International Regulatory Classification of Minimally Manipulated and Borderline Cell and Tissue Products:...

Cell and tissue products used in regenerative medicine are classified differently across jurisdictions according to processing, intended use, and manufacturing setting. This review compares regulatory approaches to products including bone marrow aspirate concentrate, adipose-derived stromal vascular fraction (SVF), microfragmented adipose tissue, nanofat, amniotic products, and cartilage-derived products, with particular attention to their implications for mesenchymal stromal cell (MSC)-based interventions. Legislation, regulatory guidance, enforcement documents, judicial decisions, and scientific publications were examined for the United States, European Union, Russian Federation, Eurasian Economic Union, selected Asian countries, and Arab jurisdictions. In the United States, minimal manipulation and homologous use are central classification criteria. In the European Union, substantial manipulation or use for a different essential function may bring a product within the advanced therapy medicinal product framework. Russian and Eurasian rules require distinction among biomedical cell products, individualized products, medicinal products, transplantation materials, and medical procedures. SVF is a heterogeneous cell population, while microfragmented adipose tissue retains tissue structures. Neither should be equated with an isolated or culture-expanded MSC preparation solely because it contains stromal cells. Regulatory assessment and interpretation of clinical evidence require clear reporting of product composition, processing, claimed mechanism of action, and manufacturing conditions.