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.
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.
As of 27 January 2017, new requirements for data and dossier structure apply for MRL applications, including a new chapter on risk management considerations (in line with Commission Implementing Regulation (EU) 2017/12). The new dossier structure will be accepted in e-submission after EMA provides an updated application form in September 2018. EMA will provide further updates on the implementation. For more information, see the Q&As on e-submission for veterinary applications on the e-submission website.
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 (MRLs) EMA will update this application form in September 2018.
- Recommended submission dates for centralised and MRL procedures
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 EMA's standard operating procedure:
EMA provides more pre-submission guidance in the form pf questions and answers.
Applicants can request clarification of specific issues and/or a pre-submission meeting by writing to email@example.com. 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.
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 adopts a Commission Regulation confirming the classification of the substance. 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 to Commission Regulation (EU) No 37/2010 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 to Commission Regulation (EU) No 37/2010. 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 information on MRL assessments as follows:
- 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.
Certain substances used in veterinary medicines for use in food producing animals or in biocidal products for use in animal husbandry fall outside the scope of the MRL Regulation. They are listed in the document below:
- 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
If a company considers that a component of their product is not pharmacologically active, they can submit a request to have the substance included in the list above. Requests should be submitted to the CVMP following the guideline below:
- Guideline on data to be provided in support of a request to include a substance in the list of substances considered as not falling within the scope of Regulation (EC) No 470/2009