Maximum residue limits (MRL)

The maximum residue limit (MRL) is the maximum allowed concentration of residue in a food product obtained from an animal that has received a veterinary medicine or that has been exposed to a biocidal product for use in animal husbandry. The European Medicines Agency's (EMA) Committee for Medicinal Products for Veterinary Use (CVMP) is responsible for recommending MRLs, which, when adopted by the European Commission, become legally binding food safety standards. EMA provides guidance on establishing MRLs and submitting an application.

The European Union (EU) requires by law that foodstuffs such as meat, milk or eggs must not contain residue levels of veterinary medicines or biocidal products that might represent a hazard to the health of the consumer. Regulation (EC) 470/2009 lays down the rules and procedures for the establishment of MRLs.

Before a veterinary medicine intended for food-producing animals is authorised in the EU, the Committee for Medicinal Products for Veterinary Use (CVMP) evaluates the safety of its pharmacologically active substances and their residues and recommends MRLs. The Agency has published scientific guidance relevant to the establishment of MRLs for veterinary medicines.

Similarly, the CVMP is responsible for establishing MRLs for pharmacologically active substances in biocidal products for use in animal husbandry. Whilst the same principles and guidelines apply to the establishment of MRLs for pharmacologically active substances in medicines and in biocides, the Agency has published additional guidance on the risk characterisation and assessment of MRLs for biocides.

Active principles of biological origin used in immunological veterinary medicines fall outside the scope of the Regulation and are therefore exempt from an MRL evaluation.

Certain other biological substances may not require a full MRL assessment.

Substances considered not to exert pharmacological effects (non-active substances) may also be considered to fall outside the scope of the Regulation.

Submitting an MRL application

Applicants need to submit an application to EMA to have an MRL established for a new pharmacologically active substance or to extend an existing MRL to a new animal species.

EMA charges a fee for MRL applications. It may grant a total or partial fee exemption for veterinary medicines for the treatment of diseases affecting minor (food-producing) animal species.

Pre-submission guidance

    Applicants should:

    Data requirements and dossier structure are laid down in Commission Implementing Regulation (EU) 2017/12).

    Applicants can request clarification of specific issues and/or a pre-submission meeting by writing to vet.applications@ema.europa.eu. Requests for pre-submission meetings should include details of the intended application, including:

    • substance and species
    • nature of the application i.e. full application / extension / modification
    • preferred dates for pre-submission meeting
    • names and affiliation of participants
    • specific questions for discussion.

    EMA provides more pre-submission guidance in the form of questions and answers.

    Submission of the application

    For submitting an application applicants should use the MRL application form and consult the recommended submission dates:

    Applicants need to submit their application through the eSubmission Gateway / Web Client portal. For more information and guidance on registration with the system, see the Veterinary eSubmission website.

    The submission procedure is defined in Article 8 of Regulation (EC) 470/2009 and further described in Commission Implementing Regulation (EU) 2017/12.

    For information on the practical aspects on the submission of the application and its evaluation, see :

    Assessment criteria and extrapolation

    As of 19 June 2018, Commission Regulation 2018/782 describes the methodology to be used in the scientific risk assessment and establishment of risk management recommendations relevant to MRL applications. These rules replace previous guidance on MRLs in Volume 8 of “The rules governing medicinal products in the European Union" .

    As of June 2017, Commission Regulation (EU) 2017/880 sets out the principles and minimum criteria for the extrapolation of an MRL to either another foodstuff from the same species or to the same foodstuff from another species.

    When finalising an MRL evaluation, the CVMP routinely considers if its conclusions can be extrapolated to additional species and foodstuffs, regardless of whether the applicant has specifically requested this. This aims to increase the availability of veterinary medicines.

    The CVMP uses the same criteria when evaluating extension applications.

    Post-assessment

    The Agency sends the CVMP opinion on the MRL application to the European Commission, which confirms the classification of the substance by including it in the annex to Commission Regulation (EU) No 37/2010

    Substances that may be used in veterinary medicines for food-producing species or biocidal products for use in animal husbandry are listed in table 1 (allowed substances) of the annex with the following information:

    • the definitive MRL to be applied to each food commodity; or
    • provisional MRL to be applied to each food commodity. This classification is established for a defined period and only in those cases where there are no grounds for supposing that residues of the substance at the level proposed will present a hazard to the health of the consumer but where further information is still required in order to finalise the evaluation of the substance; or
    • a statement that no MRL is required - for substances where residues at the predicted levels do not pose a hazard to the health of the consumer.

    Substances considered to represent a hazard to the health of the consumer at any level are included in table 2 (prohibited substances) of the annex. These substances must not be used in veterinary medicines for food producing animals or in biocidal products for use in animal husbandry.

    Publication of information on MRLs

    The Agency publishes the following information on MRL assessments:

    Biological substances not requiring an MRL evaluation

    Update: Biological substances other than active principles of biological origin used in immunological veterinary medicines can be either 'chemical-like' or chemical-unlike'.

    'Chemical-like’ substances present similar concerns to chemical substances and are subject to a full MRL assessment.

    ‘Chemical-unlike’ substances are more complex substances that may contain multiple chemical types whose residues can be cells, amino acids, lipids, carbohydrates, nucleic acids and their breakdown products. The CVMP decides on a case-by-case basis whether 'chemical-unlike' substances require a full MRL assessment.

    For full details, see Annex I.6 of Commission Regulation (EU) 2018/782

    Applicants who consider that a biological substance is ‘chemical-unlike’ can submit an application to vet.applications@ema.europa.eu for the CVMP to evaluate the need for an MRL assessment.

      The application should include a report and supporting information explaining the scientific basis for the request. It should also address the points in Annex I.7 of Commission Regulation (EU) 2018/782.

      The evaluation follows a 90-day timetable and a fee is charged.

      When the outcome of the assessment is that the biological substance does not require a full MRL evaluation, EMA publishes a summary of the CVMP's assessment and includes the substance in the following list:

      Summaries of CVMP assessments to determine whether a substance may be included in the list of biological substances considered as not requiring an MRL evaluation

      Substances considered not to exert pharmacological effects

      Non-active ingredients considered not to exert pharmacological effects, including many excipients, are considered to fall outside the scope of the MRL Regulation.

      The CVMP determines on a case-by-case basis whether a non-active ingredient exhibits pharmacological effects and poses a risk to the consumer. If the CVMP concludes that no MRL evaluation is required, EMA includes the substance in the following list:

      Applicants who consider that a component of their product is not pharmacologically active can submit a request to the CVMP to have the substance included in the above list. For more information, see:

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