biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2024-24-3-335-347biopreparat-613Research ArticleКОНТРОЛЬ КАЧЕСТВАQUALITY CONTROLОбзор современных регуляторных требований к изучению стабильности биологических лекарственных препаратовCurrent regulatory requirements for stability studies of biological medicinal products: a reviewhttps://orcid.org/0000-0001-6624-2692СолдатовА. А.SoldatovA. A.

Солдатов Александр Алексеевич, д-р мед. наук

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

Aleksandr A. Soldatov, Dr. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

soldatov@expmed.ruhttps://orcid.org/0000-0002-2809-1819ЯковлевА. К.YakovlevA. K.

Яковлев Алексей Константинович, канд. биол. наук

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

Aleksey K. Yakovlev, Cand. Sci. (Biol.)

8/2 Petrovsky Blvd, Moscow 127051

yakovlev@expmed.ruhttps://orcid.org/0000-0002-9377-1378АвдееваЖ. И.AvdeevaZh. I.

Авдеева Жанна Ильдаровна, д-р мед. наук, проф.

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

Zhanna I. Avdeeva, Dr. Sci. (Med.), Prof.

8/2 Petrovsky Blvd, Moscow 127051

Avdeeva@expmed.ruhttps://orcid.org/0000-0003-0940-8080ГоренковД. В.GorenkovD. V.

Горенков Дмитрий Витальевич

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

Dmitry V. Gorenkov

8/2 Petrovsky Blvd, Moscow 127051

diyarl@ya.ruhttps://orcid.org/0000-0002-3241-1053КоровкинА. С.KorovkinA. S.

Коровкин Алексей Сергеевич, канд. мед. наук

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

Alexey S. Korovkin, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

korovkinas@expmed.ruhttps://orcid.org/0000-0001-8353-7863КосенкоВ. В.KosenkoV. V.

Косенко Валентина Владимировна, канд. фарм. наук

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

Valentina V. Kosenko, Cand. Sci. (Pharm.)

8/2 Petrovsky Blvd, Moscow 127051

kosenko@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202404102024243Разработка диагностических, лечебных и профилактических препаратов противовирусного действия335347Copyright © Солдатов А.А., Яковлев А.К., Авдеева Ж.И., Горенков Д.В., Коровкин А.С., Косенко В.В., 20242024Солдатов А.А., Яковлев А.К., Авдеева Ж.И., Горенков Д.В., Коровкин А.С., Косенко В.В.Soldatov A.A., Yakovlev A.K., Avdeeva Z.I., Gorenkov D.V., Korovkin A.S., Kosenko V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/613ВВЕДЕНИЕ

ВВЕДЕНИЕ. Для оценки стабильности биологических лекарственных препаратов (БЛП) требуются особые подходы и нормативные требования. В связи с этим необходима разработка актуальных национальных рекомендаций для препаратов данной группы, что является важным условием их безопасного и эффективного использования.

ЦЕЛЬ

ЦЕЛЬ. Анализ национальных и международных требований к оценке стабильности биологических лекарственных препаратов для последующего обоснования единого регуляторного подхода к определению и подтверждению срока годности препаратов.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Большинство биотехнологических лекарственных препаратов (БТЛП), учитывая их белковую природу, характеризуются высокой чувствительностью к действию факторов внешней среды, в связи с чем срок годности БТЛП устанавливается на осно ве результатов исследования стабильности, полученных в условиях реального времени. Оценка стабильности в ускоренных и стрессовых условиях используется для обоснования срока годности, а также для характеристики механизма деградации структуры белка, что позволяет выбрать наиболее чувствительные показатели и методы анализа при проведении исследований стабильности. Национальными и международными регуляторными органами разработаны специализированные руководства по исследованию стабильности БЛП различного происхождения. В регуляторной системе Евразийского экономического союза (ЕАЭС) разработаны подходы к оценке стабильности, гармонизированные с международными стандартами. Особенности изучения стабильности вакцин подразумевают, помимо установления срока годности, также определение стабильности восстановленных для применения препаратов и термостабильности при кратковременных нарушениях температурного режима «холодовой цепи».

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Испытания стабильности различных групп БЛП (включая биотехнологические и иммунобиологические) имеют свои особенности, что диктует необходимость разработки и совершенствования системы требований к оценке стабильности. Это позво лит оптимизировать процессы обращения БЛП в Российской Федерации и на территории государств — членов ЕАЭС.

INTRODUCTION

INTRODUCTION. The stability assessment of biological medicinal products (BMPs) requires special approaches and regulatory requirements. Therefore, BMPs require relevant national guidelines, which are an important prerequisite for the assurance of the safe and effective use of BMPs.

AIM

AIM. This study aimed to analyse national and international requirements for the stability assessment of BMPs in order to use the results to inform future development of a unified regulatory approach to estimating and confirming shelf-life periods for BMPs.

DISCUSSION

DISCUSSION. Most biotechnological medicinal products (BTMPs) are proteins and are highly sensitive to environmental factors by nature. Therefore, the shelf life of a BTMP is established on the basis of real-time stability studies. Stability testing under accelerated and stress conditions is conducted to support shelf-life claims and to characterise the mechanism of protein structure degradation. The results of accelerated and stress studies can be used to select the most sensitive stability-indicating parameters and testing methods. National and international regulatory authorities have developed specialised guidelines for stability studies of BMPs of various origins, and the stability assessment approaches in the regulatory system of the Eurasian Economic Union (EAEU) are harmonised with international standards. Special considerations associated with the stability of vaccines imply that stability studies of vaccines should not only establish shelf life but also investigate stability after reconstitution and after short-term temperature excursions from the recommended cold-chain conditions.

CONCLUSIONS

CONCLUSIONS. Special stability testing considerations for various groups of BMPs (including BTMPs and immunobiologicals) indicate the need to develop and improve the system of requirements for BMP stability assessment. This will facilitate the optimisation of the life cycle of BMPs in the Russian Federation and the other EAEU member states.

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