Roadmap for making a medicine available
Are you a doctor or pharmacist and have identified a potentially suitable medicine for a patient with a rare disease, but the medicine is not yet available?
This roadmap helps you explore the different options to make the medicine accessible.
What are the options to make a medicine available to the patient?
Depending on the situation, there are four main routes to make a medicine available: registration (marketing authorization), off-label use, importation, and pharmacy compounding. Registration is generally preferred as it provides the highest guarantee of quality and safety. However, in some cases, registration may not be feasible (or quick enough). Below is a brief explanation of each route and the associated considerations.
Registration/marketing authorization of a medicine
In Europe, a medicine can only be marketed if it is registered, meaning it has a marketing authorization. To obtain this authorization, the medicine must meet strict requirements for quality, safety, and efficacy, usually demonstrated through large-scale clinical studies. This process can take several months to years, depending on the level of innovation and the complexity of the research.
Procedure: The application for marketing authorization is reviewed by authorities such as the FDA (USA), EMA (Europe), or CBG (Netherlands). These authorities assess whether the medicine meets the required standards and determine for which patient groups and conditions it may be used.
Considerations: Although registration is a time-consuming process, it provides the highest assurance of a medicine’s efficacy and safety. It also offers clarity on side effects, dosage, and proper application, which is crucial for safe use in practice. However, registration may not be possible in some cases due to existing orphan drug status or patents.
Off-label use of a medicine
Sometimes, a medicine approved for a specific condition or patient group is also found to be effective for another condition or group (e.g., children) for which it was not originally registered. This is known as off-label use and can provide a solution when no registered medicine is available for a specific rare disease.
Procedure: Off-label use is allowed under certain conditions and requires the doctor or pharmacist to scientifically justify why the medicine is suitable for the specific disease. Patients must also be informed about the potential benefits and risks, as off-label use falls outside the original registration.
Considerations: Off-label use can be a solution when no registered treatment is available but carries certain risks. There is often no specific evidence of efficacy and safety for the intended condition, making outcomes less predictable. Availability may also be uncertain, as the medicine could be withdrawn from the market. Patients might receive packaging and instructions intended for another condition, leading to confusion. Additionally, monitoring of side effects is often lacking, requiring extra caution.
Importing a medicine (the 3.17 route)
If a medicine does not have a marketing authorization in the Netherlands or Europe, importation may be a solution. This route is often applicable when the medicine is available in other countries but not yet in the Netherlands or Europe. The 3.17 route can be considered for medicines that are already safely used elsewhere but lack approval in the Netherlands.
Procedure: To import a medicine via the 3.17 route, permission from the Dutch Health and Youth Care Inspectorate (IGJ) is required. The doctor must submit a declaration to the IGJ explaining why the medicine needs to be imported and the risks if it is unavailable.
Considerations: There is no guarantee of long-term availability, as importation depends on supply in other countries. Moreover, the quality, efficacy, and safety of the medicine have not been assessed by a European authority, meaning some safeguards may be missing. This route also involves additional administrative burdens for pharmacists to make the medicine available.
Pharmacy compounding/magistral preparation
Pharmacists can sometimes prepare a medicine themselves if it is unavailable, provided high-quality ingredients are accessible and the medicine is suitable for compounding. This magistral preparation often provides a solution for patients requiring special dosages or formulations not commercially available.
Procedure: Pharmacists with their own compounding facilities can prepare medicines themselves, provided they meet strict quality requirements. Pharmacists without their own facilities can collaborate with colleagues who do, allowing them to provide compounded medicines to their patients under strict conditions.
Considerations: While this method allows for customization, there are drawbacks: quality and efficacy are not tested in the same way as with registered medicines, and necessary ingredients may not always be available. Pharmacy compounding is typically a temporary or individual solution and often does not provide a long-term structural fix.
How do I determine the best option?
The most suitable route depends on multiple factors, including the specific condition, the availability of the medicine, and the required speed. A marketing authorization or registration provides the most long-term assurance and safety for patients. Consider alternative routes only if registration is not feasible in the short term.