Problems of Social Hygiene, Public Health and History of MedicineProblems of Social Hygiene, Public Health and History of Medicine0869-866X2412-2106Joint-Stock Company Chicot38310.32687/0869-866X-2020-28-5-883-892Научная статьяIs the health care system ready to apply gene therapy preparations?OmelianovskyV. V.-MusinaN. Z.-LemeshkoV. A.lera.lemeschko@yandex.ruGorkavenkoF. V.-AntonovA. A.-The Russian Academy of National Economy and Government Service under the President of the Russian FederationThe Federal State Budget Institution “The Center of Expertise and Control of Quality of Medical Care” of Minzdrav of RussiaThe Federal State Budget Educational Institution of Higher Education “The St. Petersburg State Chemical Pharmaceutical University” of Minzdrav of RussiaThe Federal State Autonomous Educational Institution of Higher Education “The I. M. Sechenov First Moscow State Medical University” of Minzdrav of RussiThe Federal State Budget Institution “The Research Financial Institute” of the Minfin of Russia1512202028588389206042021Copyright © 2020,2020The gene therapy is totally new approach to treatment of patient. It has significant therapeutic potential for wide range of diseases, including those caused by genetic disorders. The in vivo therapy is one of types of gene therapy meaning that impact on gene apparatus of somatic cells occurs straight within organism of patient. Among significant advantages of of this kind of therapy is potential opportunity of treatment of diseases which previously had no effective therapy or only supportive symptomatic therapy was administered. The article describes international approaches to classification of gene therapy preparations. The review of in vivo gene therapy preparations currently registered in different countries. Also, the features of their development, production and registration are analyzed. For many in vivo gene therapy preparations, due to small number of patients, clinical evidence base is limited, especially in terms of long-term clinical effect that complicates process of registration and economic evaluation for subsequent their inclusion in the system of state funding. It should also be noted that gene preparations currently registered abroad have extremely high cost that limits their widespread implementation into clinical practice. The production of gene therapy preparations requires a number of additional measures targeted to supporting product quality that complicates process of their production and registration. Due to absence of necessity in large production capacities, gene therapy preparations are produced centrally that results in their logistic complexities. It is actual to analyze international experience of distribution of in vivo gene therapy preparations in order to optimize approaches to regulation, assessment and financing of gene technologies in the Russian Federation.in vivo gene therapynormative legislative regulationdevelopment of medicinal preparationsproduction of medicinal preparationsregistration of medicinal preparationsreviewгенная терапия in vivoнормативно-правовое регулированиеразработка лекарственных препаратовпроизводство лекарственных препаратоврегистрация лекарственных препаратовобзор1.Halioua-Haubold C. L., Peyer J. G., Smith J. A., Arshad Z., Scholz M., Brindley D. A., MacLaren R. E. Regulatory considerations for gene therapy products in the US, EU, and Japan. Yale J. Biol. Med. 2017;90(4):683-93.2.European Medicines Agency. Reflection paper on classification of advanced therapy medicinal products. 2015. Режим доступа: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-classification-advanced-therapy-medicinal-products_en-0.pdf3.Therapeutic Goods Administration, Guidance 21: Medicines produced by genetic manipulation. V1.0; 2013.4.Official Journal of the European Union. REGULATION (EC) No 1394/2007. On advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. 2007.5.European Parliament. Directive 2001/83/EC of The European parliament and of the council of 6 November 2001 on the Community code relating to medicinal products for human use. 2001;188.6.Shukla V., Seoane-Vazquez E., Fawaz S., Brown L. M., Rodriguez-Monguio R. The landscape of cellular and gene therapy products: cost, approvals, and discontinuations. Hum. Gene. Ther. Clin. Dev. 2019;30(3):102-13. doi: 10.1089/humc.2018.2017.Sinclair A., Islam S., Jones S. Gene Therapy: An Overview of Approved and Pipeline Technologies. CADTH Issues in Emerging Health Technologies. Canadian Agency for Drugs and Technologies in Health; 2018.8.Anguela X. M., High K. A. Entering the modern era of gene therapy. Ann. Rev. Med. 2019;70:273-88.9.Maeder M. L., Stefanidakis M., Wilson C. J., Baral R., Barrera L. A., Bounoutas G. S. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat. Med. 2019;25(2):229-33.10.Philippidis A. Top 10 Companies Leveraging Gene Editing in 2018. Available at: https://www.genengnews.com/a-lists/top-10-companies-leveraging-gene-editing/11.Miniarikova J., Zimmer V., Martier R., Brouwers C. C., Pythoud C., Richetin K. AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington’s disease. Gene Ther. 2017;24(10):630-9.12.Carvalho M., Sepodes B., Martins A. P. Regulatory and scientific advancements in gene therapy: state-of-the-art of clinical applications and of the supporting European regulatory framework. Front. Med. 2017;4:182.13.Athanasopoulos T., Munye M. M., Yanez-Munoz R. J. Nonintegrating gene therapy vectors. Hematol. Clin. 2017;31(5):753-70.14.Li W., Asokan A., Wu Z., Van Dyke T., DiPrimio N., Johnson J. S. Engineering and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Mol. Ther. 2008;16(7):1252-60.15.Coppens D. G. M., de Wilde S., Guchelaar H. J., De Bruin M. L., Leufkens H. G. M., Meij P., Hoekman J. A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making. Cytotherapy. 2018;20(6):769-78.16.Hampson G., Towse A., Pearson S. D., Dreitlein W. B., Henshall C. Gene therapy: evidence, value and affordability in the US health care system. J. Comparat. Effect. Res. 2018;7(1):15-28.17.Azuma K. Regulatory landscape of regenerative medicine in Japan. Curr. Stem. Cell Rep. 2015;1(2):118-28.18.European Commission. Assessment of the function of the Clinical Trials directive 2001-20-EC 2009_10_09 Public-consultation-paper. Eur. Commis. J. 2009;4:1-32.