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.
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.
- submit the MRL application at least 6 months before the marketing authorisation application;
- notify EMA in writing of the name of the substance, the intended use (indication), target species and intended target submission date, at least 6 months before the intended submission of the MRL application. If the company has a valid?micro, small and medium-sized enterprise (SME) status?or a?minor-use-minor-species and limited-markets classification, they should include this information in the notification.
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 firstname.lastname@example.org. 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:
Application form for the establishment of maximum-residue-limits for an active substance to be used in veterinary medicinal products in accordance with Regulation (EC) No. 470/2009 (PDF/78.85 KB)
First published: 26/04/2012
Last updated: 31/08/2018
Recommended submission dates for veterinary medicinal products (PDF/484.36 KB)Adopted
First published: 01/07/2009
Last updated: 11/01/2021
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.
For information on the?practical aspects?on the submission of the application and its evaluation, see :
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.
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
- a?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.
The Agency publishes the following information on MRL assessments:
- A brief statement on the adoption of an opinion recommending the establishment of an MRL in the corresponding monthly CVMP press release.
- A summary opinion of the CVMP on the MRL for those substances for which a recommendation is made to the European Commission
- The CVMP MRL opinion for substances evaluated after the entry into force of Regulation (EC) No 470/2009 on 6 July 2009.
- A European public MRL assessment report (EPMAR) containing more detailed information on the CVMP's evaluation following the publication of the Commission Regulation.
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.?
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.
Applicants should notify EMA that they intend to apply at least two months before submitting their application, by emailing the following information email@example.com:
- active substance;
- intended use;
- target species;
- intended submission date.
The evaluation has a:
- 60-day timetable if?the CVMP does not require further information?from the applicant;
- 90-day timetable if the CVMP?requires further information from the applicant?and adopts a list of questions.?
EMA charges a?fee?for evaluating the application. It invoices the fee to the applicant's?address?after?it has validated the application.
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:
Bovine casein hydrolysate : Summary of assessment undertaken to determine whether the substance may be entered into the list of biological substances considered as not requiring an MRL evaluation (PDF/123.84 KB)Adopted
First published: 29/05/2020
Recombinant bovine IL-8: Summary of assessment undertaken to determine whether the substance may be entered into the list of biological substances considered as not requiring an MRL evaluation (PDF/166.86 KB)Adopted
First published: 01/02/2021
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:
- Substances considered as not falling within the scope of regulation (EC) No 470/2009 with regard to residues of veterinary medicinal products in foodstuffs of animal origin
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: