No abstract

Aim: To study regulatory approaches for the implementation and utilization of the Hospital Exemption (HE) in nine EU countries. Materials & methods: Using public regulatory documentation and interviews with authorities we characterized the national implementation process of the HE, including national implementation characteristics and two outcomes: national licensing provisions and the amount of license holders. Results: National licensing provisions vary substantially among selected countries as a result of different regulatory considerations that relate to unmet medical needs, benefit/risk balance, and innovation. The amount of license holders per country is moderate (0–11). Conclusion: The HE facilitates HE utilization in clinical practice in some countries, yet safeguarding of public health and incentivizing commercial development is challenging.

Background aims: As part of the advanced therapy medicinal product (ATMP) regulation, the hospital exemption (HE) was enacted to accommodate manufacturing of custom-made ATMPs for treatment purposes in the European Union (EU). However, how the HE pathway has been used in practice is largely unknown. Methods: Using a survey and interviews, we provide the product characteristics, scale and motivation for ATMP manufacturing under HE and other, non-ATMP-specific exemption pathways in seven European countries. Results: Results show that ATMPs were manufactured under HE by public facilities located in Finland, Germany, Italy and the Netherlands, which enabled availability of a modest number of ATMPs (n = 12) between 2009 and 2017. These ATMPs were shown to have close proximity to clinical practice, and manufacturing was primarily motivated by clinical needs and clinical experience. Public facilities used HE when patients could not obtain treatment in ongoing or future trials. Regulatory aspects motivated (Finland, Italy, the Netherlands) or limited (Belgium, Germany) HE utilization, whereas financial resources generally limited HE utilization by public facilities. Public facilities manufactured other ATMPs (n = 11) under named patient use (NPU) between 2015 and 2017 and used NPU in a similar fashion as HE. The scale of manufacturing under HE over 9 years was shown to be rather limited in comparison to manufacturing under NPU over 3 years. In Germany, ATMPs were mainly manufactured by facilities of private companies under HE. Conclusions: The HE enables availability of ATMPs with close proximity to clinical practice. Yet in some countries, HE provisions limit utilization, whereas commercial developments could be undermined by private HE licenses in Germany. Transparency through a public EU-wide registry and guidance for distinguishing between ATMPs that are or are not commercially viable as well as public-private engagements are needed to optimize the use of the HE pathway and regulatory pathways for commercial development in a complementary fashion.

Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation.

A comparative analysis of assessment procedures for authorization of all European Union (EU) applications for advanced therapy medicinal products (ATMPs) shows that negative opinions were associated with a lack of clinical efficacy and identified severe safety risks. Unmet medical need was often considered in positive opinions and outweighed scientific uncertainties. Numerous quality issues illustrate the difficulties in this domain for ATMP development. Altogether, it suggests that setting appropriate standards for ATMP authorization in Europe, similar to elsewhere, is a learning experience. The experimental characteristics of authorized ATMPs urge regulators, industry, and clinical practice to pay accurate attention to post-marketing risk management to limit patient risk. Methodologies for ATMP development and regulatory evaluations need to be continuously evaluated for the field to flourish.