Masterarbeit

ATMPs in Europe and Germany: From Regulatory Pathways to Reimbursement

Dr. Marina Pavlidou (2026)

Summary

Language: English

Advanced therapy medicinal products (ATMPs) are highly innovative therapies classified into gene therapies, somatic-cell therapies and tissue-engineered products. ATMPs are handled in the European Union (EU) under Regulation (EC) No 1394/2007 and are authorised via the centralised procedure. 

While they offer potential cures to diseases difficult to treat, their development is shaped by scientific, regulatory and economic uncertainty. Small patient populations, complex manufacturing, difficult comparators, limited long-term evidence at launch and very high upfront prices make ATMPs a stress test for conventional pharmaceutical frameworks. 

This master’s thesis examines the development pathways of approved ATMPs and the extent to which regulatory tools may have influenced them. It also critically examines the national use of the Hospital Exemption (HE) in selected EU countries to assess its impact on patient access and its role in the path towards centralised marketing authorisation (MA). In addition, it investigates health technology assessment (HTA) practices and their suitability for ATMPs to identify key areas of tension and evaluate how the new EU HTA regulation addresses them. Based on these findings, the thesis identifies areas for improvement and offers recommendations for streamlining and optimising ATMP development, reimbursement practices, and patient access.

In this work, development and reimbursement pathways of marketed ATMPs were reconstructed using information from official sources such as EPARs, national competent authority databases, the report “Study on the Hospital Exemption” by the European Commission (European Health and Digital Executive Agency) published in 2025 and G-BA benefit assessments supplemented with information from other sources such as company press releases, clinical databases and peer-reviewed literature.

A finding of this thesis is that existing regulatory tools improve development, reduce fees, support early scientific dialogue, accelerate regulatory interaction and reward products targeting unmet medical needs. The outcome of the performed analysis shows that ATMPs use regulatory tools (e.g. PRIME, orphan designation) disproportionally more often than non-ATMPs and that ATMPs that were granted conditional approval show overall shorter timelines to MA. However, this should not be interpreted as a direct correlation, as the sample size was small and other factors may also have influenced the results.

This thesis further argues that the HE embodies a compelling idea but an inconsistent reality. Conceptually, HE was intended to allow non-routine, custom-made ATMPs for individual patients in hospitals under medical responsibility, particularly where unmet need exists and commercial development is unattractive. In practice, implementation has diverged markedly between member states with substantial variation in quality requirements, evidentiary expectations, and the relationship between HE and centrally authorised products. Especially cartilage repair products in Germany seem to use the HE as parallel commercial track to the centralised MA. At the same time, HE offers opportunities for developers, patients and payers by using data and experience from the HE to facilitate the path to centralised MA, ensuring patients without alternative treatment options have access to therapy and providing cheaper versions of commercial ATMPs. HE approval holders for all ATMPs examined in this thesis show efforts in terms of parallel clinical development programmes to enable a future EU-wide authorisation of their ATMPs. Furthermore, the upcoming pharma legislation addresses some of the concerns of the current HE practices (e.g. centralised data reporting and collection).

A further finding of this thesis, using Germany as an example, is that reimbursement remains a decisive bottleneck. Under AMNOG, new medicines undergo early benefit assessment and later price negotiation, while orphan drugs such as most of the approved ATMPs benefit from a privileged starting position because additional benefit is legally presumed until the €30 million turnover threshold is exceeded. However, this does not eliminate the core challenges ATMPs face at the time of MA, including limited evidence, high upfront costs, and uncertainty about long-term durability, all of which may lead to lower reimbursement prices. These tensions led further to growing interest in outcome-based payment models as compromise between innovation and financial sustainability of the healthcare system. 

Against this background and since available tools and support for ATMP developers are rather fragmented, the thesis proposes a holistic tool for an ATMP-specific evidence and access pathway that addresses scientific, operational, and economic uncertainty right from the start. The tool integrates early regulatory and HTA advice, structured post-launch evidence generation, and provisional outcome-linked reimbursement within a single lifecycle framework. With such a tool promising therapies are not only authorised faster but also translated into predictable patient access.

Pages: 64

Annexes: 6, Pages: 19