OBJECTIVES : The increasing use of gene therapeutics and other high-priced drugs for rare diseases poses enormous challenges to the healthcare system. Although patients with severe diseases may profit substantially from the innovations, drugs basically may only be marketed in Germany if they have been approved within their indications by Federal authority or by the European Commission (§ 21 AMG). Use may be granted in the context of “off-label-use”, “no-label-use”, and “compassionate use”.

METHODS : Guidelines from EMA, G-BA, IQWiG, and respective legislations were reviewed and analyzed. Decision criteria and reasoning as well as funding were the main aspects for this evaluation. Based on representative examples, we describe the challenges for possible reimbursement of a treatment with an unauthorized drug.

RESULTS : The reimbursement requirements for “no-label” use are not fundamentally different from the requirements for “off-label use” (e.g. Alemtuzumab). So-called „Named patient use” drugs may lawfully be imported into Germany via § 74 (3) AMG if there is a therapeutic need and the drug has been legally marketed in the country of origin (e.g. Onasemnogene Abeparvovec-xioi). However, reimbursement requirements are more restrictive. The “compassionate use” program enables treating life-threatened patients without alternative therapies with non-approved drugs. However, the costs incurred have to be borne often by the pharmaceutical manufacturer.

CONCLUSIONS : Due to the current development, the following challenges arise for the German health system: 1) the development of new drugs for rare diseases is more and more often accompanied by a high price. 2) Due to the lack of therapeutic alternatives, the call of an immediate availability of these treatments, even before the official approval, is high and 3) the reimbursement of these new treatments will have to be determined individually in a time-consuming process between payers and manufacturers. Therefore, the establishment of a process that is transparent and comprehensible for all stakeholders will be essential.