limited quantitative evidence.
Not all elements within the case reports need to point in the same direction. In practice, veterinary adverse event reports are often incomplete, and individual cases may contain both supporting and conflicting information. The assessment therefore requires professional judgement about how much weight should be given to each case and to the case series as a whole.
How is biological plausibility assessed in veterinary pharmacovigilance?
Assessing a signal also involves considering whether there is a biologically plausible explanation for the observed event. In veterinary medicine, this assessment may be particularly complex because susceptibility and clinical presentation can differ considerably between species, breeds and individual animals. The draft gives particular attention to pharmacological mechanisms, pharmacokinetics and toxicological findings when considering whether there is a biologically plausible explanation for an observed event.
Understanding whether an observed event fits with the known or suspected effects of a product can strengthen the evidence for a causal association. At the same time, the absence of an established mechanism does not necessarily rule out an association, particularly where scientific knowledge is still limited.
This is where veterinary expertise within the signal management team becomes valuable. A veterinarian can help to assess whether the reported clinical signs could be explained by the underlying disease, whether concomitant diseases or treatments provide an alternative explanation, or whether factors such as breed, age or physiological status could increase susceptibility to the reported event.
What should be considered in risk characterisation?
Identifying a potential association is only part of signal assessment. The draft places considerable emphasis on risk characterisation, which aims to describe the nature, seriousness and severity of the risk, the animal populations that may be particularly susceptible, when and under which conditions it occurs and, where possible, how frequently it occurs.
For veterinary medicines, this may mean looking at differences between species, breeds, age groups or animals with particular underlying conditions, but also considering factors such as dose, route of administration, off-label use, concurrent medication or even environmental and management conditions. The draft also highlights clinical course, time-to-onset, reversibility and outcome as relevant elements when defining the risk.
Expert insight: How to prepare for the revised VGVP guidance?
Although the revised guidance is still in draft form, marketing authorisation holders can already consider whether scientific and clinical judgement is adequately reflected in their current signal management processes. In particular, we recommend focusing on three areas:
- Case assessment: Ensure that signal assessment processes consider the clinical details and quality of individual case reports, rather than relying solely on quantitative findings. A structured approach can help ensure that important case-level information is not overlooked, particularly when several cases need to be evaluated together.
- Veterinary expertise: Consider involving someone with relevant clinical or veterinary knowledge early in the assessment, particularly where interpretation depends on species-specific factors, underlying disease or how the product is used in practice.
- Risk characterisation: Use a structured approach to describe the potential risk and identify remaining uncertainties. Looking separately at the affected animal population, severity and outcome, timing, conditions of use and possible risk factors can help build a clearer picture of the risk.
These considerations may help identify areas where current processes could be strengthened in preparation for the finalised guidance.
As signal detection methods continue to evolve, the draft reminds us that identifying patterns is only one part of signal management. Understanding what those patterns mean still requires scientific and clinical judgement. Veterinary expertise has an important role in bringing species-specific knowledge and practical veterinary understanding into the assessment.
If you need support with veterinary signal management or preparing for the revised guidance, Medfiles’ pharmacovigilance experts are happy to help. With over 15 years of experience in veterinary pharmacovigilance, our team provides a broad range of PV services that can be tailored to your specific needs.
Authors:
Vaiva Bužienė, veterinarian (VMD), Drug Safety Expert
Vaiva joined Medfiles Pharmacovigilance team in May 2024 and has been working with both human and veterinary PV activities in the EU and UK.
Vaiva works on global scientific literature review, signal detection and management for veterinary products and acts as a medical advisor and backup for Medfiles’ veterinary QPPVs. She also serves as the local contact person for human and veterinary PV, handling safety case reports, ensuring compliance with local regulations, and communicating with national health authorities. Her clinical experience brings valuable insight into Medfiles’ veterinary pharmacovigilance services.
Saana Lamminjoki, M.Sc. Tox., Safety Manager
Saana joined the Medfiles Pharmacovigilance team in May 2021 and has since gained extensive experience in veterinary PV, with responsibilities covering both EU and UK regulatory requirements.
She is responsible for the operational management of veterinary pharmacovigilance activities and acts as Deputy QPPV for a veterinary client company. Her day-to-day responsibilities include project management, scientific literature monitoring, signal detection and management, risk management, and the assessment and processing of adverse event reports.
Her role also covers the maintenance of the Pharmacovigilance System Master File (PSMF) and the PV Quality Management System, including the development and maintenance of veterinary pharmacovigilance procedures and processes to support ongoing regulatory compliance.
See also:
- What to know about veterinary signal management
- New EU veterinary GMP regulations: is your quality system clearly demonstrable
- How veterinary adverse event cases are managed in the EU/EEA and UK
- Best practices for maintaining a veterinary pharmacovigilance quality system
- Meet our people: Veterinarian brings valuable expertise to vet pharmacovigilance
- Veterinary QPPV ensures compliance with EU Regulation 2019/6
- Vetcare & Medfiles: Working together on the maintenance of marketing authorisations and pharmacovigilance of veterinary medicines
- Meet Medfiles’ dedicated animal health team – experts in CMC, regulatory affairs, pharmacovigilance and animal feed
