Legislative background
The EU Directive on veterinary medicines, and thus UK legislation, starts from the principle that all veterinary medicines must be authorized, and that use of an unauthorized medicine or use in an unauthorized way is an offence. This protects animals, users, consumers and the environment from the potentially serious effects of untested or poor quality medicines.

However, recognizing that there are circumstances where the benefits of treatment with unauthorized medicines outweigh the risks, the legislators have given veterinary surgeons a unique privilege by way of an exemption from the general rule. This privileged exemption is known as the prescribing cascade, or simply the cascade.

The authorization process assesses veterinary medicines against statutory criteria of safety, quality and efficacy when used in accordance with the manufacturer’s recommendations for use. The use of medicines in ways that have not been authorized may pose potential risks that the authorization process seeks to minimize. Where there is no suitable authorized veterinary medicine in the UK, there is still a need to balance risks and benefits within the freedoms granted to veterinary surgeons.

The cascade is a long-standing legal flexibility providing a rational balance between the legislative requirement for veterinary surgeons to prescribe and use authorized veterinary medicines where they are available, and the need for professional freedom to prescribe other medicines where they are not. It is intended to increase the range of medicines available for veterinary use.

The importance of using authorized medicines
Animal species may have many physiological differences from humans and from each other. As a result they may each react differently to medicines. The authorization system for veterinary medicines requires a medicine to have proven quality and effectiveness and, most importantly, safety for the animal, the user (veterinary surgeon, farmer, pet owner, etc.), the environment and, for food animals, the consumer of animal produce. This assurance has to be provided for each species and each indication on the label.

In addition, animal medicines containing the same active ingredient as human medicines may be formulated differently. For instance, the formulation needs to ensure that the medicine is properly absorbed through the gut (which is rather shorter in a cat than a human). Human medicine formulations may contain different excipients or have different bioavailability from veterinary medicines. Therefore, using a medicine which is not authorized for animals increases the risk of harm to the patient.

In addition, the cost of developing a medicine for animal use is high and can involve much research and many tests not carried out for human medicines.

The use of human medicines, in place of the equivalent authorized veterinary medicine, may sometimes use information produced by veterinary companies on dosage regimes or safety. Assuming that the data on the veterinary medicine is directly relevant to the human medicine is potentially hazardous.

Veterinary surgeons remain entirely responsible for the treatment of animals under their care; use of a medicine prescribed in accordance with the cascade should be capable of being supported by clear auditable clinical evidence to justify the veterinary surgeon’s decision.

Generics
It is important to address the potential confusion with the use of the word ‘generic’. Authorized veterinary generics exist legitimately and can be used by veterinary surgeons in the same way as other authorized animal medicines. However, human generic medicines that are similar to the authorized veterinary medicines may not be used unless there is no suitable veterinary medicine available.

The cascade provides a legal mechanism allowing veterinary surgeons to use their clinical judgement to prescribe a suitable medicine where no authorized veterinary medicine exists. Prescription and use by veterinary surgeons of human generic medicines where a suitable veterinary medicine is available is a criminal offence and contrary to the Royal College of Veterinary Surgeons (RCVS) Guide to Professional Conduct.

Compliance with the cascade
A medicine prescribed in accordance with the cascade may be administered by the prescribing veterinary surgeon or by a person acting under their direction. Responsibility for the prescription and use of the medicine remains with the prescribing veterinary surgeon.

If there is no medicine authorized in the UK for a specific condition, the veterinary surgeon responsible for treating the animal(s) may, in particular in order to avoid unacceptable suffering, treat the animal(s) in accordance with the following sequence:

1.  A veterinary medicine authorized in the UK for use in another animal species or for a different condition in the same species.
2.  If there is no such medicine, use either:
(a) A medicine authorized in the UK for human use
(b) A veterinary medicine from another Member State or country outside the EU in accordance with an import certificate from the Veterinary Medicines Directorate (VMD).
3.  If there is no such medicine, a medicine prepared extemporaneously by a veterinary surgeon, pharmacist or a person holding an appropriate manufacturer’s authorization.

If the patient is a food-producing animal, then additional conditions apply.

Treatment in exceptional circumstances
Although not formally forming part of the cascade, where the health situation so requires, and where there is no suitable medicine available either as an authorized UK medicine or under the cascade, a veterinary surgeon may treat an animal with a veterinary medicinal product (VMP) authorized in a country outside the EU, but only in accordance with a Special Treatment Certificate (STC) granted by the VMD.

Supply under the cascade
Medicines prescribed by a veterinary surgeon in accordance with the cascade may be supplied against a written prescription by another veterinary surgeon, a pharmacist or a suitably qualified person (SQP), provided the medicine is of a classification and for a species for which the supplier would normally be permitted to supply it. For instance, a POM-VPS medicine authorized for dogs and horses, but prescribed under the cascade for cats could be prescribed by a veterinary surgeon and supplied against a written prescription by an SQP, but only if that SQP were qualified to supply companion animal medicines. Only veterinary surgeons and pharmacists may supply POM-V medicines.

The other conditions of supply, including the labelling requirements must still be met.

Small Animal Exemption Scheme
A veterinary surgeon may choose to use a Small Animal Exemption Scheme (SAES) medicine at any time in accordance with the medicine’s recommended use, regardless of whether there is an authorized medicine available. Thus, the cascade neither compels nor prevents the use of an SAES medicine.

However, should the veterinary surgeon wish to use the SAES medicine in a different way than that recommended, because of a professional judgement that such a medicine could provide a safer or better option for treatment, then this would be considered to fall under the last of the cascade options.

Scope of the cascade
The cascade provisions apply ‘in particular to avoid unacceptable suffering.’

EU and UK legislation on the cascade does not allow the cost of the medicine to be taken into account when deciding which medicine to use. For example, it is not permissible to use a human medicine because it is cheaper. Any use of a human medicine instead of the authorized veterinary medicine has to be justified by the veterinary surgeon on clinical grounds alone.

However, the cascade may be invoked in other appropriate circumstances, such as where microbiological tests show that a particular strain of an organism has developed resistance to all medicines whose labels contain indications against it. In this situation, a veterinary surgeon may consider that no authorized treatment exists for that condition and would, of course, wish to prescribe a treatment that will be effective (taking account of the other provisions of the cascade).

Other examples given by the VMD are as follows:

• Dosage considerations – sometimes a veterinary surgeon may consider that the effective treatment of a particular condition in a particular animal requires a different dosage from the one that appears on the label of a medicine. In such circumstances recourse to the cascade may be appropriate and the next option would be to consider the merits of using that medicine at an ‘off-label’ dosage (another condition in the same species) or a different authorized veterinary medicine. If neither can be administered safely at the dosage required, the veterinary surgeon should consider further options under the cascade
• Individual characteristics – if a particular animal has characteristics, such as age, general condition or known sensitivity to a particular substance, which the veterinary surgeon judged to present unacceptable risks and to contraindicate the use of the authorized medicine, they could conclude that no authorized medicine existed for that condition in that animal and consider other treatments
• Chronic infections – if a condition persists following treatment with an authorized medicine, the veterinary surgeon may consider in a particular case that there is no authorized treatment for that particular condition and that further use of medicines containing similar substances is contraindicated. In such circumstances it would be legitimate to consider alternatives in accordance with the cascade
• Build-up of resistance – in relation to anthelmintics, current advice is that resistance is likely to be encouraged by the repeated use of a single medicine. This can be avoided, with beneficial consequences for the health and welfare of the treated animals, by the use of two or more medicines in rotation. If there is only a single medicine authorized for anthelmintic use in a particular species, the veterinary surgeon may consider that the condition cannot be controlled using only the authorized medicine and use it in rotation with another medicine selected according to the cascade
• Complex conditions – diagnosis is a matter for the veterinary surgeon under whose care an animal or animals have been placed. Some conditions can be viewed overall and treated accordingly. For instance, pneumonia may be regarded as a single condition. On the other hand, the diagnosis may be of more than one concurrent condition, such as pneumonia with fluid retention. In such circumstances the veterinary surgeon would need to exercise their professional skills to reach a diagnosis and prescribe the most effective treatment. If they consider that in the circumstances there are two or more concurrent conditions, the treatment of each would need to be considered in accordance with the Veterinary Medicines Regulations (VMR). However, due account of the usual factors, such as drug incompatibilities and side-effects, must be considered
• Unavailability of medicines – if a medicine cannot be obtained despite diligent search and in a reasonable time, the veterinary surgeon may conclude that in the circumstances it does not exist. In such circumstances the cascade should be followed to identify a suitable alternative. However, it is appreciated that there may be cases where urgency dictates that a veterinary surgeon uses whatever is to hand, whether authorized or not.

Suspected adverse reactions
If a veterinary surgeon concludes that an authorized medicine does not exist in a particular case because they suspect a lack of efficacy or the likelihood of unacceptable side-effects, all experiences of this kind involving veterinary medicines, whether authorized or unauthorized, should be reported as suspected adverse reactions to the VMD where they are recorded and monitored.

Import certificates
Where there is no suitable authorized medicine in the UK to treat a particular condition and when the health situation so requires, a veterinary surgeon may wish to seek an import certificate.

A VMP authorized in another EU Member State requires a special import certificate (SIC); a veterinary medicine without a full marketing authorization, or an authorized veterinary medicine from outside the EU, or a human medicine from outside the UK all require a STC.

Further information
Veterinary Medicines Directorate
Veterinary Medicines Guidance Note 7 – Import Certificate Schemes
Veterinary Medicines Guidance Note 14 – Marketing Authorisation Exemption Scheme for Pet Animal Medicines
Veterinary Medicines Guidance Note 15 – Controls on the Administration of Veterinary Medicines