In dispensing most medicines to patients, pharmacists can feel confident that the product has been through the rigorous inspection and licensing processes controlled by the Medicines and Healthcare products Regulatory Agency (MHRA) to ensure its safety, quality and efficacy. The product will be 'licensed' and will carry an appropriate product licence number.
Occasionally, however, a pharmacist will receive a prescription for an 'unlicensed product', which has been prescribed by the doctor (often after initiation by a hospital consultant) because there is no suitable licensed alternative for the particular patient. There may be a number of reasons why the product is unlicensed:
There may be no commercial justification for a manufacturer to undertake the necessary processes for a licence in the UK i.e. there are relatively few patients that will require it.
- The product may still be in its clinical trial phase or be awaiting approval by the MHRA.
- The licence for the product may have been withdrawn, for safety concerns, but it remains available in a limited way on an unlicensed, named patient basis.
While the prescribing doctor takes responsibility for the prescribing decision, the challenge to the pharmacist will be to dispense it, confident in the knowledge that it has been sourced and provided in a way that will, as far as is professionally possible, protect patient safety.
The MHRA undertakes a number of processes to help pharmacists do this and has issued a guidance note (GN14) to manufacturers, distributors and health professionals outlining the necessary specific conditions for supply. The key elements of GN14:
Pharmacists should confirm with the supplier that the product is for an individual patient. Although the process is often defined as 'named patient supply' there may be no specific need for the pharmacist to provide the name of the patient, although this is often done, and it is good practice for records to be kept at least in the pharmacy.
- All within the supply chain should be aware that the product is 'unlicensed'. The pharmacist should inform a prescriber if they are in any doubt that they are aware of the status of the product.
- Pharmacists need to be confident that the manufacturer and supplier hold the necessary licences required for the provision of an unlicensed medicine.
Such suppliers are regularly inspected and audited by the MHRA to ensure specific standards are maintained:
If the product is imported, the supplier needs to have notified the MHRA well in advance (28 days) and allow the MHRA to carry out any necessary safety checks before approval.
- If the product is manufactured as a special in the UK then a qualified person will ensure that it has complied with Good Manufacturing Practice (GMP) standards and the GMP inspector will also check labelling, stability data and expiry information.
- Licensed distributors and manufacturers will take responsibility for maintaining adequate batch records and traceability so that a 'batch recall' could be facilitated if necessary on the unlicensed product. Distributors should also have the facility to receive/record any adverse events and communicate effectively with the manufacturer and MHRA to ensure any appropriate actions are taken.
- Due to stock shortage or manufacturing problems, there may be a need for imported unlicensed medicines to maintain essential supplies. Manufacturers now have a legal obligation to advise the MHRA of any interruptions of supply to the market
All of these conditions are designed to ensure pharmacists are confident in supplying unlicensed medicines but vigilance is required at all times as there are occasions when a product can be supplied, perhaps quite inadvertently, which infringes the regulations. Two recent examples - co-proxamol and melatonin - illustrate this point.
Pharmacists will be aware that the licence for co-proxamol was withdrawn by the MHRA at the end of December 2007 due to concerns over the level of deaths - accidental and suicidal - caused by overdose, particularly when associated with alcohol intake.
The MHRA decided to allow the continued use of co-proxamol on an unlicensed, named patient basis, following calls from health professionals and interested patient groups who recognised the importance of the medicine for particular patients.
While the number of patients needing co-proxamol has significantly declined over the last 10 months (from over 100,000 patients taking co-proxamol in December 2007), it is still one of the most widely prescribed unlicensed products, with most pharmacies dispensing to at least one or two patients per month.
The situation with co-proxamol has been further complicated by two significant factors. The Department of Health (DH) has listed co-proxamol as a category C product in the Drug Tariff. This is highly unusual for an unlicensed product, but probably reflects a need for the DH to control the overall cost.
Secondly, there has been a significant continued use of residual 'licensed' packs in the supply chain despite a request on two occasions by the MHRA for all such packs to be returned to the original marketing authorisation (MA) holders.
On 20 August the MHRA wrote to pharmacy superintendents and original MA holders asking, again, for pharmacists to dispense a legitimate 'unlicensed pack' of co-proxamol in order to establish some clarity and continuity for doctors and patients moving forward. This followed the MHRA's position back in December 2007 that:
"...no further stock should be released into the normal distribution chain by MA holders or their agents after 31 December 2007. However, following withdrawal of the MAs it will remain legal to continue to supply co-proxamol released into the normal distribution chain prior to 31 December 2007 up until the product expiry date on the label has passed.
"To ensure any surplus stock is removed from the market once the MAs have been withdrawn, the MHRA has asked MA holders to undertake a voluntary withdrawal of stock and put in place arrangements to receive returned stock from both wholesale distributors and pharmacies (both community and hospital)."
The situation has led to some confusion with pharmacists not knowing whether an unlicensed or previously licensed pack would be supplied by their wholesaler, or if they could even source the product at all.
Such complexities can sometimes lead to either inadvertent or deliberate but unscrupulous activities, and indeed in September 2008 a pack of unlicensed co-proxamol was released into the UK supply chain which was, reportedly, manufactured for export only.
This situation is currently under investigation by the MHRA. In all respects, other than a lack of product licence number, it resembled the pack that the patient had previously been provided.
In this case, the risk to patient safety was considered low, as the MHRA established early on that the constituents of the illegal pack were not harmful. However, the fact that so many packs were dispensed to patients without pharmacists realising demonstrates how vigilant pharmacists need to be when sourcing an unlicensed medicine: such a pack could easily have been counterfeit.
The current situation with melatonin provides another example where the complexity of unlicensed medicine provision puts a challenge on the pharmacist. Most pharmacists will be familiar with dispensing melatonin as it has been a widely used unlicensed medicine for some years.
The recent launch of a licensed form (just one strength and modified release only) has created significant confusion. Can the unlicensed medicine still be prescribed? Can it be dispensed and under what conditions? Is imported unlicensed melatonin still allowed and under what conditions? Is a doctor's letter necessary for all versions? Do the same conditions apply to UK GMP approved melatonin?
A letter from the MHRA has gone some way to assure pharmacists: yes, unlicensed forms are still needed by many patients (different dose, immediate release); imported melatonin is more restricted, and letters of justification for import are needed as there is more confidence in UK GMP approved versions etc.
Both these recent examples highlight the need for pharmacists to be vigilant and think about the sources they use for the supply of unlicensed medicines. Here are our recommendations:
Ensure your supplier has the right licences to distribute and ask whether they have checked that the manufacturer has the right licence for supply to the UK.
- Choose a supplier for your unlicensed medicine who has a responsive and informative customer service team who can answer, with confidence and knowledge, some of the questions that you would like answered.
- Check that your supplier can provide you with an ongoing supply of the same unlicensed product.
Following these recommendations will provide pharmacists with peace of mind when dispensing an unlicensed medicine.
Scott Smith is Commercial Director of Clinigen Healthcare and Rob Darracott is CEO of the Company Chemists' Association (CCA).