Orthogonal approach and critical quality attributes for gene and cell therapy products
Авторы
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Екатерина В. Мельникова
Научный центр экспертизы средств медицинского применения Минздрава России
https://orcid.org/0000-0002-9585-3545
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Марина A. Водякова
Научный центр экспертизы средств медицинского применения Минздрава России
https://orcid.org/0000-0002-9585-3545
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Никита С. Покровский
Научный центр экспертизы средств медицинского применения Минздрава России
https://orcid.org/0000-0002-2355-0879
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Вадим A. Меркулов
Научный центр экспертизы средств медицинского применения Минздрава России
https://orcid.org/0000-0003-4891-973X
DOI:
https://doi.org/10.18413/rrpharmacology.11.738Аннотация
Introduction: Gene and cell therapy (GCT) products are revolutionizing medicine because they are made up of unique biological components like genetic material, viral vectors, and viable cells. However, their complexity necessitates rigorous quality control strategies to ensure efficacy, safety, and batch consistency. This manuscript explores the application of an orthogonal approach – employing multiple independent methods – to assess critical quality attributes, such as identity, potency, and purity of GCT products.
Materials and Methods: To achieve the aim of our work, we analyzed 15 GCT products for 11 different types of diseases and reports of multiple regulatory agencies.
Results: For cell-based therapies, identity is confirmed through genotypic, phenotypic, and morphological analyses, while potency is evaluated using functional assays tailored to the product’s mechanism of action, such as cell viability, differentiation status, or cytokine secretion. Viral vector-based therapies require characterization of structural integrity, transgene expression, and the ratio of full to empty capsids, employing techniques like dynamic light scattering (DLS), PCR, and ELISA.
Conclusion: The paper highlights regulatory recommendations from the FDA, EMA, and WHO, emphasizing the need for validated assays during product release and stability testing. Case studies, including CAR-T cells and AAV-based therapies, illustrate the practical implementation of orthogonal methods. Challenges such as assay variability and the need for clinical correlation are discussed, underscoring the importance of assay development early in the product lifecycle. By integrating diverse analytical techniques, the orthogonal approach ensures comprehensive product characterization facilitating the translation of GCTs from research to clinical application.
Графическая аннотация
Ключевые слова:
orthogonal approach, quality attributes, quality control, cell therapy, gene therapyБиблиографические ссылки
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