- The legal provisions for ‘cascade use’ exist to allow prescribing
veterinary surgeons to ensure animal health and welfare where authorized
veterinary medicines are not available
- Where authorized veterinary medicinal products (VMPs) exist for the
treatment of a condition, prescribing veterinary surgeons should use
these products first
- The veterinary medicines industry is far smaller than the human
medicines sector. For this reason, it is not possible for the animal
medicines industry to develop products for the treatment of all
conditions affecting all species that veterinary surgeons are required
- Suspected adverse reactions involving cascade use of products should be
reported to the regulatory agency, the Veterinary Medicines Directorate
- Where VMPs are being used under the cascade, written consent should be received from the animal owner(s)
The cascade is a long-standing legal flexibility providing a rational balance between the legislative requirement for veterinary surgeons to prescribe and use authorized VMPs where they are available, and the need to prescribe other medicines where they are not. It is intended to increase the range of medicines available for veterinary use, in order to avoid unacceptable suffering.
The European Union Veterinary Medicines Directive (2001/82) is the basis of veterinary medicines regulation throughout all EU Member States. National laws, such as the UK Veterinary Medicines Regulations (VMR) are heavily based on the EU law. The EU Veterinary Medicines Directive is currently under review. It is expected that a new VMR will come into effect across the EU in late 2017 or early 2018.
The current law starts from the principle that all VMPs must be authorized, and that use of an unauthorized medicine, or use of an authorized medicine 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 VMPs.
However, the law recognizes that there are circumstances where the benefits of treatment of animals with unauthorized medicines outweigh the risks, particularly where there are no veterinary authorized medicines for a condition or for a species, especially for species that are not usually in captivity. As a result, the legislators have given veterinary surgeons a unique privilege by way of an exemption from the legal requirement to use an authorized VMP. This privileged exemption is known as the 'prescribing cascade', or simply ‘the cascade’, and it exists to ensure animal health and welfare needs are met.
The veterinary medicines industry globally is worth approximately 2% of the human medicines industry. As a result, it is not possible for veterinary medicines companies to develop authorized medicines for each and every condition of a wide variety of species. This is particularly the case for so-called ‘minor use, minor species’ medicines. Companies simply will not obtain a return on investment and the financial incentives to develop products for all conditions in all species are not there.
The importance of using authorized medicines
Individual animal species have physiological differences from humans and from each other, which may affect the way the animal responds when it is treated. The authorization system for VMPs requires each to have proven quality and effectiveness and most importantly safety for the animal, the user (veterinary surgeon, farmer, pet owner), the environment and, for food animals, the consumer of food from animals. This assurance has to be provided for each species and each indication on the VMP’s summary of product characteristics (SPC), a legal document which is approved by the regulatory agency. The authorization process requires independent regulators to carry out an assessment of VMP licence applications against criteria of safety, quality and efficacy when used in accordance with the manufacturer’s recommendations.
In addition, animal medicines containing the same active ingredient as human medicines may be formulated differently. For example, for orally administered products, the formulation needs to ensure that the medicine is properly absorbed through the gut, a process which differs between animal species and between animals and people. Human medicine formulations may contain different excipients or have different bioavailability from VMPs. Therefore, using a medicine which is not authorized for animals increases the risk of treatment failure or harm to the treated animal.
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 supported by clear auditable clinical evidence to justify the veterinary surgeon’s decision.
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 VMPs. A generic is essentially a ‘copy’ of the pioneer or originally developed product. After the original product’s data protection period has expired, other companies may produce generics of the product. Generic veterinary medicines undergo the usual assessment for safety, quality and efficacy. A generic VMP is of course considered to be a fully authorized VMP, in the same way as the ‘pioneer’ product.
However, human medicines, including human generic medicines that contain a similar active ingredient to the authorized veterinary medicines, may not be used unless there is no suitable veterinary medicine available.
Compliance with the cascade – how does it work in practice?
Prescription and use by veterinary surgeons of human medicines, where a suitable veterinary medicine is available, is an offence under the VMR and is also contrary to the Royal College of Veterinary Surgeons (RCVS) Code of Professional Conduct.
However, as outlined above, to avoid unacceptable suffering there are occasions when the prescribing veterinary surgeon can justifiably prescribe under the cascade. Responsibility for the prescription and use of the medicine remains with the prescribing veterinary surgeon.
The legal basis for the cascade is as follows:
If there is no authorized VMP available in the UK for the condition, the veterinary surgeon responsible may treat the animal with the following, in this ‘cascaded’ order (See the Veterinary Medicines Regulations 2013 Schedule 4):
- a. A VMP authorized in the UK for use with another animal species for that condition, or another condition for that animal species.
- b. If there is no such medicine:
- i. An authorized human medicine; or
- ii. A VMP not authorized in the UK, but authorized in another EU member state for use with any animal species (if the animal in question is a food-producing animal, this must be a food-producing species)
- c. If there is no such medicine, a VMP prepared extemporaneously by a pharmacist, veterinary surgeon or person holding a manufacturing authorization for that type of product (often referred to as ‘veterinary specials’).
Supply under the cascade
Only veterinary surgeons are permitted to prescribe under the cascade. However, a ‘suitably qualified person’ (SQP), a veterinary nurse or indeed any member of the practice staff can supply any medicine when acting under the direction of a veterinary surgeon. The responsibility for ensuring that such a person carries out the task correctly remains with the veterinary surgeon.
Medicines prescribed by a veterinary surgeon in accordance with the cascade may also be supplied against a written prescription by other legal retailers of veterinary medicines (another veterinary surgeon, a pharmacist or an SQP), provided the medicine is of a classification and for a species for which the supplier would normally be legally permitted to supply it.
Exemption for small pet animals
A veterinary surgeon may choose to use an exemption for small pet animals (ESPA) 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 ESPA medicine.
However, should the veterinary surgeon wish to use the ESPA medicine in a different way than that specified on the label 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’. The 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. Every case will be examined on its merits.
Some examples given by the VMD to provide guidance on how the cascade should work in practice can be found on the VMD webpage, The Cascade: Prescribing unauthorised medicines (formerly VMGN Number 13).
Suspected adverse events
If a veterinary surgeon concludes that an authorized VMP 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 use or unauthorized use, should be reported as suspected adverse events to the VMD and the marketing authorization holder, where they are recorded and monitored as part of the VMD’s Suspected Adverse Event Surveillance Scheme.
Where there is no suitable authorized medicine in the UK to treat a particular condition and when the situation so requires, a veterinary surgeon may wish to seek an import certificate.
A product authorized in another EU Member State requires a Special Import Certificate (SIC), which must be obtained from the VMD. An authorized veterinary medicine from outside the EU or human medicines from outside the UK all require a Special Treatment Certificate (STC), which must also be obtained from the VMD.
Labelling of medicines prescribed under the cascade
The following information must be included on labels for products administered under the cascade. Where the product is supplied in its original packaging and already includes some of this information which remains legible following application of the dispensing label, it is not necessary to repeat this information on the dispensing label. If it is not feasible to include all of the information on the label due to the size of the packaging, it must be included on a separate sheet. The information provided must include:
- Name and address of the pharmacy, surgery or approved premises supplying the product
- Name of the veterinary surgeon who has prescribed the product
- Name and address of the animal owner
- Identification (including species) of the animal or group of animals
- Date of supply
- Expiry date of the product, if applicable
- Name or description of the product, which should include at least the name and quantity of the active ingredient
- Any special storage precautions
- Any necessary warnings for the user, target species, administration or disposal of the product
- Withdrawal period, if relevant
- 'Keep out of reach of children’ and ‘For animal treatment only’.
There are specific record-keeping requirements for veterinary surgeons who administer or supply medicines to be dispensed under the cascade. These are set out below and must be retained for at least 5 years and be made available on request to a duly authorized person:
- Date of examination
- Animal owner’s name and address
- Identification and number of animals treated
- Result of the veterinary surgeon’s clinical assessment
- Trade name of the product(s) prescribed
- Batch number
- Name and quantity of the active substance
- Doses administered
- Duration of treatment
- Withdrawal period.
If the client or other records already have this information, no additional separate records are needed as long as the information is accessible on request. Veterinary surgeons may also find it helpful to include information identifying treated animals among their records.
Informed consent before treatment of animals
It is not a legal requirement under the VMR to obtain informed consent from the owner of an animal to be treated under the cascade. This requirement is part of the RCVS Code of Professional Conduct, which states the following: ‘A decision to use a medicine which is not authorised for the condition in the species being treated where one is available should not be taken lightly or without justification. In such cases clients should be made aware of the intended use of unauthorised medicines and given a clear indication of potential side effects. Their consent should be obtained in writing. In the case of exotic species, most of the medicines used are unlikely to be authorised for use in the UK and owners should be made aware of, and consent to, this from the outset.’
Veterinary Medicines Directorate
Apply to change a marketing authorisation for a veterinary medicine (formerly VMGN Number 2 – Marketing Authorization for Veterinary Medicinal Products)
Apply for a certificate to import a Veterinary Medicine into the UK (formerly VMGN Number 5 – Import Certificate Schemes)
Exemption from authorisation for medicines for small pet animals (formerly VMGN Number 12 – Exemption Scheme for Small Pet Animals VMGN Number 13 – Guidance on the use of the cascade)
VMD statement – Responsible antibiotic use under the cascade