Specific aspects and key parameters of validation for methods of phenotyping of cell lines included in cell therapy products
AbstractThe authenticity (identity) of cell lines (cells) is one of the most important quality indicators of medicinal products containing viable human cells. Immunophenotypic characterization of human cells is fundamental to the identification of a cell therapy product before its clinical application. The most widely used method for phenotyping cell lines is flow cytometry. The study is devoted to the analysis of the specific aspects of cell line phenotyping methods validation. This study reviewed key parameters of the method validation process, as well as current data on validation specific aspects related to cell therapy products, reagents and equipment used, rare events and compensation.
Keywords:validation; phenotyping; flow cytometry; quality control; cell lines
For citation: Pokrovsky N.S., Vodyakova M.A., Merkulov V.A., Melnikova E.V. Specific aspects and key parameters of validation for methods of phenotyping of cell lines included in cell therapy products. Immunologiya. 2024; 45 (3): 343–54. DOI: https://doi.org/10.33029/1816-2134-2024-45-3-343-354 (in Russian)
Funding. The study reported in this publication was carried out as part of publicly funded research project No. 05600026-24-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products, Ministry of Health of the Russian Federation (R&D public accounting 124022200093-9). Open publication of the research results is allowed.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. Writing the text, collection and processing of material – Pokrovsky N.S., Vodyakova M.A.; editing – Merkulov V.A.; the concept and design of the study – Melnikova E.V.
References
1. Trusov G.A., Chaplenko A.A., Semenova I.S., Melnikova E.V., Olefir Yu.V. Use of Flow Cytometry for Quality Evaluation of Biomedical Cell Products. Biopreparaty Profilaktika, diagnostika, lechenie. 2018; 18 (1): 16–24. DOI: https://doi.org/10.30895/2221-996X-2018-18-1-16-24 (in Russian)
2. Lambert C., Yanikkaya D. G., Keller T., Preijers F., Psarra K., Schiemann M., Özçürümez M., Sack U. Flow Cytometric Analyses of Lymphocyte Markers in Immune Oncology: A Comprehensive Guidance for Validation Practice According to Laws and Standards. Front Immunol. 2020; 11: 2169. DOI: https://doi.org/10.3389/fimmu.2020.02169
3. O’Hara D.M., Xu Y., Liang Z., Reddy M.P., Wu D.Y., Litwin V. Recommendations for the validation of flow cytometric testing during drug development: II assays. Journal of Immunological Methods. 2011; 363 (2): 120–34. DOI: https://doi.org/10.1016/j.jim.2010.09.036
4. Viganò M., Budelli S., Lavazza C., Montemurro T., Montelatici E., De Cesare S., Lazzari L., Orlandi A.R., Lunghi G., Giordano R. Tips and Tricks for Validation of Quality Control Analytical Methods in Good Manufacturing Practice Mesenchymal Stromal Cell Production. Stem Cells International. 2018; 2018: 1–16. DOI: https://doi.org/10.1155/2018/3038565
5. Davis B.H., Wood B., Oldaker T., Barnett D. Validation of cell-based fluorescence assays: Practice guidelines from the ICSH and ICCS – part I – rationale and aims. Cytometry Part B: Clinical Cytometry. 2013; 84 (5): 282–5. DOI: https://doi.org/10.1002/cyto.b.21104
6. Davis B.H., Dasgupta A., Kussick S., Han J.Y., Estrellado A. Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS – part II – preanalytical issues. Cytometry Part B: Clinical Cytometry. 2013; 84 (5): 286–90. DOI: https://doi.org/10.1002/cyto.b.21105
7. Tangri S., Vall H., Kaplan D., Hoffman B., Purvis N., Porwit A., Hunsberger B., Shankey T.V. Validation of cell-based fluorescence assays: Practice guidelines from the ICSH and ICCS – part III – analytical issues. Cytometry Part B: Clinical Cytometry. 2013; 84 (5): 291–308. DOI: https://doi.org/10.1002/cyto.b.21106
8. Barnett D., Louzao R., Gambell P., De J., Oldaker T., Hanson C.A. Validation of cell-based fluorescence assays: Practice guidelines from the ICSH and ICCS – part IV – postanalytic considerations. Cytometry Part B: Clinical Cytometry. 2013; 84 (5): 309–14. DOI: https://doi.org/10.1002/cyto.b.21107
9. Wood B., Jevremovic D., Béné M.C., Yan M., Jacobs P., Litwin V. Validation of cell-based fluorescence assays: Practice guidelines from the ICSH and ICCS – part V – assay performance criteria. Cytometry Part B: Clinical Cytometry. 2013; 84 (5): 315–23. DOI: https://doi.org/10.1002/cyto.b.21108
10. CLSI. H62. Validation of Assays Performed by Flow Cytometry. 1st ed. 2021. 234 p. ISBN: 978-1-68440-128-4.
11. Lee J.W., Devanarayan V., Barrett Y.C., Weiner R., Allinson J., Fountain S., Keller S., Weinryb I., Green M., Duan L., Rogers J.A., Millham R., O’Brien P.J., Sailstad J., Khan M., Ray C., Wagner J.A. Fit-for-Purpose Method Development and Validation for Successful Biomarker Measurement. Pharm Res. 2006; 23 (2): 312–28. DOI: https://doi.org/10.1007/s11095-005-9045-3
12. European Medicines Agency (EMA). ICH Topic Q2 (R2) Validation of Analytical Procedures: Text and Methodology. 2023. URL: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q2r2-guideline-validation-analytical-procedures-step-5-revision-1_en.pdf
13. The Ministry of Health of the Russian Federation. The State Pharmacopoeia of the Russian Federation XV edition. OFS.1.1.0012 «Validation of analytical techniques». 2023. URL: https://pharmacopoeia.regmed.ru/pharmacopoeia/izdanie-15/1/1-1/validatsiya-analiticheskikh-metodik/ (in Russian)
14. Selliah N., Nash V., Eck S., Green C., Oldaker T., Stewart J., Vitaliti A., Litwin V. Flow Cytometry Method Validation Protocols. Current Protocols. 2023; 3 (8): e868. DOI: https://doi.org/10.1002/cpz1.868
15. Sommer U., Eck S., Marszalek L., Stewart J.J., Bradford J., McCloskey T.W., Green C., Vitaliti A., Oldaker T., Litwin V. High-sensitivity flow cytometric assays: Considerations for design control and analytical validation for identification of Rare events. Cytometry Part B Clinical. 2021; 100 (1): 42–51. DOI: https://doi.org/10.1002/cyto.b.21949
16. CLSI. H42. Enumeration of Immunologically Defined Cell Populations by Flow Cytometry. 2nd ed. 2007. 88 p. ISBN: 1-56238-640-9.
17. Vodyakova M.A., Pokrovsky N.S., Melnikova E.V., Merkulov V.A. Recommendations for Validation of Automated Viable Cell Counting Methods (Review). Drug development & registration. 2023; 12 (4): 217–22. DOI: https://doi.org/10.33380/2305-2066-2023-12-4-1424
18. Donnenberg A.D., Donnenberg V.S. Rare-Event Analysis in Flow Cytometry. Clinics in Laboratory Medicine. 2007; 27 (3): 627–52. DOI: https://doi.org/10.1016/j.cll.2007.05.013
19. Khaidukov S.V. Approaches to standardization of the flow cytometry method for cells immunophenotiping. Cytometrs adjustment and preparation of protocols for analysis. Med immunol. 2014; 9 (6): 569. DOI: https://doi.org/10.15789/1563-0625-2007-6-569-574 (in Russian)