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Dealing with requests for unlicensed medicines to be supplied to named patients is a legal and operational minefield. The ever expanding European marketplace means that named-patient demand is increasing, with more requests for new medicines being made directly by patients themselves, who are better informed because of the availability of information online, and pressure from patient groups.

However, the lack of clear pan-European regulation of named- patient programmes adds to already complex procedures, with all European countries offering access to named patients according to their own individual interpretations of the legislation. Therefore, a well planned and coordinated named-patient management (NPM) programme offers more than a system for supplying unlicensed medicines to patients who need them.

Within a drug's pre-launch strategy an NPM programme can help to build disease and product awareness, establish links with potential prescribers and reinforce relationships with KOLs. It can also contribute to a better understanding of the type of patients whom physicians see as most suitable for treatment, and provide valuable 'real life'prescribing data prior to launch. Requests to supply an unlicensed medicine used to be concentrated around treatments for life-threatening diseases, such as cancer, or for rare disorders requiring orphan drugs. But now both doctors and patients are requesting drugs to treat various conditions with unmet needs and demand for pre-licensed access to a broad range of promising new treatments is intensifying. Consequently, more companies are responding by implementing NPM programmes.

Even when a new medicine has received its European Medicines Agency (EMEA) marketing authorisation under the mutual recognition process, it can take many months before it gets to each of the 30 Member States of the European Economic Area. If there is no planned and coordinated NPM programme during this time, then patients are more likely to take their own steps to obtain the product they want; this, of course, exposes them to all the risks of inappropriate use that unregulated supply can bring.

Considering NPM assistance
The decision to embark on an NPM programme will be based on key decisions about the appropriateness of this strategy for a particular brand. It will also involve consideration of the ethical dilemma about which patients should get access to the product in the pre-launch phase. An NPM programme sets in motion an organised system for responding to requests from healthcare professionals and dealing with national legal requirements for importation of unlicensed medicines, ensuring prompt, reliable and cost-effective delivery of the required product. This is also a much quicker process than responding to requests on a case-by-case basis. More importantly, it can reduce the risk that patients will buy a medicine from an unlicensed source, use it inappropriately and experience unexpected adverse events, harming the product's reputation before it even reaches the market. A bespoke NPM programme can also provide invaluable physician endorsement, patient learning, real life data and the information needed to support forecasting models. Most pharma companies realise that doing nothing in the face of pre-launch demand is not an option.

The earlier the discussions about NPM programmes are initiated the better, so that more planning can go into the execution of the programme. Ideally, it should be considered at the start of phase III clinical trials, at the same time as the global marketing strategy for the brand is being planned. Regulatory affairs, medical, health outcomes and commercial departments all need to be involved from the start. In the case of a pan-European or worldwide programme, the scheme may be initiated centrally by the global marketing department or by the team in an individual country. Such a team may have had previous experience of NPM programmes or may be eager to follow up on specific named-patient requests. Once the marketing department of one affiliate proposes a programme to colleagues from other affiliates, it is remarkable how quickly everyone gets on board.

Yet, there are clear advantages for everyone to sign up at the initial planning stage, rather than trying it roll it out once it has started. At the beginning of the process, the programme can be designed to take account of the needs of all those taking part, not solely those who have initiated it.Each NPM programme must be tailored carefully to the individual needs of the specific product, which is why it is so important that there is medical, marketing, operational and strategic input from all those who collaborate on the project.

In-house or outsourced
Trying to plan a global or European launch can be complicated enough when a large number of local affiliates are involved. Establishing an NPM programme requires a detailed understanding of the legal requirements governing importation of unlicensed medicines, in each of the countries involved. Legislative implications are not the same across Europe. Most countries have their own individual regulations, some less clearly defined than others, within the broader European directive on the supply of unlicensed medicines. There may be an unwritten understanding to follow the regulations in place in another major EU country, or plans may be underway to develop new regulations. But finding a way through the bureaucratic red tape, with associated language barriers, can be very challenging.

For example, Portugal's regulations are relatively intensive requiring a great deal of documentation, while in Greece only the Institute of Pharmaceutical & Research Technology is permitted to import unlicensed medicines, therefore the centralised procedure is applicable when importing drugs on a named-patient basis. For smaller companies, the extra time needed to coordinate NPM may take key personnel away from other essential work at a vital time in a new product's life cycle. Even the largest pharmaceutical companies may balk at the investment of time and resources required to stay on top of the regulations.

Wyeth Pharmaceuticals found benefits in partnering with an NPM specialist, when running a global programme for tigecycline, an intravenous hospital antibiotic for life-threatening infections. Wyeth's R&D arm had run an NPM programme during the product's clinical development which, when the pivotal trials were completed, was taken over by its medical affairs department as the first launches of tigecycline were rolled out around the world. However, as the number of affiliates seeking to make use of the programme expanded, it placed unacceptably large demands on the medical and manufacturing departments at a time when the firm needed to focus on supplying the product for ongoing clinical trials.

'It was incredibly time consuming for medical affairs to process requests and ensure that the product was dispatched and received, and for the manufacturing department to make up the order with the correct packaging and to handle the paperwork' recalls Dr David McIntosh, medical director for infectious diseases, Global Medical Affairs, at Wyeth. This particular NPM programme was handed over to IDIS in November 2005, and is expected to continue for about two more years until tigecycline is registered in all its planned markets.

Dr McIntosh feels that the biggest advantage of having outsourced this project has been the time saved by the medical and marketing departments, which can now focus on their main priorities. He adds, however, that the main lesson in the process has been that such programmes need to be planned and initiated as early as possible, as it will save time in the longer term. By partnering with NPM specialists in such cases, pharma companies can benefit from their extensive resources, experience and knowledge of running NPM programmes, including the ability to handle and manage individual local affiliate issues. An NPM partner should be familiar with the complexities involved in managing the programmes and should already have systems for:

• processing named-patient requests
  
• applying and receiving import licences
  
• arranging for fast transport of the product - ideally from a central storage facility
  efficient delivery.

It should also be able to deal with all the legislative processes for importation of unlicensed medicines throughout Europe and advise on issues relating to pricing strategy and data capture. Well designed and executed NPM can provide useful pre-launch information on 'real world' prescribing. Screening systems need to be put in place to ensure that products are only prescribed to suitable patients. These patients are likely to reflect more closely those who will be taking the drug post-launch, compared with those in the carefully defined clinical trial conditions. Physicians who use products as part of an NPM programme are asked to contribute to adverse event reporting. This can provide useful insights into the safety of the product when it is used in clinical practice and help inform decisions about safety warnings and advice, which may be needed when the product is launched.

These benefits together with the emerging influence of the informed patient mean that an increasing number of pharma companies are seeing the advantages of an expertly coordinated multi-country NPM programme, providing an effective and responsible way to meet increasing demand from patients and doctors around Europe and beyond, particularly for promising new treatments that target an unmet medical need. If your drug could be a target for patient demand in the pre-approval stage, start planning as soon as possible.