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Challenges of using unlicensed medicines throughout Europe


André Rieutord
PharmD PhD HDR

Hospital Pharmacist

Pharmacy Service
Robert Debré Children’s Hospital

E: [email protected]

Drug sourcing and supply has long been the main task of the pharmacist. Now, the world is changing fast. Every day, ­information emerges about medicines and patients’ needs become more and more specific ­according to the ­latest developments in new therapies from ­anywhere in the world. The challenge for ­pharmacists now is to source their supplies and dispense a specific and safe drug for a particular patient at very short notice. This medicine could be under clinical trials or ­unlicensed in the country where it is needed.

At the European Association of Hospital ­Pharmacists’ congress in Bordeaux, France, in March 2007, the problems of sourcing and ­supplying ­unlicensed medicines were addressed in a symposium.(1) The topic was in line with the ­conference’s main theme: “New therapies in the 21st century: challenges for hospital pharmacy”. During the ­symposium, three speakers discussed risk minimisation and guarantees of using safe ­medicine, with practical examples given in the areas of oncology and paediatrics.

Unlicensed medicinal products (UMPs) fall into four types: medicines currently under clinical trial, medicines licensed outside the country in question, discontinued products and specially formulated (“special”) products. Unlicensed medicines are important to pharmacy for several reasons:

  • They represent a significant proportion of hospital and pharmacist workload.
  • Managing demand is often difficult.
  • Available clinical information is limited and the quality of the product coming from abroad is unknown.

France, Germany and the UK have different ­regulations for UMPs and a risk assessment can and should be carried out to minimise the risks.

UMPs must be assessed by the pharmacist according to a clear quality assurance programme. This should at least include a quality control check (quality of label and packaging, review of certificate of ­analysis, comparison with specification) and a patient information leaflet in the appropriate ­language. In the meantime, the drug and therapeutic committee (DTC) should issue clear policies aimed at managing risk for UMPs, covering such issues as reviewing clinical usage for new UMPs and monitoring and auditing their use. In practice, the clinical pharmacist will ensure that the prescriber and patient are aware of UMP status, obtain DTC approval, prepare product specification and report any adverse reactions.

UMPs in oncology: the example of Germany
Oncology drugs which need to be imported into Germany are those which are no longer approved or which never have been, or are not yet licensed in the country (eg, respectively, teniposide, ­daunorubicin; streptozocin, fotemustin; and ­azacitidine). ­Occasionally it can also be other drugs that are unavailable due to a shortage in Germany. Dr Irene Krämer (­Director, ­Pharmacy Department, Johannes Gutenberg ­University Hospital, Mainz, Germany) said that of the drugs imported into ­Germany, ­oncology drugs were the most expensive and most frequently imported. Why? On the one hand, these drugs form part of internationally established ­protocols. On the other hand, physicians sometimes look for new treatment options for extensively treated terminally ill patients, while at the same time patients may ask for further treatment with novel drugs when ­terminally ill or ­following information retrieval from the Internet.

The hospital pharmacist will attempt to source such drugs from international ­manufacturing ­companies or specialist suppliers, although ­succeeding may often be a struggle due to such ­factors as customs formalities. Dr Krämer ­demonstrated the ­advantages of importing via specialist ­suppliers: they have the knowledge of the market and of other suppliers, they supply product information and ­support in translation, they have short delivery times and they deal with customs clearance and regulations on ­narcotic drugs.

UMPs in paediatrics: the case of France and Europe
It has been widely reported that up to 65% of drugs used in children are used off-license, and even if they are licensed for use in children there is often ­inadequate dosing information or no ­paediatric ­dosage form. This leads hospital pharmacists, as well as community pharmacists, to make up ­magistrals which are not usually fully assessed and tested. Therefore, the patient could receive a ­product with a different bioavailability and end up under- or overdosing.

A pharmacist who manufactures or prepares an unlicensed medicine in response to a prescription is professionally accountable for any harm caused by a defect in the medicine which is ­attributable to his or her own actions or omissions and ­subject to ­negligence liability. It is acknowledged that ­compounding extemporaneous dispensing is more hazardous than importing a licensed ­product from outside the country. A practical example which addresses all the relevant issues in paediatrics ­follows. At Robert Debré Children’s Hospital in Paris, diazoxide capsules are made available for a total cost of roughly €150 (including compounding and testing). This magistral is then delivered to parents or nurses who have to manage the critical administration of capsules to children without the benefit of an information leaflet. In contrast, importing the licensed 50 mg/ml solution from Canada costs about €200. The product is safe and effective, comes with a patient leaflet and can be administered easily using an appropriate syringe.

In Europe, legal regulations governing procurement of difficult-to-obtain medicines vary widely from country to country. When innovative therapies are needed, it is frequently necessary to turn to the global market because pharmaceutical products are not always ready for marketing in every country at the same time. Specialist service providers can help pharmacists save time and minimise risks.

Compounding extemporaneous dispensing must be avoided when there is licensed product available outside the country. With respect to clear policies on importation this is demonstrably safer and cost-effective.

A specialist provider can offer a rapid service to pharmacists in difficult cases. Such service can be guaranteed because the provider uses an efficient international courier service and works closely with the responsible authorities.

This could eventually allow pharmacy ­managers to reorganise their workloads and spend more time on valuable activities such as clinical pharmacy. All over Europe, pharmacists are willing to develop patient-centred activities but struggle to find some way to develop these. Outsourcing such a time-consuming service to specialist providers certainly creates one way to undertake new, interesting and relevant pharmacy activity.

1. Karr A, Krämer I, Rieutord A. Challenges of using of unlicensed medicines throughout Europe. Satellite symposium, European Association of Hospital Pharmacists Congress, Bordeaux, France, 21–23 March 2007.

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