Regulating Advanced Therapy Medicinal Products through the Hospital Exemption: An Analysis of Regulatory Approaches in Nine EU Countries

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.

Patient access to and ethical considerations of the application of the European Union hospital exemption rule for advanced therapy medicinal products

“…The differences among EU Member States in the transposition and implementation of HE at a national level have been recently analyzed in detail [6,11,12], including variability in the implementation characteristics, requirement set and outcomes across EU countries. Therefore, this article neither reviews the HE approaches nor links specific approaches to a specific country.…”

“…Moreover, in some countries, the products were processed in publicly funded tissue establishments, whereas in others they were processed by companies holding tissue processing licenses. Therefore, the HE clause allowed some flexibility and enabled different Member States to fit their individual circumstances into the ATMP regulation [10,11].…”

“…Although each Member State may only permit HE when the conditions in Article 28 of the ATMP regulation are met, countries may operationalize these conditions differently. Therefore, the extent to which HE is applied varies among EU countries [6,11,12]. Consequently, the requirements for granting HE are also different depending on the situations where HE is permitted to be used.…”

“…In this regard, although some countries require quality to be fully compliant with Good Manufacturing Practice as well as both non-clinical and clinical evidence, others do not. As a general rule, riskÀbenefit approach and safety reporting are strictly required regardless of how HE has been implemented [6,11]. This lack of harmonization of HE implementation has been the subject of intense debate as a result of misunderstanding in non-EU countries and the uncertainties that might be detrimental to EU competitiveness.…”

The UK’s emerging regulatory framework for point-of-care manufacture: insights from a workshop on advanced therapies

“…Since freshly delivered ATMPs have these particular characteristics, it has been challenging to formulate and implement regulations to frame their development and production [2,9]. The decentralization of production, the emergence of new manufacturing platforms, and particularly the conduct of POC manufacture in a large number of hospitals, bring about additional regulatory challenges, as regulatory agencies need to learn to ensure the continued safety, efficacy, and quality of medicinal products manufactured outside centralized facilities.…”