The clinical needs of patients can usually be met by prescribing and administering a licensed medicine. There will be cases where a medicine cannot be used because the patient is unable to take it in its licensed form. In such situations, nurses may be able to arrange for the patient to be supplied with an unlicensed medicine to specifically meet that patient's special need (Human Medicines Regulations 2012, regulation 167).
The Human Medicines Regulations 2012 generally require that medicinal products for human use are supplied and administered in accordance with a product licence or marketing authorisation. This licence is granted following satisfactory completion of rigorous laboratory and clinical trials that test the safety quality and efficacy of a medicinal product (Council Directive 2001/83/EC). The marketing authorisation reassures nurses and their patients that even though there are likely to be some common adverse drug reactions, used properly, the medicine is safe and effective. It also provides the prescriber with a defence in that inherent harm from the product will be attributed to the producer under the Consumer protection Act 1987 and the Product Liability Directive (Council Directive (EEC) 85/374 1985). In Les Laboratoires Leo SA v Scovazzo [1999], a pharmaceutical company was found liable under product liability law when a medicine that had been developed with a digestible sponge coating caused gastric bleeding. Nurses are, therefore, required to administer licensed medicines that have been subject to rigorous scrutiny for safety, quality and efficacy where they meet the clinical need of the patient (Medicines and Healthcare products Regulatory Agency (MHRA), 2014)
Use of unlicensed medicines
The EU recognises that some patients' clinical need for medicines cannot be met by the current range of licensed medicines, or that it is simply not commercially viable for a pharmaceutical company to bring a medicine to market if its uptake would be relatively low—as is often the case with liquid medicines. In those cases, the EU (Council Directive 2001/83/EC) allows Member States, including the UK, to put in place arrangements for an authorised health professional to commission the manufacture of an unlicensed medicinal product to meet the special needs of an individual patient under their direct personal responsibility. The UK has made use of this derogation to establish arrangements for the manufacture and supply of such unlicensed medicines that are commonly known as specials.
Article 5(1) of Directive 2001/83 provides:
‘A Member State may, in accordance with legislation in force and to fulfil special needs, exclude from the provisions of this Directive medicinal products supplied in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised health-care professional and for use by an individual patient under his direct personal responsibility.’
Off-label use
Directive 2001/83 makes clear that an unlicensed medicine or special must only be supplied and administered if it necessary to meet the special need of a patient. Licensed medicines must be prescribed and administered where they can meet the patient's need, even if the use of the medicine is outside its licence terms. This is known as using the licensed medicine off-label. The licensed antidepressant amitriptyline, for example, is commonly used off-label to treat severe abdominal pain in irritable bowel syndrome (Frost et al, 2011).
The use of specials under the Human Medicines Regulations 2012
In the UK, the supply and administration of unlicensed specials is lawful under the Human Medicines Regulations 2012, regulation 167 where it is:
To ensure that specials are used only to meet a specific clinical need of a particular patient, the MHRA, which polices medicines law in the UK, requires manufacturers to obtain written evidence of the special need that must be kept for inspection (MHRA, 2014). A special need must be a clinical need, such as an intolerance or allergy to an ingredient in a licensed medicine or an inability to swallow solid forms of oral medicines (eg tablets or capsules).
The decision on whether or not a special is needed must not be based on cost, convenience or operational need. In European Commission v Republic of Poland (C-185/10) [2012], an exemption allowing the use of cheaper unlicensed medicines in preference to licensed medicines in Polish law was declared in breach of the European Directive by the European Court of Justice and had to be repealed.
Manufacture
The Human Medicines Regulations 2012, regulation 8 defines manufacture in relation to a medicinal product as:
‘Any process carried out in the course of making the product, but does not include dissolving or dispersing the product in, or diluting or mixing it with, some other substance used as a vehicle for the purpose of administering it.’
This definition limits manufacture to the actual creation of a product. It allows pharmacists to crush a tablet or open a capsule to mix it with a solution to make it easier for the patient to take. It also allows nurses to mix substances, such as antibiotics or other medicines in powder form, with water for injection before administration.
The manufacture of a special involves creating a product that meets the special clinical need of the patient and therefore requires a manufacturer's special licence. The licensing process ensures that the manufacturing site and operation are subject to inspection and that the medicine that is produced meets the specification of the prescriber.
A special cannot be advertised and may not be supplied if an equivalent licensed product is available that could meet the patient's needs. Records detailing the use of specials must be kept, and serious adverse drug reactions reported to the MHRA. Responsibility for deciding whether an individual patient has special needs that a licensed product cannot meet should be a matter for the health professional responsible for the patient's care (MHRA, 2014).
Independent prescribers and specials
Independent nurse prescribers can issue a prescription for an unlicensed medicine. The authority was initially granted under the Medicines (Exemptions And Miscellaneous Amendments) Order 2009 and continued by the Human Medicines Regulations 2012, article 167.
To ensure a higher degree of quality control of the unlicensed medicines, independent prescribers generally issue a prescription for a pharmacy to prepare, or obtain a special from a licensed specials manufacturer. Independent prescribers who prescribe specials do so on their own responsibility. Liability for harm caused to a patient by an unlicensed medicine would be decided in negligence law (Richardson v Miller [2000]).
Cost of unlicensed medicines
As unlicensed medicines are not produced in commercial quantities, their cost can be considerably higher than products that are licensed. The Human Medicines Regulations 2012 prohibit the advertising of special medicinal products and that also leads to a lack of transparency in the pricing of specials.
In response to the lack of transparency, revised arrangements for the reimbursement of community pharmacists for specials were introduced in 2009 (Department of Health, 2011). The revisions place some of the most commonly used specials onto the drug tariff, which is the list of agreed prices for medicines used in the NHS. The aim is to improve transparency and link the cost of reimbursement to pharmacies to the actual cost of the product.
Only some 57 specials are currently part of the drug tariff and it appears some distributors and manufacturers of specials continue to offer pharmacists incentives for sourcing products from their company at a higher cost to the NHS. The practice is not recorded so it is difficult to ascertain how widespread it is (Bryant, 2013).
Even though the Nursing and Midwifery Council (NMC) and the MHRA argue that it is for the prescriber to decide if a particular patient has a medical need that can only be met by a special, it is likely that due to cost clinical commissioning groups (CCGs), NHS Trusts and Health Boards will have local policies on the supply of specials to keep costs down. However, the Health Service Ombudsman found that a GP practice that removed a patient from its list because of the cost of the liquid special medicines he required had acted unlawfully and contrary to the patient's best interests as it put him at risk (Parliamentary and Health Service Ombudsman, 2013)
Conclusion
Nurses who have a patient whose clinical need cannot be met by a licensed or off-label medicine can ask for that clinical need to be met by an unlicensed special medicinal product.
Even though the MHRA and NMC state that it is for the health professional to decide if a patient's needs can only be met by an unlicensed medicine, employers are likely to limit their use on the grounds of cost.
Nurses must be clear what their patient's special clinical need is and why that need cannot be met by a licensed or off-label medicine.