Advanced therapy medicinal products: Emerging therapeutic frontiers and evolving regulatory landscapes

Advanced Therapy Medicinal Products (ATMPs) are reshaping therapeutic paradigms by enabling disease-modifying and regenerative interventions that address the root causes of pathology. This review explores the scientific, clinical, and regulatory dimensions of ATMPs, focusing on their classification into gene therapy medicinal products (GTMPs), somatic cell therapy medicinal products (sCTMPs), tissue-engineered products (TEPs), and combined ATMPs (cATMPs). While GTMPs and sCTMPs have demonstrated increasing clinical maturity and market penetration, TEPs and cATMPs remain underrepresented despite a substantial scientific foundation in tissue engineering. This discrepancy highlights a critical translational gap likely driven by manufacturing complexity, challenges in mechanism-of-action validation, and regulatory ambiguity. We provide a comparative analysis of the regulatory frameworks in the European Union and the United States, emphasizing how differing classification schemes, definitions of substantial manipulation, and market authorization pathways impact product development. By examining commercial products, scientific principles, and evolving regulatory strategies, this review aims to clarify current trends, identify persistent barriers, and propose directions for harmonizing innovation with clinical and regulatory readiness across all ATMP categories. • Clinical maturity has been reached by GTMPs and sCTMPs, not TEPs or cATMPs. • Translational barriers limit TEPs despite scientific advances. • The EU uses categorical, FDA risk-based ATMP regulation. • Manipulation criteria and combo oversight remain hurdles. • Progress requires adaptive regulation and scalable platforms.