safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2025-13-2-229-240safetyrisk-496Research ArticleТРАНСЛЯЦИОННАЯ МЕДИЦИНА: ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ, РЕГЕНЕРАТИВНАЯ ТЕРАПИЯ И ПРИНЦИПЫ 3RTRANSLATIONAL MEDICINE: PRECLINICAL STUDIES, REGENERATIVE THERAPY, AND THE 3R PRINCIPLESРеализация концепции 3Rs при контроле качества биологических препаратов: современное состояние и перспективы (обзор)Implementation of the 3Rs Concept in Quality Control of Biologicals: Status and Prospects (Review)https://orcid.org/0000-0002-6176-5934ГайдероваЛ. А.GaiderovaL. A.

Гайдерова Лидия Александровна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Lidia A. Gaiderova, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

Gaiderova@expmed.ruhttps://orcid.org/0000-0002-6807-508XАлпатоваН. А.AlpatovaN. A.

Алпатова Наталья Александровна, д-р биол. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Natalia А. Alpatova, Dr. Sci. (Biol.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

alpatova@expmed.ruhttps://orcid.org/0000-0002-6966-9859ГоловинскаяО. В.GolovinskayaO. V.

Головинская Ольга Вячеславовна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Olga V. Golovinskaya, Cand. Sci. (Med.) 

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

golovinskaya@expmed.ruhttps://orcid.org/0000-0003-4523-5316ГуськовА. М.GuskovA. M.

Гуськов Александр Михайлович

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Alexander M. Guskov

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

guskov@expmed.ruhttps://orcid.org/0000-0003-1471-8737ЛипатоваЭ. К.LipatovaE. K.

Липатова Эльвира Константиновна

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Elvira K. Lipatova

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

https://orcid.org/0009-0001-2197-378XЛавроваМ. Н.LavrovaM. N.

Лаврова Марина Николаевна, канд. фарм. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация

Marina N. Lavrova, Cand. Sci. (Pharm.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

lavrovamn@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medical ProductRussian Federation202524062025132229239Copyright © Гайдерова Л.А., Алпатова Н.А., Головинская О.В., Гуськов А.М., Липатова Э.К., Лаврова М.Н., 20252025Гайдерова Л.А., Алпатова Н.А., Головинская О.В., Гуськов А.М., Липатова Э.К., Лаврова М.Н.Gaiderova L.A., Alpatova N.A., Golovinskaya O.V., Guskov A.M., Lipatova E.K., Lavrova M.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/496

ВВЕДЕНИЕ. В рамках концепции «Replacement, reduction and refinement of animal testing» (3Rs) во многих странах увеличивается количество альтернативных методов без использования животных для исследовательских целей, разработки и контроля качества лекарственных средств. Однако внедрение в перечень испытаний альтернативных методов in vitro вместо методов in vivo при выпуске новых серий биологических лекарственных препаратов, в первую очередь вакцин, является сложной задачей. Процесс интеграции принципов 3Rs в регуляторные и производственные стандарты требует анализа, в том числе с учетом специфики национальных систем.ЦЕЛЬ. Анализ степени интегрированности принципов 3Rs в процесс контроля качества биологических лекарственных средств в мировой практике и оценка существующих препятствий и возможностей для успешной реализации перехода к контролю качества препаратов без применения животных в Российской Федерации.ОБСУЖДЕНИЕ. К основным преимуществам биологических методов in vitro по сравнению с in vivo при контроле качества препаратов относятся меньшая вариабельность, более высокая специфичность, сокращение сроков проведения испытаний. Анализ результатов оценки регуляторными органами и производителями лекарственных средств возможностей и препятствий при реализации концепции 3Rs выявил основные аргументы при замене методов in vivo: этический аспект, актуальность сокращения времени тестирования, снижение вариабельности. Интеграция методов in vitro сдерживается недостаточностью информации об альтернативных методах, а также отсутствием гармонизации нормативной базы по внедрению 3Rs. На примере внедрения принципов 3Rs в Европейскую фармакопею показано исключение всех общих испытаний по оценке безопасности биологических лекарственных средств на животных. Всемирной организацией здравоохранения разработано руководство по поэтапному отказу от испытаний на животных для контроля качества биологических продуктов.ВЫВОДЫ. Основные проблемы интеграции принципов 3Rs заключаются в сложности подтверждения корреляции между методами in vivo и in vitro, в том числе при проведении однозначного сравнения указанных методов, отсутствии гармонизации требований регуляторных органов, а также содействия последних производителям в принятии альтернативных методов. Международная гармонизация нормативных требований необходима для эффективного решения обозначенных проблем и успешного внедрения 3Rs в процедуры контроля качества биологических лекарственных препаратов при выпуске в разных странах, включая Российскую Федерацию.

INTRODUCTION. Many countries are implementing an increasing number of alternatives to animal testing in the research, development, and quality control of medicines under the concept of 3Rs (replacement, reduction, and refinement). However, the implementation of in vitro alternatives to in vivo methods into batch release testing of biologicals, primarily vaccines, is a challenging process. The introduction of the 3Rs principles into regulatory and industry standards requires a comprehensive analysis, including, among other things, a study of specific considerations for national frameworks.AIM. This study aimed to analyse the degree of global integration of the 3Rs principles in the quality control of biological medicinal products and to assess existing challenges and opportunities for a successful transition to non-animal quality control methods in the Russian Federation.DISCUSSION. The key advantages of in vitro biological methods over in vivo approaches for quality control of medicinal products include reduced variability, higher specificity, and shorter testing timelines. Analysis of assessments by regulatory authorities and pharmaceutical manufacturers regarding the opportunities and challenges in implementing the 3Rs principles has identified the following main arguments for replacing in vivo methods: ethical considerations, relevance of reducing testing time, decreased variability. The integration of in vitro methods is hindered by insufficient information on alternative approaches and the lack of harmonised regulatory frameworks for adopting 3Rs principles. For instance, the European Pharmacopoeia has eliminated all general safety testing of biological medicinal products in animals as part of its 3Rs implementation. Furthermore, the World Health Organization has developed guidelines for the phased discontinuation of animal testing in the quality control of biological products.CONCLUSIONS. The main challenges associated with 3Rs implementation include the difficulty of confirming the in vitro – in vivo correlation (particularly, by comparing in vivo and in vitro methods), the lack of regulatory harmonisation, and the insufficient regulatory support for manufacturers in adopting alternative methods. The international harmonisation of regulatory requirements is necessary to effectively address these issues and successfully implement the 3Rs principles in the quality control procedures for biologicals released in different countries, including the Russian Federation.

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The authors declare that there are no conflicts of interest present.