Although veterinary medicines are absolutely necessary to ensure animal health and welfare, their use in animals for food may leave residues in food products obtained from treated animals.

Starting from this situation, and in order to protect consumer health, it is equally essential to make an assessment of the safety of these substances taking into account toxicological hazard, environmental pollution, and the undesirable pharmacological and/or microbiological effects form any residue.

Thus, a substance that is pharmacologically active can be used in animals for food if it has undergone a risk assessment, based on solid scientific fact and a favourable result. Maximum Residue Limits (MRL) for this substance must be established when considered necessary for the protection of human health.

Definitions:

• Veterinary medicine residue: "All pharmacologically active substances, whether active principles, excipients or degradation products, and their metabolites which remain in foodstuffs obtained from animals to which their veterinary medicinal product in question has been administered".
• Maximum Residue Limit: "the concentration of residue resulting from the use of a veterinary medicinal product legally permitted in the EU and considered admissible from the point of view of consumer safety of a food product".

These MRLs are set according to their toxicological characteristics based on their use according to codes of good veterinary practice, resulting from residue depletion tests, etc. In turn, they serve as a reference to determine the waiting time for permitting the sale of medicaments, which means the time elapsing between administering the drug and slaughtering the animal.

AESAN is working in this field as a member of the:

• Committee for the evaluation of medicaments for veterinary use of the Spanish Agency for Medicaments and Health Products (AEMPS), and
• Committee on the availability of veterinary medicaments of AEMPS.
• Committee of the Codex Alimentarius (FAO/WHO) on residues of veterinary medicaments in foodstuffs.

The current basic rule including and regulating these MRLs is Regulation (EC) No 470/2009 of the European Parliament and of the Council of 6 May 2009, laying down Community procedures for the establishment of residue limits (MRL) of pharmacologically active substances in foodstuffs of animal origin repealing Council Regulation (EEC) No 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council, and Regulation (EC) No 726/2004 of the European Parliament and of the Council.

This regulation has two basic objectives:

1. To protect human and animal health, and therefore lays down the following:

• A pharmacologically active substance can only be used in animals producing food (meat, fish, milk, eggs and honey) if it has received a favourable assessment from the EMA (European Medicines Agency). The scientific risk assessment must take into account the metabolism and elimination of the active substances, the type of residues and the ADI (Acceptable Daily Intake) Therefore, it must be emphasised that the new item in the regulation forces the dictate of the EMA to take into account all scientific discoveries relevant to EFSA (European Food Safety Authority).
• As a result of the above, active substances are classified and the therapeutic categories to which they belong, stating: and MRL, a provisional MRL, no need to set an MRL, or prohibiting the use of the substance.

2. To ensure the availability of appropriate veterinary medicaments for diseases affecting animals for food, with the proposal of the following:

• To establish a procedure from extrapolated MRL already set fro an active substance in a food/species to other derivations of foodstuffs or different animal species.
• To incorporate, without a prior dictate from the EMA, those MRL adopted by a Decision of the Codex Alimentarius (CLXs), to which the EU delegation has not expressed an objection.

As an extra to the objectives, and to facilitate control of the presence of pharmacologically active substances in foodstuffs which have not been classified in the EU, this rule has also laid down a procedure to establish benchmarking values in the concentration of residues or "benchmarking values for intervention purposes", which means the lowest concentration of a residue that can be detected and confirmed by an official testing laboratory. In practice, it explains that concentrations below this benchmarking value set for an unauthorised substance must not contravene EU law. This concept had previously been expressed, to some extent, through the Minimum Required Performance Limits (MRPL).

In addition, it must be pointed out that, although this Regulation (EC) No 470/2009 repeals Regulation (EC) No 2377/1990, still has to publish a new regulation containing the set MRLs in its annexes I to IV, so these remain in force until then.

Especially important among the annexes in Regulation 2377/1990 is the list of pharmacologically active substances for which no maximum limit can be set that is safe for the consumer, so that their use in animals for food is prohibited.

To complement regulation (EC) No 470/2009 of 20 January 2010, Regulation (EU) No 37/2010 has been published containing the information in the annexes of Regulation 2377/1990, now repealed, i.e. the maximum residue limits (MRLs) of pharmacologically active substances in food of animal origin. Various new items are also included, such as:

1. Only two lists are drawn up instead of the four former annexes: MRLs of permitted substances, and a list of prohibited substances.
2. Information on the therapeutic classification of the substances, plus any conditions or restrictions on its use.
3. They are in alphabetical order.

The list of pharmacologically active substances for which no maximum limit can be set that is safe for the consumer, so that their use in animals for food is prohibited includes:

• Aristolochia spp. and it formulations
• Chloramphenicol
• Chloroform
• Chlorpromazine
• Colchicine
• Dapsone
• Dimetridazole
• Metronidazole
• Nitrofurans (including furazolidone)
• Ronidazole

The regulation on MRL for pharmacologically active substances also includes MRL in food of additives used in permitted animal feed based on Regulation (EC) No 1831/2003, provided, as always, that EFSA gives a favourable assessment. However, it should be pointed out that the Ministry for the Rural and Marine Environment is the competent authority for matters relating to animal food.

Some useful links for consulting MRLs are:

http://ec.europa.eu/enterprise/pharmaceuticals/mrl/regindex.htm (DG ENTERPRISE AND INDUSTRY)

http://www.emea.europa.eu/htms/vet/mrls/background.htm (EUROPEAN MEDICINES AGENCY)

http://www.codexalimentarius.net/mrls/vetdrµgs/jsp/vetd_q-e.jsp (CLXS. CODEX ALIMENTARIUS)

Download Regulation (EC) No 470/2009  pdf

A particular case in setting MRLs for pharmacologically active substances in foodstuffs is the presence of coccidiostats and histomonostats in food products as a consequence of the technologically unavoidable transfer of additives in fed of species for they are not authorised ("cross contamination" or "unavoidable transfer").

The European food Safety Authority (EFSA) has issued various opinions on the risks involved by their presence for animal health and human health, based on hypothetical transfer indices of 2%, 5% and 10% of feed produced with the maximum permitted level of coccidiostats or histomonostats in feed manufactured at a later stage, for which these substances are not intended.

The result of these assessments was approved (together with a Directive to regulate the maximum levels in feed) in Regulation (EC) No 124/2009 of the Commission of 10 February 2009, setting the maximum levels of coccidiostats or histomonostats in food resulting from the unavoidable carry-over of these substances in non-target feed. This regulation is based on Council Regulation (EC) No 315/93 of 8 February 1993, laying down Community procedures relating to pollutants present in food products intended for human consumption.

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