Quality control programmes for induced pluripotent stem cell-derived medicinal products

INTRODUCTION. Currently, there are no harmonised regulatory requirements for the quality control of human somatic cell therapy and tissue-engineered medicinal products that contain differentiated cells derived from induced pluripotent stem cells (iPSCs). This lack of uniform requirements underscores the need for approaches to developing quality control programmes and establishing critical quality attributes for iPSC-derived medicinal products within the Eurasian Economic Union (EAEU) regulatory framework.

AIM. This study aimed to systematise global regulatory experience and EAEU regulatory requirements for the development and justification of quality control programmes for iPSC-derived medicinal products.

DISCUSSION. Medicinal products derived from iPSCs are mainly used in the treatment of neurodegenerative, cardiovascular, and oncological diseases, diabetes, graft-versus-host disease, and eye diseases. Over the past decade, specific recommendations and requirements for the quality of clinical-grade iPSCs have been published by the Chinese Society for Stem Cell Research (CSSCR), the Japanese Ministry of Health, Labour, and Welfare (MHLW), the Global Alliance for iPSC Therapy (GAiT), and the European Bank of iPSC (EBiSC). The EAEU regulatory requirements for the quality of genetically modified cells have been in effect since 2025 (Chapter 32 of Decision No. 89 of the Council of the Eurasian Economic Commission “On Approval of the Rules for Assessment of Biological Medicines in the EAEU” of November 3, 2016). The list of critical quality attributes for clinical-grade iPSCs proposed by the GAiT generally corresponds to the EAEU regulatory framework and can be used in drawing up quality control programmes for iPSC-derived medicinal products in the Russian Federation and the EAEU. Quality control programmes for finished somatic cell therapy or tissue-engineered medicinal products derived from iPSCs should be based on the principle of quality attribute traceability from the starting material onwards. The production of iPSCs is a full-fledged production process that must comply with Good Manufacturing Practice (GMP) requirements for genetically modified cells. Specific quality controls for iPSCs should include tests for residual reprogramming vector DNA, markers of the undifferentiated state, and pluripotency as part of purity characterisation, identification, and potency evaluation, respectively.

CONCLUSIONS. A quality control programme for a finished iPSC-derived medicinal product should correspond to the type of differentiated cells and take into account the indications for use. Critical quality considerations for iPSC characterisation include demonstrating the absence of contaminating undifferentiated cells or cells with new immunogenic epitopes and confirming the identity and genetic stability of iPSCs. The considered quality assessment approaches provide a basis for developing both quality control strategies for iPSC-derived medicinal products and specifications for marketing authorisation according to the EAEU requirements.

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