Unlicensed use of medicines

Table 3.4 General lequiiemcaits for off label and unlicensed use of medicines. Authorisations may differ according to national and local ordinances...

As well as ensuring that the prescriber is aware of the unlicensed use of the medication it is important to bring this to the attention of the patient. This should be done without undermining the patient s confidence in either the prescriber or the prescribed medicine. This is also necessary because the patient information leaflet which you are supplying with the medication will not include anything to suggest that the product can be used in sickle cell anaemia. 

This provision allows Member States if they wish (there is no obligation to do so) to make national arrangements for the supply of unlicensed medicines for particular use, but only in the very limited circumstances specified by the Directive. As part of the 2001 review process, the European Commission recently issued proposals to regulate the compassionate use of medicinal products falling within the scope of Regulation 2309/93/EC (the centralised procedure). However, these proposals are unlikely to come into force for several years. 

It is then necessary to review the meaning of special needs. It is difficult to see how such needs can exist where there is a licensed version of the product on the market for the physician to use. However tempting it may be for medical institutions to save costs by requesting an unlicensed version of a licensed product, economic needs will never be special needs in this context. This accords with the rationale underlying the Directive, which requires only authorised medicinal products to be placed on the market unless exceptional circumstances apply. 

The widest use of unlicensed medicinal products is in the course of clinical trials. It is important to distinguish between clinical trial use and particular patient use, as very different rules govern these different types of use. 

Where a company suspects that the product is to be used in a way that is not safe for patients, its duty to those patients may involve warning the doctor that it considers the proposed use to be hazardous and, if necessary, refusing or terminating supply. While there is no general obligation to provide product information with unlicensed medicines (and, as noted above, the use of promotional material is prohibited), from a product liability standpoint, the provision of basic safety information about the product is a sensible precaution. 

In Guidance Note 14, the Medicines and Healthcare Products Regulatory Agency states that hospital trusts, health authorities and independent hospitals should have clear policies on the use of unlicensed medicines, explaining liability considerations and requiring all those involved in the supply chain to ensure that the unlicensed status of a product is commimicated and fully understood. 

Chinese immigrants were often blamed for bringing opium to America, but opium had been present in America for some time, both in its raw form and in countless medical concoctions created by patent medicine makers, the unlicensed pharmacists of the day. Nevertheless, the wave of Chinese immigrants, who had used opium in China or picked up the habit in America, enhanced the demand for opium and thus expanded the market. 

Royal Pharmaceutical Society of Great Britain (RPSGB) (2007) Fitness to Practice and Legal Affairs Directorate Fact Sheet Five. The use of unlicensed medicines in pharmacy. http //www.rpsgb.org/pdfs/factsheet5. pdf [Accessed 4 July 2008],... 

The Ph. Eur. defines preparation (of an unlicensed pharmaceutical preparation) as the manufacture of unlicensed pharmaceutical preparations by or at the request of pharmacies or other healthcare establishments (the term preparation is used instead of manufacture in order clearly to distinguish it from the industrial manufacture of licensed pharmaceutical preparations). As many situations apply to production of medicines in (hospital) pharmacies, the term preparation is used most in the book. Sometimes it is quite obvious that it concerns manufacturing. Compounding , as a term for small-scale preparation often used in the US, is not used in this book. 

Medicines are available for patients as authorised medicines or as pharmacy preparations (unlicensed medicines). Market logic ensures that only medicines with sufficient return on investment will be marketed. However, health care logic requires pharmacists to provide their patients with necessary medicines. There are regulations that cover medicines for clinical research, marketing authorisation and import, as well as traffic between European countries (parallel imports). If medicines are not available as authorised medicines, various options such as compassionate use or parallel trial programme can be considered. The authorisation of medicines for orphan diseases is promoted by the orphan dmg regulations. The system of reimbursement will be discussed briefly due to its special situation at the interface of both public health and social insurances. 

Compassionate use is a treatment option that allows the use of an unlicensed medicine. Compassionate use programmes are for patients in the European Union (EU) who have a disease with no satisfactory authorised therapies or cannot enter a clinical trial. They are intended to facilitate the availability to patients of new treatment options under development. To qualify for a compassionate use programme, the manufacturer calls on the national authorities for permission. The manufacturer must submit a request for the granting of a marketing authorisation or he must perform research in the context of a research programme with a cohort. Compassionate use procedures are also applicable for unlicensed medicines withdrawn from the market or for off-label use of licensed medicines. 

By analogy with monographs on specific products for parenteral use, such data are also wanted and in some countries already compiled for oral solid medicines. The pharmacist can consult the manufacturer about cmshing tablets. However, if this information about cmshing is not in the SPC, cmshing means using the medicine in an unlicensed way. Therefore it may be useful to record the reasoning of decisions made (for instance by one of the forms in Sect. 2.2). 

An example of a scenario v/hen a medicine use is unlicensed is v/hen an adult oral dosage form is changed to a liquid formulation for administration to a paediatric patient. 

The term exploratory development (ED) can be defined as the first part of clinical drug development in which tolerabihty, pharmacokinetics and pharmacod)mamic activity are defined in man and in which an early indication of therapeutic efficacy is often obtained. A new molecular entity (NME) can be defined as an unlicensed new chemical or biological entity with activity in biological systems whose therapeutic potential is under investigation. The overall aim of ED should be to select appropriate NMEs for full development (ED), that is, commitment to licence application and to reject those that will not make useful medicines, as early as possible. 

This provision allows Member States if they wish (there is no obligation to do so) to make national arrangements for the supply of unlicensed medicines for particular use, but only in the very limited circumstances specified by the Directive. 

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