Veterinary drug residues: “chemical-unlike” biological substances (cells, organisms) are now assessed by EMA for the classification “No MRL required” under Article 14 of Regulation 470/2009; until now they went onto an Agency list, outside Table 1 of Regulation 37/2010
Commission Regulation (EU) 2025/1101, published on 4 June 2025, amends Section I.7 of Annex I to Regulation (EU) 2018/782 on the methodological principles for the assessment of maximum residue limits (MRLs). When assessing a chemical-unlike biological substance, the European Medicines Agency now determines whether the classification “no maximum residue limit required” under Article 14(2)(c) of Regulation (EC) No 470/2009 is appropriate — rather than only whether a full MRL assessment is needed.
- Previous situation: under Section I.6 of Annex I to Regulation 2018/782, biological substances resembling chemical substances (e.g. cytokines, hormones, which can be produced by chemical synthesis) undergo a full MRL assessment, while chemical-unlike ones — more complex, with residues in the form of cells, amino acids, lipids, carbohydrates, nucleic acids and their breakdown products — are assessed case by case. When EMA found a full assessment unnecessary, the substance went onto a list published by the Agency, not into Table 1 of Regulation (EU) No 37/2010 listing allowed substances.
- Change: the new wording of the second paragraph of Section I.7 requires the submitted information to be assessed according to EMA guidelines “in order to establish whether the classification ‘no maximum residue limit required’ is appropriate”. Recital 6: residues of such substances mostly belong to normal food constituents — amino acids, lipids, carbohydrates — and pose no risk to public health, so they can be given that classification. The sentence on the Agency publishing a list of substances not requiring assessment has been removed.
- What the application must contain (Section I.7, unchanged): a report with the scientific justification and the nature of the substance (e.g. cell, tissue, living or killed organism) compared with similar substances to which consumers are often exposed; the mechanism of action and potency, where known; the fate of the substance in the treated animal (bioavailability, possibility of residues in food); effects in the human gastrointestinal tract; systemic availability of residues with a worst-case estimate of consumer exposure.
- Relevance for residue control laboratories: Table 1 of Regulation 37/2010 is the list of pharmacologically active substances and their MRL classification (allowed substances); biological substances exempted from a full assessment were so far only on a separate EMA list (recital 5). The regulation was adopted under Article 13(2)(a) of Regulation 470/2009, in accordance with the opinion of the Standing Committee on Veterinary Medicinal Products; it entered into force on the twentieth day after publication.