OBJECTIVES : Advanced therapy medicinal products (ATMPs) are based on viable cells or tissues and show a complex mode of action. European approval relies on specific regulations and involves the European Medicines Agency’s Committee for Advanced Therapies. Here, the evaluation of German HTA authorities (Federal Joint Committee, G-BA) regarding the quality of evidence and possible options to improve the data basis for ATMPs (e.g. via evaluation of registry data) will be discussed.

METHODS : A list of all centrally or regionally approved ATMPs was retrieved from the Paul-Ehrlich-Institute and the EMA. Information regarding the assessment of the added medical benefit according to AMNOG, the evidence basis and the outcome of the assessment was collected from the website of G-BA.

RESULTS : To date 21 ATMPs have been approved in Germany (eight gene therapeutics, two somatic cell therapeutics, one tumor vaccine, ten tissue engineered products). Five gene therapeutics and both somatic cell therapeutics were obliged to AMNOG assessments so far. None of the assessments revealed a quantifiable added benefit. ATMPs approved for Orphan Diseases reached a nonquantifiable added benefit due to specific regulations for Orphan Drugs in Germany.

Three benefit assessments presented data of randomized controlled trials whereas four assessments are based on single arm studies. In three cases data from post authorization studies (e.g. registry data) were demanded for follow up assessment by G-BA.

CONCLUSIONS : Approval studies in ATMPs often show limited evidence due to the small number of patients. RCTs have been conducted for some ATMPs but feasibility strongly depends on the size of patient population. For single arm studies, G-BA requested to submit additional evidence (RCT or registry data) to a later date. German authorities are currently preparing a draft law to make additional data acquisition (e.g. registries) legally binding if the approval data are insufficient for the benefit assessment according to AMNOG.