1. Requirements for compassionate use

CUP is an arrangement manufacturers can use to make a medicinal product without granted marketing authorization (MA) available for a group of patients. Before a CUP can be initiated, NoMA has to assess and approve the application. The applicant is the manufacturer of the medicinal product in question.

For a CUP application to be approved, the following requirements must be met:

  • CUP is only for patients with chronic, life-threatening, long-lasting or serious disabling diseases
  • CUP is only for patients that cannot be included in ongoing clinical trials and that do not benefit from the use of medicinal products with MA
  • The benefit-risk ratio for the patient population of interest must be positive, supported by sufficient evidence on the effect and safety of the medicinal product
  • The applicant has submitted an application for MA and/or has ongoing clinical trials with the medicinal product in question

 

2. Documentation to be submitted

​Cover letter

The cover letter must contain information regarding previous and/or ongoing clinical trials with the medicinal product in question. If there has been, or is ongoing, clinical trials in Norway please refer to the respective EudraCT-numbers, as well as NoMA reference numbers.

Information on application for marketing authorization

If an application for MA has been submitted, NoMA must be notified. If so, the application must include the reference number for the MA application and the date of submission. This information can be provided in the cover letter.

Justification

The need of a CUP must be justified, reasoning why the patients cannot be satisfactorily treated with approved medicinal products. In addition, it must be justified why the patients cannot be included in an ongoing clinical trial.

Safety monitoring

The application must contain a description on how adverse reactions will be registered and reported.

Protocol (project plan)

There are no formal requirements on the content of a CUP protocol. For guidance, chapter 6 in ICH GCP and chapter 4 (page 10 and 11) in the Guidance on the Norwegian regulation on clinical trials may be used.

Informing the patients

There are no formal requirements on the content of the patient information. For guidance, the template published by Regional Ethics Committee on clinical trials may be used

Labeling

A label suggestion must be submitted with the application.

Benefit/risk assessment

Unless described in the protocol, a benefit/risk assessment has to be submitted with the application. The assessment must address the risks of using the medicinal product with respect to the potential benefits for the intended patient population. The benefit/risk assessment must contain a summary of the results from clinical trials where patients with the indication in question have been included.

Documentation of the medicinal products

  • If the application involves the use of a new active substance, or a new formulation of an already authorized substance, pharmaceutical documentation must be submitted. The investigator’s brochure must be submitted.
  • A list of all previous and/or ongoing clinical trials must be submitted. A reference to the corresponding EudraCT-number(s) should be made, if available, as well as the NoMA reference numbers if any trials has been performed in Norway.

List of included patients

The responsible physician must have a list of all patients in the program. The list must be continuously updated while patients are included in the program. The applicant must once a year submit an update to NoMA regarding the number of patients included in the program.

3. Financing the medicinal product


The medicinal product must be free of charge for the patients included in the CUP. It is up to the manufacturer, the responsible institution and potentially the pharmacy to agree on the cost of the medicinal product.

4. Authorizations import and manufacturing

​The regulation of import of medicinal products to be used within a CUP is the same as for import of other medicinal products. Medicinal products can be imported by businesses or hospital pharmacies with import authorizations. Within EEA, only import authorization is required, whereas outside EEA (third countries) it is necessary with manufacturing authorization in addition.

Authorization for manufacturing is granted by NoMA. Amongst others, a manufacturing authorization implies that there must be a qualified person (QP) to import the medicinal product. The QP has to make sure that all formal requirements to both the medicinal product and the transportation (from countries outside EEA) are met.

5. Approval

  • ​NoMA makes decisions according to § 2-8 in the Norwegian regulation on medicinal products.
  • The application must meet all the requirements for the compassionate use program. All documentation described must be submitted for the evaluation of the application to begin (see step 2).
  • NoMA can approve CUP for a limited period or grant a conditional approval. If an extension is necessary, a substantial amendment must be submitted for approval.
  • There is no fee on applications for CUP.

Time to decision

NoMA aims to respond to all applications for compassionate use within 35 days. However, for CUP applications, there are no legal requirements for the time to decision.

6. Follow-up

​Reporting of adverse reactions is as for products with MA, described in Regulation (EC) 726/2004, article 24(1) and article 25.

Substantial changes to the protocol must be submitted for approval as a substantial amendment. Substantial amendments include changes that can have a substantial influence on the safety of the patients, their physical/psychical integrity or the quality and safety of the medicinal product itself. The substantial amendments are assessed according to the same guidelines as for clinical trials. If NoMA has not commented on the substantial amendment within 35 days, the amendment is considered approved.

The applicant has to submit an annual report to NoMA. The report must include the number of patients included in the program, an updated risk/benefit assessment of the product and a line listing of all serious adverse events.

When a medicinal product used in a CUP is granted MA and the price is set, the proprietor of the MA must submit updated information to NoMA regarding the CUP within 30 days.

Patients already included in the CUP can continue in the program after the medicinal product has been granted MA and the price has been set, if the responsible physician deems it necessary. However, new patients cannot be included in the program.

7. Termination

​NoMA can close a CUP if it is deemed necessary, e.g. due to safety issues.

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Publisert: 29.01.2018

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