Classification of Cell Therapy Products by Cell Manipulation Degree and Functions Performed: Analysis of International Regulatory Approaches

Abstract

INTRODUCTION. The degree of processing (manipulation) of cells included in a cell product and the functions performed after administration (homologous/non-homologous use) determine the classification of the cell product as a transplant or an advanced therapy medicinal product (ATMP) and, hence, the regulatory aspects of the product’s life cycle. Currently, the legislation of the Eurasian Economic Union (EAEU) and the Russian Federation does not sufficiently explain the terms ‘minimal manipulation’ and ‘homologous/non-homologous use’, which may lead to the use of cell products with unproven safety and efficacy in humans.AIM. This study aimed to compare Russian and international approaches to the interpretation of the terms ‘minimal manipulation’ and ‘homologous/non-homologous use’ for classifying cell products and determining their regulatory pathways, with stromal vascular fraction (SVF) products used as an example.DISCUSSION. This article reviews and summarises the regulatory approaches of the Russian Federation, the EAEU, the United States (US), and the European Union (EU) that are based on the classification of cell products according to the degree of cell manipulation and the functions performed after administration. The authors have analysed and compared the regulatory acts and approaches of the countries under consideration, with SVF products as a case study. The article highlights general aspects of interpreting the terms ‘minimal manipulation’ and ‘homologous/ non-homologous use’ and demonstrates the difference in regulatory approaches across several countries, which lies in the classification of enzymatic processing and selective collection of cells as substantial or minimal manipulation.CONCLUSIONS. The mechanism for regulating cell products depends on the degree of cell manipulation (substantial or minimal) and the intended use (homologous or non-homologous). A common principle adopted by regulatory agencies in the US, EU, EAEU, and Russia is to classify manipulation as minimal if the manipulated cells preserve their biological characteristics and physiological function. A defining characteristic of the homologous use of cells or tissues is their administration to perform their inherent functions in the body. In Russia, the regulatory acts for ATMPs and for transplants list the procedures classified as minimal manipulation. According to international standards, preparations based on minimally manipulated SVF cells are classified as ATMPs when used non-homologously. The lack of comprehensive and clear explanations of the terms ‘minimal manipulation’ and ‘homologous/non-homologous use’ in the legislation of the EAEU and the Russian Federation necessitates the development of relevant guidelines providing specific examples.