Unlicensed Medicines are known to be manufactured without any market authorisation (MA). In other words, unlicensed medicines are those prescribed products that do not hold an MA and are prepared on an individual basis by ‘special order’ manufacturers (for example liquid preparations), products classed as ‘food supplements’ (such as vitamin D preparations), and medicines that are licensed abroad but which do not hold a UK MA.
Here are a few things that you need to know about unlicensed medicines, their usages and more. Read on.
What is an MA?
An MA or product licence is granted by Medicines and Healthcare products Regulatory Agency (MHRA) and has been proven entirely safe and effective.
When should one use unlicensed medicines?
As per MHRA and General Medical Council, unlicensed medicines should only be used when existing licensed medicinal products are not appropriate to meet patient needs.
The best example of this case is often seen in paediatric medicines. Here, standard solid oral dosage forms are difficult to be used due to smaller or unusual doses. Patients who face difficulty in swallowing solid oral dosage forms and those who need medicines through enteral feeding tubes also fall under the same category.
Apart from the UK, medicines that have received marketing authorisations in other countries are another example of unlicensed medicines that may be employed where licensed preparations have been unsuccessful or unsuitable. For example, Midodrine tablets that are licensed in the US but not in the UK may be used for the treatment of orthostatic hypotension where treatment with fludrocortisone has been unsuccessful, or use of a steroid is unsuitable for the patient. There is also significant prescribing of products classed as ‘food supplements’ that do not hold a marketing authorisation.
Important guidelines on Unlicensed Medicines:
A product licence covers the majority of medicines sold or supplied against a prescription. However, some of these are exception.
- These include medicines prepared by a manufacturer but not on sale in the country. There are chances that these medicines may be awaiting the grant of a UK product license, be undergoing clinical trial, be manufactured for export or may have been withdrawn from the UK market. It is usually possible to obtain supplies of these medicines from the manufacturer, or through a specialist importer. Since the medicines are not licensed, the prescriber holds responsibility for their use along with liability for any consequences.
- Pharmacists are advised to ensure that the prescriber is aware of written notification and that the prescriber should duly sign it.
- Individual Patient Basis: Individual Patient Basis is applied when the medicine has to be used for the treatment of a particular patient. It may usually be obtained from the manufacturer. It should be noted that the manufacturer has no justification for demanding individual patients’ names, and hospitals divulging such information may be breaking patient’s confidentiality. The hospital is however advised to keep detailed records of the purchase and administration.
- Medicines prepared for a specified patient as per a prescriber’s instructions: This broadly includes all kind of dispensing, including TPN compounding, IV additives and cytotoxic reconstitution services. As per a Section 10 exemption, pharmacies are exempted from the need to hold a manufacturer’s license, as long as medicines are prepared by or under the supervision of a pharmacist as per the practitioner’s prescription. The products would not generally be labelled with a ML or PL number.
- Manufacturer’s Specials License: This refers to unlicensed medicines obtained from a hospital or a commercial supplier. Such medicines can be supplied against an order or prescription by a hospital manufacturing unit or commercial manufacturer holding the above said license. Specials will be labelled with the manufacturer’s license (ML) number. The manufacturer of specials cannot advertise any product by name nor publish a catalogue or price list. He/she is allowed to advertise his/her service but not ask for orders.
- Altered products: As the name suggests, altered products refer to medicines in which the formulation/combination has been altered. This might happen in cases where a patient finds difficulty in swallowing tablets. The medicines may be undertaken by crushing tablets or opening capsules or by a pharmacist as extemporaneous dispensing or by the medicines administrator.
- Re-packed medicines: The product license is also regulated on packing of medicines. When a medicine is removed from its original container and re-packed, either during a dispensing operation or for small packages, it becomes an unlicensed product. Here, the medicine is already manufactured and is sold in accordance with a product license. So, re-packed medicines are of little significance to prescribers and MHRA guidelines may not apply to them.
Ways through which the operations of licensed medicines can be carried out
- In-house on a small scale
- From a packaging unit holding a manufacturer’s specials license, which covers assembly activities or a manufacturer’s (assembly) license.
What are the implications for prescribers on prescribing unlicensed medicines?
Prescribing and dispensing of unlicensed medicines is a responsible task for both the prescriber and the pharmacist. Since an MA holder is hesitant to take responsibility for any complications occurred during the use of unlicensed medicines, the liability rests with the prescriber. Nevertheless, the pharmacist decides the source of the medicine and a prescriber is usually not aware of it. The pharmacist, on the other hand, is unaware of why an unlicensed preparation is prescribed to a patient. Sometimes, secondary care consultants also prescribe such medicines but they are always advised to follow general protocols and information.
The formulation and packaging of unlicensed medicines involves no clinical trial data. Hence, there are no demonstration of safety and efficacy of the formulation and no studies to support a clear expiry date. As a result, unlicensed medicines come with a recommended expiry and storage conditions based on the experience of their manufacturers.
To date, it is unknown whether healthcare professionals identify the limitations and risks of using unlicensed medicines. It is also not known whether they employ any strategies to minimise any potential risks, and how they balance these risks against a patient’s need. The quality of unlicensed medicine or any information on prescription remains unknown to patients too.
Things that prescribers should take care of before prescribing unlicensed medicines to patients
- They should be convinced that an alternative, licensed medicine will not be useful to the patient.
- They should be satisfied that an off-label medicine would be appropriate than a licensed alternative.
- They should take full responsibility for an unlicensed medicine, monitor their patients and ensure that it’s safe and effective for them.
- They should record the issues and reasons for prescribing an unlicensed medicine with the patient. This information is useful in the cases where common practice is not being followed.
During prescription of unlicensed medicines
- It is advisable to give patients sufficient information about the proposed treatment which also includes all kind of side effects and then, let them take the final call.
- The latest clinical practice supports the use of a medicine outside the terms of its license but it is recommended to give relevant information to patients or their caretakers.
- One should also explain the reasons for prescribing an off-label medicine or unlicensed medicine even when there is little evidence to support its use.
- It falls on healthcare professionals to monitor the safety of medicines in clinical use through submission of suspected adverse drug reactions to the MHRA and CHM. It is done via the Yellow Card Scheme.
Unlicensed Medicines in terms of economy
Let us talk about the economic aspects of unlicensed medicines. As per a research of top 500 items ordered in England and Wales, the average cost of an unlicensed medicine in 2014/2015 Quarter 1 was £104.47.
The most cheap items are Colecalciferol 20,000 unit capsules with an average price per item of £14.42 (43,717 items), and the most expensive ones are sodium benzoate tablets with an average cost of £807.19 per item (43 items). However, the fact remains that the average cost varies from treatment durations for each prescription.
Although Part VIIIB of the Drug Tariff, which came into effect from November 2011, seems to have caused an overall decrease in total spend on special unlicensed medicines in the primary care, but they continue to remain a cost burden to the National Health Service or NHS. It still remains to be seen if healthcare professionals take notice of this.
Increasingly, efforts are being made to take frequently used unlicensed formulations and create new licensed products. More and more new products are being introduced, unlicensed preparations for those products are being removed from the Drug Tariff list in the hope that patients could be supplied newly-available licensed preparations instead of unlicensed formulations. However, the case is not the same as it might seem. In May 2012, the unlicensed liquid preparations for Ramipril were removed from Part VIIIB of the Drug Tariff due to the introduction of the licensed Ramipril 2.5 mg/5 mL oral solution. However, in the financial period Quarter 1 2014/2015, a data report showed that there were still 355 cases of dispensed unlicensed items for Ramipril, costing the National Health Service £77 139.75 even though a licensed oral liquid formulation was available.
In addition, the top 10 unlicensed medicines in the prescribing data still include drugs for which there are licensed formulations available including Melatonin, Omeprazole, and Midazolam. It is still unclear why unlicensed medicines continue to be prescribed despite an increasing number of licensed alternatives.
Sunderland model of pharmacist practice support
Take a look at this example of pharmacist intervention in Sunderland, where clinical pharmacists provide support to general practices. This is delivered through a contract with a pharmacist support service paid by Sunderland Clinical Commissioning Group. However, the fact remains some practices prefer paying for additional pharmacists. There are examples in other regions where pharmacists are employed directly by the practice too, Cambridge for example. As a part of their work process in Sunderland, pharmacists will use NHS prescribing data to identify patients, their prescribed unlicensed medicines and review their therapy. Practiced pharmacists also liaise with hospital and community pharmacists to ensure that the patients are prescribed the most appropriate product to meet their clinical needs.
The potential role of pharmacists and their role in supporting appropriate use of medicines was highlighted as a part of the NHS England Clinical Pharmacists in General Practice Pilot. It included the example of ‘sorting out secondary care referrals for “specials” ‘as one of the potential roles for practice pharmacists.
Unlicensed Medicines – The way ahead
Despite several issues associated with the use of unlicensed medicines, very little information is available on the views of healthcare professionals on their use in practice. A lot of research is still required to explore the views of prescribers, pharmacists and patients on the use of unlicensed medicines across primary and secondary care. There is also a need to address some issues and to make healthcare providers aware of the rightful usages of such medicines.
Unlicensed medicines can majorly categorised into two parts:
- Products that are manufactured in the UK by a manufacturer’s “specials” license holder
- Products that are imported by an importer holding either a wholesale dealer’s licence enabled for handling unlicensed medicines (for products imported from within the European Economic Area, EEA), or a manufacturer’s specials licence enabled for importation from outside the EEA.
The prescription and use of unlicensed medicines come with a great responsibility. Despite being expensive, they are prescribed even when there are options of licensed alternatives available. It is advisable to both General Medical Council and medicines regulatory bodies to follow the guidelines on the use of unlicensed medicines. It also demands the liability of prescribers who choose to provide unlicensed medicines to patients.
Most importantly, one should understand the context of the use of unlicensed medicines. Be it a prescriber, patient or a pharmacist, everyone needs to know about rightful usages of unlicensed medicines. Without an in-depth understanding, it is difficult to propose systems and processes to ensure that patients, professionals, and the wider NHS use unlicensed medicines appropriately and safely.