European Medicines Agency Veterinary Medicines and Inspections London, 13 October 2006 EMEA/CVMP/765/99-Rev.16 STATUS OF MRL PROCEDURES MRL assessments in the context of Council Regulation (EEC) No 2377/90 Background and legislative framework In order to protect the safety of the consumer of foodstuffs of animal origin, one of the most important principles laid down in the European Union (EU) legislation with regard to the marketing authorisation of veterinary medicines is that foodstuffs obtained from animals treated with veterinary medicinal products must not contain residues which might constitute a health hazard for the consumer. Before a veterinary medicinal product intended for food producing animals can be authorised in the EU, all pharmacologically active substances contained in the product have to undergo a safety and residues evaluation, and have to be included in Annex I, II, or III of Council Regulation (EEC) No 2377/901. The safety and residue evaluation in accordance with Regulation 2377/90 is carried out by the Committee for Medicinal Products for Veterinary Use (CVMP) of the European Medicines Agency (EMEA), supported by safety and residues experts, upon receipt of a valid application for the establishment of maximum residue limits (MRLs). Substances for which definitive MRLs have been established are included in Annex I of Regulation 2377/90. MRLs can be proposed as provisional, if all aspects are not yet fully addressed. In this case the substance is inserted in Annex III with an expiry date defining for the termination of the provisional status. However, no provisional MRLs can be proposed, if major issues with regard to safety remain to be addressed, as it must be assured that residues at the proposed levels do not present a hazard to the health of the consumer. Only, once the applicant has satisfactorily answered the outstanding questions, the substance can be included in Annex I. These questions are likely to relate to the provision of fully validated analytical methods. Where, following the evaluation, it appears that it is not necessary for the protection of public health to establish MRLs, such substance is included in Annex II. It should be noted that an entry in Annex II is not equivalent to the status "generally recognised as safe". In fact only a sub-group of Annex II substances do fall under this category. For further details on the assessment of a substance you are advised to consult the MRL Summary report of the substances concerned. Please also note that Annex II comprises a specific entry, which provides that certain substances approved in the EU as food additives with a valid E-number are considered included in Annex II without listing the substances specifically. Relevant substances falling under these provisions are e.g. vitamin C, citric acid or several sodium and potassium salts, and these substances are only mentioned in the enclosed list if an MRL application was submitted.