The Ten Essentials of Veterinary Pharmacovigilance

Pharmacovigilance (PV) is the science of detecting, assessing, understanding, and preventing adverse effects or any other problem related to veterinary medicinal products (VMPs). It is not a paperwork exercise triggered after a complaint arrives; it is a continuous safety oversight system that runs across the entire product lifecycle.

• Detection identifies unexpected or harmful reactions in target and non-target animals, humans, and the environment.
• Assessment evaluates the nature, frequency, and severity of adverse events (AEs).
• Understanding characterises risk factors, mechanisms, and affected populations.
• Prevention implements risk minimisation measures to protect animal health, public health, and the environment.

Veterinary PV is uniquely complex: multiple target species, food-safety implications (residues in milk, meat, eggs, honey), environmental ecotoxicology, and antimicrobial resistance (AMR) as a One Health concern all fall within its scope.

Regulation (EU) 2019/6, in force since 28 January 2022, is the core legal instrument governing veterinary medicinal products in the European Union. It replaced Directive 2001/82/EC and, as a Regulation, applies directly in all Member States without national transposition.

• Centralised PV through a Union Pharmacovigilance Database, replacing previous national silos.
• Mandatory Pharmacovigilance System Master File (PSMF) per QPPV.
• Formalised continuous signal management with annual documentation and proactive benefit-risk assessment.
• Greater transparency: public access to AE incidence data and signal outcomes.
• Explicit focus on antimicrobial resistance across the supply chain.
• Harmonised Summaries of Product Characteristics (SPCs) across Member States.

Commission Implementing Regulation (EU) 2021/1281 complements Regulation 2019/6 by laying down detailed rules on good pharmacovigilance practice (VGVP) and the format and content of the PSMF.

Since January 2021, the United Kingdom has operated independently from the EMA system. The Veterinary Medicines Directorate (VMD), an executive agency of Defra, is the UK regulator. The Veterinary Medicines Regulations (VMR) 2013, significantly amended in May 2024, now govern UK veterinary PV with a three-year compliance window running to 2027.

• Detailed Description of the Pharmacovigilance System (DDPS) replaced by the PSMF.
• Periodic Safety Update Reports (PSURs) replaced by Annual Benefit-Risk Reports (BRRs).
• All worldwide AEs for UK-authorised VMPs must be reported within 30 days.
• BRSR and PSS templates are required; VICH HL7 format is mandatory for all submissions.
• Northern Ireland cases must be submitted to both the VMD and the EMA.

Companies with products in both the EU and Great Britain must maintain dual PV strategies, including separate reporting channels and, where applicable, separate PSMFs.

The International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) is a trilateral initiative between the EU, USA, and Japan, with associated members in Australia, Canada, and others. VICH guidelines underpin almost every national veterinary PV framework.

• VICH GL24 (revised 2022) — Pharmacovigilance of VMPs: standards for AE reporting, minimum ICSR data, and electronic submission in VICH HL7 format.
• VICH GL35 (revised 2010) — PV management in the absence of an electronic database: paper-based standards and minimum datasets.
• VICH GL42 (revised 2022) — Veterinary PV in the post-approval phase: proactive monitoring, signal detection, and MAH–regulator communication.

For any company operating internationally, VICH compliance is the common denominator that allows a single PV system to meet multiple national requirements with targeted adaptations.

A compliant veterinary PV system is built on a clear division of responsibilities between the MAH, the QPPV, and the regulatory authorities.

The MAH is responsible for

• Establishing and maintaining a PV system for all authorised VMPs, documented in the PSMF and auditable at all times.
• Collecting AEs from all sources (direct reports, literature, distributors, call centres) and entering them into the Union PV Database within 30 days.
• Conducting ongoing signal detection using PV data, sales data, and literature.
• Continuously assessing benefit-risk balance and notifying authorities before any public PV announcement.
• Designating a QPPV with sufficient authority, resources, and access.

The QPPV is the cornerstone of the system

• Must reside and operate within the EU/EEA (or UK for a UK QPPV).
• One QPPV per PSMF, not per product; a Deputy QPPV must be in place.
• Accountable for PSMF maintenance, case processing, signal management, and regulatory responses.
• Must report third-country PV regulatory actions to EMA/NCAs within the applicable timeline.

Under Regulation (EU) 2019/6, an adverse event is any harmful and unintended response to a VMP in animals or humans, occurring at doses normally used or tested. A confirmed causal relationship is not required for reporting; suspicion is enough.

• Animal AEs — the most common category; expected and unexpected reactions, off-label use, overdose, reactions in in-contact or neonatal animals.
• Human AEs — accidental self-injection, skin or eye contact, ingestion, occupational exposure, or allergic reactions in people handling VMPs.
• Environmental AEs — ecotoxicological incidents, contamination of water, soil, or food chain, effects on non-target species, residues in food products.
• Lack of Efficacy (LOE) — the product fails to achieve its intended effect; especially monitored for antiparasitics, antimicrobials, and vaccines.

A valid ICSR requires four minimum elements: an identifiable reporter, an identifiable patient (species is mandatory), a suspect VMP, and at least one adverse event.

Regulation (EU) 2019/6 and the 2024 UK VMR amendment eliminated the former 15-day/90-day split. The current regime is simpler, but the clock starts earlier than many MAHs realise.

• All adverse events (serious and non-serious; animal, human, environmental, and LOE) must be reported within 30 calendar days.
• Emerging Safety Issues (ESIs) must be notified without delay and no later than 3 working days after identification.
• Day 0 is the day any employee of the organisation (including field reps and call-centre staff) first becomes aware of the case — not the day it reaches the safety department.
• In the USA, the FDA requires 15 days for serious and unexpected AEs and a 3-day Field Alert for product defects; Canada and Australia also apply the 15-day timeline.

Late reporting of serious unexpected AEs is consistently classified as a Critical deficiency in PV inspections.

Causality assessment is the systematic evaluation of the strength of association between a VMP and an observed adverse event. It is a professional judgement, not a binary yes/no, and must be documented for every ICSR.

• Probable (A) — plausible temporal relationship, consistent with known pharmacology, resolved on dechallenge, no alternative explanation.
• Possible (B) — reasonable temporal relationship, partially consistent, outcome unclear on dechallenge, alternative causes plausible.
• Unlikely (N) — weak temporal relationship, inconsistent with the known profile, alternative cause more likely.
• Unassessable (O) — insufficient information or conflicting data; follow-up required.

Six factors are weighed in every assessment: temporal relationship, dechallenge, rechallenge, biological plausibility, exclusion of alternative causes, and prior information. A positive rechallenge is the strongest evidence of causality.

The Veterinary Dictionary for Drug Related Affairs (VeDDRA), developed by EMA and VICH, is the standardised controlled terminology used to code adverse events in ICSRs. It is mandatory for EU submissions and is the operational backbone of signal detection.

• SOC — System Organ Class (e.g. Nervous system disorders).
• HLGT / HLT — High Level Group Term / High Level Term (e.g. Abnormal behaviour).
• PT — Preferred Term (e.g. Ataxia) — the level used for all ICSR submissions.
• LLT — Lowest Level Term (e.g. Incoordination of movements).

Verbatim reporter language must always be retained alongside the coded term. Medically Important Terms (anaphylaxis, convulsion, hepatic failure, death) always trigger priority signal review, even where statistical thresholds are not met.

Electronic infrastructure is the operational backbone of modern veterinary PV. The EU system rests on three interconnected components, all coordinated by EMA and subject to validation under GxP (GAMP 5) principles.

• Union Pharmacovigilance Database — the central EU repository for all veterinary ICSR data (Article 74), with role-based access for MAHs, NCAs, and EMA.
• EVVet — EMA's electronic submission platform based on the VICH E2B(R3) XML standard; EVWeb is the entry interface and EVVet DWH the analytics tool for signal detection.
• IRIS — EMA's secure portal for scientific and regulatory procedures: signal evaluations, inspection outcomes, and direct MAH–EMA communication.

All computerised systems must be validated (IQ/OQ/PQ) with full audit trails and compliance with ALCOA+ data integrity principles. Documentation is not bureaucracy — it is the evidence that regulators inspect and rely upon.