The hospital exemption pathway for the approval of advanced therapy medicinal products: an underused opportunity? The case of the CAR-T ARI-0001

Abstract

In February 2021, the 'Advanced Therapy Medicinal Product' (ATMP) ARI-0001 (CART19-BE-01), developed at Hospital Clínic de Barcelona (Spain), received authorization from the Spanish Agency of Medicines and Medical Devices (AEMPS) under the 'hospital exemption' (HE) approval pathway for the treatment of patients aged >25 years with relapsed/refractory (RR) acute lymphoblastic leukemia (ALL). The HE pathway foreseen by the European Regulation establishing the legal framework for ATMPs intended to be placed on the market in the EU, allows access to ATMPs prepared on a non-routine basis, according to quality standards, like a custom-made product for an individual patient. Its use is limited to the same Member State where it was developed, in a hospital under the responsibility of a medical practitioner. HE-ATMPs must comply with national traceability and pharmacovigilance requirements and specific quality standards. HE offers an opportunity to develop ATMPs in close contact with clinical practice, with the quality and rapid access needed by patients and at a lower cost compared to regular market authorization. However, many barriers need to be overcome. Here we discuss relevant aspects of the development and authorization of ARI-0001 in the context of the heterogeneous frame of the European Regulation implementation across the Member States.

Fig. 1. Main deliverables during the ARI-0001 development and authorisation processes and current state.

Under the time line from 1990 to 2021, each square with vertical text show aspects related with the development; the vertical text with a specific date express more relevant milestones in the process; horizontal text inside arrows express main steps of this process. The number of patients in horizontal are located in the general period of the timeline.

Fig. 2. The different font sizes indicate the relative participation in the project.

CRO contract research organization, QC GMP quality control according to good manufacturing practices, ICU intensive care unit, SCTU stem cell transplantation unit.