Identification of the Conditions and Minimum Requirements Necessary for the Release of Autologous Fresh CAR T-cell Products Under Hospital Exemption: a Position Paper from the WP-bioproduction of the UNITC Consortium

The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption. This exemption enables academic institutions to produce ATMPs, including autologous CAR-T cells, under GMP conditions tailored to specific needs. In response to this regulatory framework, our work group has launched a guideline initiative. This endeavor aims to bolster academic CAR T-cell manufacturing by implementing strategic workshops that serve a dual purpose: standardizing production processes and ensuring both efficacy and safety standards are met. This inaugural focused on delineating criteria for the release of fresh CAR-T cell batches. Key emphases included thorough product characterization, stringent safety and potency evaluations. These criteria are essential for compliance with regulatory mandates and aligning with industry best practices. Notably, the release of initial CAR T-cell batches will be facilitated through provisional certification, with final certification contingent upon the acquisition of comprehensive analytical control results. This procedural framework adheres to methodologies endorsed by the SFGM-TC and the EBMT. Such adherence underscores a commitment to harmonizing practices across academic manufacturing facilities, thus fortifying the accessibility, efficacy, and safety of point-of-care units.