Surveying local CAR T-cell manufacturing processes to facilitate standardization and expand accessibility

Abstract

BACKGROUND: Chimeric antigen receptor T-cell (CAR T-cell) therapies have shown significant promise in treating cancers and other diseases. However, the manufacturing processes for CAR T-cell therapies exhibit considerable variability, which can affect treatment consistency and patient outcomes. While centralized manufacturing models dominate, local decentralized approaches, including point-of-care production, are being explored to address logistical and access challenges. This study aims to evaluate the current landscape of local CAR T-cell manufacturing at academic institutions. METHODS: A comprehensive, cross-sectional survey was distributed to 130 FACT and/or JACIE accredited academic institutions globally. The survey, developed from semi-structured interviews with CAR T-cell manufacturing experts, assessed practices in cell modification methods, equipment protocols, and regulatory challenges. Data were analyzed using descriptive statistics, comparing responses across institutions and regions. RESULTS: 45 of the 130 institutions (35 from the United States and 10 internationally, from the European Union, the United Kingdom, and Australia) responded to the survey (35% response rate). Of the 45 responding institutions, 40 were actively engaged or planning to engage in CAR T-cell production, while five had no plans to initiate manufacturing. Within the 40 institutions engaged in CAR T-cell production, 63% (25/40) reported active manufacturing, while 37% (15/40) were in the process of developing manufacturing capabilities. The most commonly reported barriers to local manufacturing were cost constraints (70%, 28/40), regulatory complexities (70%, 28/40), and facility requirements (57%, 17/40). Variability in product quality was cited by 73% (29/40) of institutions. Equipment costs and the need for specialized training emerged as major challenges, particularly for international institutions. Institutions also highlighted the need for automated platforms, with 60% (24/40) using the Miltenyi CliniMACS Prodigy and 50% (20/40) using the Lonza Cocoon. CONCLUSIONS: This study highlights the widespread adoption of local CAR T-cell manufacturing and the significant variability in production processes across institutions. The findings emphasize the importance of establishing quality control benchmarks and data reporting frameworks to improve product consistency and access to CAR T-cell therapies. Addressing barriers such as cost, infrastructure, and regulatory challenges through standardization efforts and international collaboration could enhance the reproducibility, scalability, and accessibility of CAR T-cell therapies globally.