Controls on Animal Medicines
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:
- studies have to be done into its pharmacology and modes of action
- studies are carried out into its potential toxicity (both acute and long term: to the
animal, the person who will administer the medicine, the consumer of any produce from a
treated animal and the environment)
- analytical methods have to be developed to look for any residues left
- dose finding studies are carried out to find out at what dose the substance is effective
in the appropriate species
- 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
- production methods have to be devised and scaled up to a commercial production line
- work is done on the formulation of the product
- stability tests are carried out
- 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. This information helps the national or European regulators to
carry out an independent scientific assessment of a product's safety,
quality and efficacy.
So who does the approving?
There are four 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 for 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 and Mutual Recognition procedures
are very similar: 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 a
product is not yet authorised anywhere in the EU, an application may be
made simultaneously to several member states under the Decentralised
Procedure, with one of the member states (the “rapporteur”) taking the
lead on assessment of the dossier.
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, the dossier is referred to the EU Committee for Veterinary
Medicinal Products (CVMP) for “arbitration”, where a binding decision is
reached.
the Centralised procedure is obligatory for
some high technology products and optional for some other products. An
application is made to the European Medicines 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?
A marketing authorisation will only be granted 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 and
consistent 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 regulator 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 an
authorisation appropriate to the type of products in which they are dealing.
Manufacturers are required to hold a manufacturer's authorisation for the
products they produce, and their premises are regularly inspected – for
pharmaceuticals by the Medicines and Healthcare Products Regulatory Agency
(an executive agency of the Department of Health) or for vaccines by the
Veterinary Medicines Directorate. 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 a
specific distribution category, which
controls the route through which they can be sold.
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 and 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 Veterinary Residues Committee independently
scrutinises the surveillance for veterinary residues in the UK. They publish
their summary results in their Annual Report, with detailed figures on
www.vet-residues-committee.gov.uk. Results are reassuring. Of almost
40,000 analyses annually, only a handful (less than 0.2%) contain detectable
residues of authorised veterinary medicinal products at concentrations above
the relevant MRL, and the independent Committee concludes that these pose no
risk to consumers. |
