Legal background
The ‘‘Animals, Meat and Meat Products (Examination for Residues and Maximum Residue Limits) Regulations 2015’’ (as amended) control residues of animal medicines in food producing animals. The Regulations make it an offence ‘to sell or supply for slaughter any animal for human consumption, if the withdrawal period in respect of any animal medicine which has been administered to the animal has not expired’. The legislation is applied to the animal keeper, but any person who supplies animal medicines is liable to claims for meat losses, fines or penalties if incorrect withdrawal periods are advised.
To summarise, the Regulations, in relation to the use of animal medicines:
prohibit the sale, possession or administration to animals of specified unauthorised substances
prohibit the possession, slaughter or processing of the meat of animals intended for human consumption which contain or have been administered with specified unauthorised substances
prohibit the sale or supply for slaughter of animals if the appropriate withdrawal period has not expired and prohibit the supply for slaughter or, subject to exceptions, the sale of animals or animal products which contain unauthorised substances or an excess of authorised substances
prohibit, subject to exception, the disposal for human or animal consumption of slaughtered animals containing specific unauthorised substances
empower authorised officials to inspect and examine animals and to take samples and provide for the analysis of official samples
provide for offences and penalties and for enforcement by each enforcement authority specify requirements relating to keeping records of administration of animal medicines
In addition, under the Veterinary Medicines Regulations it is an offence to administer any animal medicine to an animal unless that product has a marketing authorisation authorising its administration in the UK and the administration is in accordance with that marketing authorisation. However, in cases where no authorised product exists for a condition in a particular species, and in order to prevent unnecessary suffering, a veterinarian may prescribe certain other products in accordance with the conditions of the prescribing ‘cascade’, set out in Schedule 4 of the Veterinary Medicines Regulations. For food-producing animals treated under the provisions of the cascade, there is a requirement that only medicines whose ingredients have been assessed for residues safety can be used, and specified records must be kept by the veterinarian and the farmer.
Further details of the requirements of both sets of Regulations, are available from the Veterinary Medicines Directorate, Woodham Lane, New Haw, Addlestone, Surrey KT15 3LS. Telephone No: 01932 336911.
Those selling animal medicines should take every opportunity to remind their clients about their responsibilities under these Regulations and also impress upon them that the Regulations require the use of all administered medicines to be recorded.
NOAH (in conjunction with the Animal Health Distributors Association, AHDA) has produced a record book to enable farmers to meet their responsibilities for record keeping. Copies of the record book are available from AHDA (telephone 01664 822335).
Maximum Residue Limits (MRLs) of Animal Medicines in Food Derived from Animals
Among the responsibilities of those involved in producing food from animals is the need to protect consumers from residues of animal medicines which could otherwise remain in that food.
Residues raise two issues:
toxicity for humans
technical problems for the food product processing industries
Veterinary surgeons and farmers who prescribe and use veterinary medicines in food animals are subject to extremely important European regulations to keep harmful residues out of the food chain. These regulations set very strict terms for the producers and users of animal medicines for use in food animals.
EU Directive 2001/82 & Regulation 37/2010
EU Directive 2001/82 allows for the use of some medicines outside of their authorisation. This applies where there is no authorised medicine available to treat a particular disease or condition in an animal. This is known as the cascade.
Only sustances in Table 1 of Regulation 37/2010 may be used in food producing animals under the cascade.Substances in Table 2 of Regulation 37/2010 must never be used in food producing animals.
Definitions
- Residues of animal medicines (except for biologically active constituents):
These are pharmacologically active substances (whether active principles, excipients or degradation products) and their metabolites, which remain in foodstuffs obtained from animals that have been administered the animal medicine in question.
Maximum Residue Limit (MRL):
Maximum concentration of residue resulting from administration of a animal medicine which is legally permitted in the Community or recognised as acceptable in or on a food.
Withdrawal period:
The time between the last dose given to the animal and the time when the level of residues in the tissues (muscle, liver, kidney, skin/fat) or products (milk, eggs, honey) is lower than or equal to the MRL.
Procedure for the evaluation and determination of MRLs
MRLs are determined by the Committee for Veterinary Medicinal Products (CVMP) of the European Medicines Agency (EMA). Manufacturers apply to the Agency for an MRL, supplying them with all the information the Committee needs to make their assessment.
The MRL must be set at European level for all active pharmacological substances.
Establishing an MRL for a substance included in a veterinary medicine
This is based on the safety and residues dossiers produced by manufacturers:
(a) Safety Dossier:
This dossier contains all of the pharmacodynamic, kinetic, metabolic and toxicity studies carried out with the substance in the laboratory.
It includes an Acceptable Daily Intake (ADI) for humans of the residues of the substance under assessment. ADI is a measure of the amount of a specific substance (in this case the residue of a veterinary medicine) in food that can be ingested (orally) on a daily basis over a lifetime without an appreciable health risk.
The ADI is assessed on the basis of experimental studies and determination of a No Observable Effect Level (NOEL) - the dose with no observable effect in the species in the most sensitive test.
This can be:
either the toxic NOEL (majority of substances)
or the pharmacological NOEL for certain substances (anti-inflammatory, neurolpetic...)
or the micro-biological NOEL (on the gastro-intestinal flora of man for the anti-infectives)
by applying a safety factor of between 1 00 and 1 000 in order to extrapolate from animal to man.
Description: NOEL_equation
Assuming an average weight of 60 kg for man,
Total ADI=ADI x 60
(b) Residue Dossier:
This dossier contains all of the data relating to kinetics, metabolism and residues of the substance.
It allows determination of MRLs for foodstuffs derived from the treated animal by distributing the total ADIs among these foodstuffs according to the residues distribution among these tissues in the treated animal.
Normally MRLs are set for four tissues: muscle, liver, kidney and fat (or, in the case of pigs and poultry, skin and fat in natural proportions), and also milk and eggs where appropriate.
Member States are responsible for the establishment of a withdrawal period for the medicinal product on the basis of these MRLs. The withdrawal period is calculated from the depletion curves of the residues in the target tissues in the relevant species.
The 2 Tables:
After evaluation, a pharmacologically active substance is allocated to one of two tables:
Table 1 -Allowed substance for use in food producing animals.
Table 2 - Prohibited substance from use in food producing animals.
Conclusion
A withdrawal period for a veterinary medicine can only be achieved after considerable research. It is there for a purpose: to ensure consumer safety. Farmers and veterinarians who do not respect withdrawal periods or misuse substances that they are handling are breaching their responsibility as partners in the food chain.