Environmental risk assessment of veterinary medicines
Environmental risk assessment examines the risks a veterinary medicine's use poses to the environment. Exposure screening determines whether further testing is needed, while higher-tier assessment characterises ecological hazards and informs authorisation and risk mitigation.
Exposure screening
Environmental risk assessment (ERA) has been a legal requirement in the European marketing-authorisation process for veterinary medicines since the mid-1990s. The assessment has two phases, a framework retained when Regulation (EU) 2019/6 replaced Directive 2001/82/EC on 28 January 2022.
Phase I screens for significant environmental exposure from the intended use, using VICH GL6's algorithm of 19 yes-or-no questions. A low-exposure outcome ends the assessment, as normally happens for non-food-producing animals, minor species or limited treatment of individual animals in a flock or herd. Antiparasiticides for production animals at pasture or fish in open pens progress to Phase II because high exposure is anticipated. Production-animal products also progress when predicted environmental concentration exceeds 100 μg/kg in soil or 1 μg/L in water. The “however clause” allows a product that would otherwise stop at Phase I to progress where environmental risks are known.
Higher-tier assessment and authorisation
Phase II quantifies persistence, bioaccumulation and ecosystem toxicity, with VICH GL38 providing harmonised guidance. The assessment becomes progressively more complex through Tier A for acute effects, Tier B for chronic and reproductive effects, and Tier C for refined analysis.
For each affected ecological compartment, the risk quotient divides predicted environmental concentration by predicted no-effect concentration: RQ = PEC/PNEC. A quotient below one permits the assessment to stop; a quotient above one advances it to the next tier. Persistent elevation after Tier C leads to an overall benefit–risk judgement by the Committee for Medicinal Products for Veterinary Use. A positive opinion often carries product-specific risk-mitigation measures, usually handling and administration instructions in the summary of product characteristics; a negative opinion results in refusal of authorisation.
Phase II also identifies persistent, bioaccumulative and toxic (PBT), or very persistent and very bioaccumulative (vPvB), substances. Under the former directive, this usually led to risk-mitigation and pharmacovigilance measures.
Gaps in the former directive
Three proposed standards for veterinary environmental regulation concern coverage, burden and consistency.
- The environmental risk of every marketed veterinary medicine is known.
- The technical requirements for measuring risk do not impose excessive regulatory burdens.
- Assessment conclusions are consistent and reliable across products.
Criticism of Directive 2001/82/EC held that it met none of these standards. Some older products lacked ERAs, and older assessments differed in quality and scope from newer harmonised assessments. Product-based assessment required generics to repeat assessment even where the reference product had undergone a full ERA, creating inefficiency and regulatory burden.
Article 35 allowed post-authorisation referral, but depended on member states initiating it rather than systematic identification of products needing review; by 2021 only 20 referrals had been triggered. Other criticisms concerned the lack of legally binding environmental pharmacovigilance, only partial indirect coverage through water legislation, and the exclusion of manufacturing emissions.
Changes introduced by Regulation (EU) 2019/6
The regulation retained the two-phase, product-based technical assessment and the criteria for progression. Its aims included alignment with the European Green Deal and reducing authorisation burdens while protecting public health, animal health and the environment. Article 156 required a feasibility study of an active-substance monograph system or alternative database approach to ERA.
Article 72 allows competent authorities to request additional environmental-hazard information. Authorities can request an ERA for a generic whose reference product was authorised before 1 October 2005. Critics nevertheless questioned whether reliance on authorities' initiative would identify older products systematically.
Article 37(2) permits refusal where a food-animal product is PBT or vPvB, with an exception where it is essential to prevent or control a serious animal-health risk. That provision does not apply to companion-animal products. Recital 32 recommends monitoring products posing severe environmental risk, and Recital 56 encourages adverse-event reporting when elevated concentrations are found in soil or water; recitals are not legally binding.
Products reaching Phase II
A review of 109 centrally authorised veterinary products assessed between 2005 and October 2019 found that 95% stopped at Phase I, including all 65 intended solely for companion animals. Five products underwent both phases and two were identified as potentially PBT. An eprinomectin cattle product was refused authorisation for environmental reasons in 2018; zinc-oxide products for pigs and tylosin products for calves, pigs, turkeys and chickens were withdrawn after referral. The lack of a systematic audit made it difficult to judge whether the low proportion reaching higher-tier assessment was justified.
Companion-animal exposure and public scrutiny
VICH GL6's low-exposure assumption for companion-animal medicines rests on the smaller total quantity used, but large pet populations and non-prescription access challenge that rationale. In 2020, the UK had 66 authorised fipronil-containing products for flea and tick treatment in cats and dogs, available without prescription. Evidence of fipronil contamination in waterways prompted calls to change environmental-assessment rules for companion-animal parasiticides.
The fipronil research attracted mainstream coverage and debate among lay and professional groups, while veterinary publications criticised and defended the ERA framework. Criticism also concerned commercial confidentiality taking precedence over access to assessment information. The debate points to a need for stakeholders to agree what environmental protection assessments should provide across pharmaceuticals.