Decentralized CAR-T manufacturing: highlighting regulatory pathways in the United States and abroad

Regulators worldwide are increasingly evaluating how decentralized and point-of-care (POC) manufacturing models can be integrated into existing frameworks for cell and gene therapies, including chimeric antigen receptor T-cell (CAR-T) therapies. These models challenge traditional centralized production by distributing manufacturing across several clinical or academic sites, requiring new approaches to ensure product consistency, traceability, and Good Manufacturing Practice (GMP) compliance. Across jurisdictions, regulators are converging on several common themes. First, decentralization must operate under a unified quality management system with clearly defined oversight, typically anchored by a central “control” or coordinating site responsible for governance, batch oversight, and harmonized procedures. Second, comparability across sites is critical, necessitating standardized processes, validated technologies, and robust data systems to support real-time quality monitoring. Third, regulators emphasize that decentralized models do not reduce GMP requirements; rather, they require additional structures to ensure alignment across distributed facilities. Many authorities are exploring mechanisms to clarify roles and responsibilities within POC networks, including oversight, documentation standards, and expectations for training, inspection, and data integrity. Some regulators are also assessing how existing pathways such as hospital exemptions, accelerated approval mechanisms, or special designations, could support early clinical use while maintaining rigorous safety and quality controls. In parallel, discussion papers, stakeholder consultations, and emerging guidance reflect a shared interest in addressing technological advances such as automated, closed-system manufacturing. In this article, we review and discuss work being done in this regard across Europe, Canada, and the United States.