‘Controls on Animal Medicines’

Briefing Document No. 19

How does an animal medicine get to the market?

Before an animal medicine can be sold in the UK it must be approved. This takes the form of a marketing authorisation. The UK has one of the most stringent licensing systems for the authorisation of animal medicines in Europe, if not the world.

Development of a new animal medicine is very lengthy and expensive process. To develop a new product from scratch takes many years and costs millions of pounds.

Once a potentially useful compound has been identified, amongst other things

l studies have to be done into its pharmacology and modes of action

l studies are carried out into its potential toxicity (both acute and long term: to the animal, the person who will adminster the medicine, the consumer of any produce from a treated animal and the environment)

l analytical methods have to be developed to look for any residues left

l dose finding studies are carried out to find out at what dose the substance is effective in the appropriate species

l for farm animal medicines there has to be a Maximum Residue Limit for the active ingredient and residue depletion studies are needed to set withdrawal periods

l production methods have to be devised and scaled up to a commercial production line

l work is done on the formulation of the product

l stability tests are carried out

l field trials are run to test the product in real life

To apply for the marketing authorisation needed to sell an animal medicine, the company has to put together a very extensive dossier of information, which must follow a pre-determined format to set out in European law - even the guidance on how to set out the dossier runs to 184 pages! This information helps the Licensing Authority to carry out an independent scientific assessment of a product's safety, quality and efficacy.

So who does the approving?

There are three routes for obtaining marketing authorisations:

* the National procedure under which applications with supporting data are submitted to the Veterinary Medicines Directorate (VMD), a part of the Department Environment, Food & Rural Affairs. Marketing authorisations granted under this procedure are valid in the UK only. Only products that are not already authorised anywhere in the EU are eligible for the national procedure.

* the Decentralised procedure under which a holder of a marketing authorisation issued by one member state may apply to one or more other member states to issue identical authorisations on the basis of "mutual recognition". If one of the member states concerned considers that the product as authorised constitutes a risk to animal or public health or to the environment it may refer the dossier to the EU Committee for Veterinary Medicinal Products (CVMP) for arbitration.

* the Centralised procedure which is obligatory for some high technology products and optional for some other products. An application is made to the European Medicines Evaluation Agency (EMEA). The authorisation, if subsequently granted, is issued by the European Commission and is valid in all member states.

How do we know an animal medicine is safe?

The Licensing Authority will only grant a marketing authorisation if the veterinarians, pharmacists, chemists, toxicologists and environmental experts, either at the VMD in the UK or EMEA for products seeking EU-wide approach, and their advisory committees of independent experts (the Veterinary Products Committee in the UK or CVMP in Europe), are fully satisfied.

To get the authorisation, it is necessary to prove that the product is safe, that it will work, and that it is of good quality.

Safety

The safety aspects make sure the medicine can be used safely without causing harm to the animal being treated, people giving the treatment, the environment and, in the case of farm animals, that it will be safe to eat the meat, milk, eggs or honey from animals treated.

For food-producing animals, studies are required to see how quickly residues of the medicine are eliminated from the animal. Maximum Residue Limits (MRLs) are established to set a maximum level of the substance(s) concerned that may remain in the animal without posing a risk to consumers of produce taken from it. Withdrawal periods (the time between administration of the medicine and slaughter or the taking of food produce, eg milk or eggs) are then set to ensure that any remaining residues are below the MRL. Huge safety margins are built into the system to ensure that consumers are not put at risk. (See NOAH's briefing document "MRLs and the Safety of Food from Animals").

Quality

Quality is very important to ensure that product safety is upheld. The quality assessment makes sure that all batches of a product meet the required standards. Studies of the product's stability are used to ensure that the product retains its full potency, efficacy and safety, even when it is stored for long periods.

Efficacy

All medicines must do what they claim to do when used as instructed on the label. Extensive tests are carried out in the laboratory, in disease challenge studies and in field trials, to make sure that the product will actually work in practical "real life" situations, against the specified disease in the named species of animal, at the dose rate, frequency and duration of treatment recommended, and by the route of administration specified.

Only when the Licensing Authority is satisfied on all three criteria does it issue a marketing authorisation, without which the company is not permitted to sell the product.

What happens once a product is on the market?

Checks do not end at product approval. Although the requirements to prove safety, quality and efficacy are very strict, there is a rigorous system to report any problems experienced with products once they are on the market. Companies are required by law to report to the VMD any side effects they are told about. Vets and other animal medicine users are also actively encouraged to report problems they encounter. This allows any potential problems to be quickly recognised and dealt with. (See NOAH's briefing document "Pharmacovigilance: Monitoring Suspected Adverse Reactions to Animal Medicines").

How is the distribution of animal medicines controlled?

Distribution of animal medicines in the UK is strictly controlled by a variety of legislation. Wholesalers are required to hold a licence appropriate to the type of products in which they are dealing. Manufacturers are required to hold a manufacturer's licence for the products they produce, and their premises are regularly inspected by the Medicines Control Agency, a part of the Department of Health. The inspectors check the premises are suitable for the production of safe, effective medicines of a consistently high quality, and that they are being manufactured in accordance with their marketing authorisations. Vets' and merchants' premises and pharmacies are all regularly inspected to ensure they meet the required standards.

All authorised animal medicines are allocated to one of the following distribution categories, which control their retail supply:

POM Prescription Only Medicines: These can only be supplied by veterinary surgeons for animals under their care, or dispensed from a pharmacy in accordance with a written prescription from a veterinary surgeon.

P Pharmacy List: These can only be supplied by veterinary surgeons in respect of animals under their care, or from a pharmacy under the supervision of a pharmacist.

PML Pharmacy and Merchants List: These products, as well as being available from vets and pharmacists as above, can also be supplied to keepers of animals by agricultural merchants whose premises are registered and where the sale is authorised by a suitably qualified person.

GSL General Sales List: These products are available for general sale from any outlet.

MFS - authorised medicated premixes which can be incorporated into animal feed only under the terms of a medicated feedingstuffs prescription signed by a veterinary surgeon for animals under his/her care.

MFSX - authorised anthelmintic premixes which are exempt from the requirement for a prescription.

How do we know there are no harmful residues of animal medicines in our food?

Use of animal medicines in farm animals is strictly controlled by European law and requires observance of the withdrawal period. This is the time which passes 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) falls below the MRL.

The withdrawal period is set out in the data sheet for the medicine in the instructions for use which are part of the product packaging. Farmers are required by law to record all uses of animal medicines; it is therefore straightforward to ensure withdrawal periods are observed.

Statistics back this up: in the UK farmers and vets have an excellent track record of observing the regulations - and measures are in place to ensure things to stay that way. As part of that effort, the VMD operates two complementary surveillance programmes for animal medicine residues to ensure that residues above the MRL do not occur and that prohibited or illegal drugs are not used. In the few cases where confirmatory analysis shows presence of unauthorised medicines or concentrations above the MRL, these are followed up. The State Veterinary Service investigates the farm, advises, inspects and if appropriate, prosecutes. The figures are published regularly and results are reassuring - in 2000, 99.86% of red meat samples collected by the VMD were free of detectable veterinary residues.