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... Show moreAim: 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. Show less
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... Show moreBackground 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. (C) 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. Show less
Background aims: Recent technical and clinical advances with cell -based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need.... Show moreBackground aims: Recent technical and clinical advances with cell -based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and speci fic supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products. As a result, biomedical researchers and clinicians are increasingly faced with cost considerations in CBT development. The objective of this research was to develop a costing frame- work and methodology for academic and other small-scale facilities that manufacture cell -based therapies. Methods: We conducted an international multi -center costing study in four facilities in Europe using eight CBTs as case studies. This study includes costs from cell or tissue procurement to release of final product for clinical use. First, via interviews with research scientists, clinicians, biomedical scientists, pharmacists and techni- cians, we designed a high-level costing framework. Next, we developed a more detailed uniform methodology to allocate cost items. Costs were divided into steps (tissue procurement, manufacturing and fill - finish). The steps were each subdivided into cost categories (materials, equipment, personnel and facility), and each category was broken down into facility running ( fixed) costs and operational (variable) costs. The methodology was tested via the case studies and validated in developer interviews. Costs are expressed in 2018 euros ( ?). Results: The framework and methodology were applicable across facilities and proved sensitive to differences in product and facility characteristics. Case study cost estimates ranged between ?23 033 and ?190 799 Euros per batch, with batch yield varying between 1 and 88 doses. The cost estimations revealed hidden costs to developers and provided insights into cost drivers to help design manufacturing best practices. Show less
Wilde, S. de; Coppens, D.G.M.; Hoekman, J.; Bruin, M.L. de; Leufkens, H.G.M.; Guchelaar, H.J.; Meij, P. 2018
