Questions and answers about Compassionate Use Programme

It is best to ask your question via our contact form. You should indicate on the form that your question is about Compassionate Use. 

A CUP is intended for the treatment of a group of patients (a cohort) suffering from a chronic disease, a disease that is seriously detrimental to health or is considered life-threatening, and for which there is no registered alternative available. The manufacturer can submit a request for a CUP to the MEB.  

In the case of supply of an unauthorised product further to a Doctor’s Declaration, a Doctor’s Declaration is drawn up for an individual patient. A doctor can do this if, in their opinion, the patient cannot be treated with any medicinal product authorised in the Netherlands. The pharmacy, a wholesale supplier, a manufacturer or a dispensing general practitioner can use this Doctor’s Declaration to submit a request for permission to the Health and Youth Care Inspectorate (IGJ) to supply this medicinal product that is not authorised in the Netherlands. 

For further information on supply of an unauthorised product further to a Doctor’s Declaration, see the IGJ website.

An indication must be defined when applying for a CUP. Only patients with that indication are eligible to participate in the CUP. If non-responders of other treatment options meet the indication of the CUP, these patients are eligible to participate.

No, legislation does not provide the possibility for a CUP for a new indication of an authorised medicinal product, because the CUP legislation is based on an exception to supply an unauthorised medicinal product. For unauthorised indications of an authorised medicinal product, legislation regarding off-label use forms the legal basis. 

The manufacturer is obliged to collect all suspected adverse reactions. Suspected adverse reactions that may have a causal relationship with the medicinal product are sent by the manufacturer to EudraVigilance. The guidelines in Good Vigilance Practice Module VI are leading in this respect. If the programme has been running for more than a year, the manufacturer must submit a safety report with recent data. 

Furthermore, the manufacturer must contact the MEB if there are developments that give reason to reconsider the decision. For example, if the patients participating in the CUP can be treated with a newly approved medicinal product that was not available at the time of approval of the CUP, or if the manufacturer does not submit an application to the EMA or withdraws it, or if new serious adverse reactions occur. 

There are three criteria that a medicinal product must meet in order to qualify for a CUP:

1. The medicinal product must be intended for treatment of a group of patients suffering from a chronic disease, a disease that is detrimental to their health or a life-threatening disease.
2. This disease cannot be treated satisfactorily using an authorised medicinal product.
3. An application for a marketing authorisation for the medicinal product has been submitted, or clinical tests to support such an application are still ongoing. 

An application for a CUP can only be submitted by the manufacturer of the medicinal product.

If an authorisation application has already been submitted to the EMA, the authorisation dossier is already in the possession of the MEB, and the CUP application can refer to the authorisation dossier.   
If no authorisation application has been submitted to the EMA yet, include a substantiation with the CUP application on the basis of which the MEB can assess the CUP application. 

The application form contains further explanation about what information that substantiation must contain.  

The assessment consists of a number of steps:

1. After receiving the application, the MEB checks whether it contains all the necessary data to access the application. Within two weeks, the MEB will inform the applicant whether we can assess the application. If we need additional information, the applicant will also hear this within two weeks. 
2. The MEB will assess the CUP application and the applicant's substantiation on the basis of the set criteria. The assessment will subsequently indicate whether the balance between the efficacy and safety of the medicinal product is considered positive. 
3. The MEB will inform the applicant as soon as possible, but no later than six weeks after the start of the assessment. If the MEB cannot yet make a decision, we will ask the manufacturer to provide additional data. 

This concerns an overview of all relevant studies. These are studies that patients from the medicinal product’s target group can join. The overview should preferably contain a reference to the EU Clinical Trials Register.

No, the process of requesting a CUP is different for every country. A CUP request in the Netherlands will only be for the Netherlands. EU countries decide their own rules and procedures for a CUP. 

Yes. With a positive EC decision, the medicinal product is authorised in the EU, and therefore in the Netherlands. The MEB cannot approve a CUP for a medicinal product that has already been authorised. 

Before the EC decision, the CHMP will have drawn up an opinion. The MEB decision on the CUP can be taken in the period between the CHMP opinion and the EC decision. In the event that the EC has taken a decision and the MEB has not yet taken a decision on the CUP application, the application procedure will be terminated without the MEB taking a decision.

The manufacturer receives an approval for an indefinite period. This approval applies until the medicinal product has been granted a marketing authorisation, or earlier if, for example, it turns out that the balance between efficacy and harm is negative and the CUP must therefore end.

The CUP is subject to the condition that patients in the CUP continue to have access to the medicinal product until a positive reimbursement decision has been made for the medicine and it is commercially available.

Until 2023, approval was valid for a period of one year, after which an extension had to be requested. However, this is no longer the case. 

This cannot be determined in advance. If a new medicinal product is introduced, we must determine whether the CUP medicinal product still meets the CUP criteria. This mainly concerns the second criterion, whether there is no authorised alternative available. Possible outcomes are stopping the CUP or adjusting the indication for which the product can be used. 

Yes. Patients who did not previously participate in the CUP program may also be eligible for treatment. This can be done under the same conditions that apply to patients who received the medicinal product under the CUP and to whom it will continue to be supplied after the marketing authorisation has been granted (see also above ‘How long is a CUP valid?’). 

No, marketing authorisation holders do not have to report the marketing to the Medicine shortages and defects notification centre until after the reimbursement process has ended. The Medicines Act (Gmw) refers to ‘actual marketing’. The CUP concerns the provision to a specific patient group, which can continue after authorisation. This does not constitute ‘actual marketing’.

Immediately after the CUP medicinal product has been granted a marketing authorisation, the marketing authorisation holder must implement the aRMM in the Netherlands. This applies even if no decision on reimbursementhas been made yet. . The marketing authorisation holder must submit the aRMM to the MEB. The MEB will assess the aRMM against the requirements in the MEB 45 policy document. The marketing authorisation holder must therefore follow the instructions in MEB 45, and if the measures or the method of distribution of the aRMM deviates from the requirements in MEB45, the manufacturer must submit a justification to the MEB.

The continuity of the supply of the medicinal product is of paramount importance. The process of assessment and approval of the aRMM should therefore not hold up the supply. Patients must continue to have access to the medicinal product, even after the marketing authorisation has been granted.

Yes, it can. The manufacturer must inform the MEB when it intends to terminate the supply of the medicinal product after approval of a CUP. The MEB and the manufacturer should agree on the consequences for the patients of terminating the CUP. The manufacturer and the MEB will jointly determine which other parties will be asked to offer input.

As part of the CUP application, manufacturers must also submit a treatment protocol. The treatment protocol contains recommendations for healthcare professionals on how to safely and effectively administer and use the medicinal product. It contains relevant information on the clinical, pharmacological and pharmaceutical properties of the medicinal product. 

It also contains information on patient monitoring conditions, mechanism of action, effectiveness, important interactions, warnings, adverse reactions, dosage, special populations, inclusion and exclusion criteria and duration of treatment. The treating physician will receive this protocol within the programme. 

Yes, release in compliance with EU Good Manufacturing Practice (GMP) by a QP is required, regardless of the status of the marketing authorisation of the medicinal product. The company that releases the medicinal product must therefore have a European manufacturer's authorisation and an import authorisation (MIA).

No rules have been established for the packaging of the CUP medicinal product in the context of supply under the CUP. Since the medicinal product is not authorised, we recommend using the same language as for medicinal products that are provided in the context of clinical research.