biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2024-24-4-443-455biopreparat-614Research ArticleКОНТРОЛЬ КАЧЕСТВАQUALITY CONTROLОценка специфической активности препаратов эритропоэтина: современное состояниеPotency evaluation of erythropoietin products: current statushttps://orcid.org/0000-0002-6176-5934ГайдероваЛ. А.GaiderovaL. A.

Гайдерова Лидия Александровна, канд. мед. наук

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

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

8/2 Petrovsky Blvd, Moscow 127051

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

Natalia А. Alpatova, Dr. Sci. (Biol.)

8/2 Petrovsky Blvd, Moscow 127051

alpatova@expmed.ruhttps://orcid.org/0000-0001-7864-8972ЛысиковаС. Л.LysikovaS. L.

Лысикова Светлана Леонидовна, канд. мед. наук

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

Svetlana L. Lysikova, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

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

Гуськов Александр Михайлович

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

Alexander M. Guskov

8/2 Petrovsky Blvd, Moscow 127051

guskov@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

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

8/2 Petrovsky Blvd, Moscow 127051

golovinskaya@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202422122024244443455Copyright © Гайдерова Л.А., Алпатова Н.А., Лысикова С.Л., Гуськов А.М., Головинская О.В., 20242024Гайдерова Л.А., Алпатова Н.А., Лысикова С.Л., Гуськов А.М., Головинская О.В.Gaiderova L.A., Alpatova N.A., Lysikova S.L., Guskov A.M., Golovinskaya O.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/614ВВЕДЕНИЕ

ВВЕДЕНИЕ. Учитывая распространенность применения в клинической практике лекарственных препаратов рекомбинантного эритропоэтина человека (рчЭПО) разных производителей, при оценке их качества по показателю «Специфическая активность» важно гарантировать то, что пациенты получают сопоставимые дозы препаратов. Для гармонизации подходов в определении специфической активности необходимо применение фармакопейных биологических методов анализа и соответствующих стандартных образцов (СО) — международных (МСО) и фармакопейных (ФСО).

ЦЕЛЬ

ЦЕЛЬ. Обобщение сведений о фармакопейных требованиях к оценке специфической активности препаратов рчЭПО, об актуальных СО и биологических методиках (in vivo и in vitro) для оценки специфической активности рчЭПО, а также анализ соответствия требованиям нормативной документации на лекарственные средства рчЭПО, зарегистрированные в Российской Федерации.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Представлена информация об особенностях структуры молекул эритропоэтинов. Профиль гликозилирования, который обусловливает различия в периодах полувыведения и скорости биодеградации препаратов рчЭПО, главным образом влияет на специфическую биологическую активность данных препаратов. Приведены фармакопейные требования к биологическим методам оценки специфической активности in vivo. Обобщены сведения о СО, применяемых для определения активности. Отражены проблемы, связанные с разработкой биологических методик оценки специфической активности in vitro, и изучены возможности их включения в фармакопеи. Проведенный анализ методов определения специфической активности лекарственных средств на основе рчЭПО российского производства позволил заключить, что используемые методы не в полном объеме соответствуют установленным требованиям Государственной фармакопеи Российской Федерации.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Выявлена необходимость разработки и аттестации национального фармакопейного СО для оценки специфической активности рчЭПО с целью обеспечения потребностей производителей российских препаратов в условиях импортозамещения. Для внедрения адекватных методов анализа при оценке качества рчЭПО в соответствии с принципом 3R необходима гармонизация подходов и создание единого документа, регулирующего проведение испытаний специфической активности препаратов рчЭПО.

INTRODUCTION

INTRODUCTION. Given the widespread clinical use of recombinant human erythropoietin (rhEPO) products from different manufacturers, potency assays should ensure that patients receive comparable doses of rhEPO across medicinal products. The harmonisation of approaches to potency testing requires the use of pharmacopoeial bioassays and appropriate international/pharmacopoeial reference standards (RSs).

AIM

AIM. This study aimed to summarise information on pharmacopoeial requirements, relevant RSs, and bioassays (in vivo and in vitro) for the assessment of rhEPO potency, as well as to analyse the pharmacopoeial compliance of manufacturers’ specifications for rhEPO products authorised in Russia.

DISCUSSION

DISCUSSION. This article presents information on the molecular structure of erythropoietin. The glycosylation profile of erythropoietin not only accounts for most of the differences in the half-life and biodegradation rate but also significantly influences the potency of rhEPO products. The authors outlined the pharmacopoeial requirements for potency assays in vivo, summarised the information on RSs for potency determination, characterised the development of potency assays in vitro, and studied the possibility of including in vitro assays in pharmacopoeias. The analysis showed that some potency assays used for rhEPO products manufactured in Russia did not comply with the requirements of the State Pharmacopoeia of the Russian Federation.

CONCLUSIONS

CONCLUSIONS. The study identified the need to develop and certify a national pharmacopoeial RS for the potency of rhEPO in order to satisfy the demands of Russian manufacturers in the context of import substitution. To implement adequate 3R-compliant methods for rhEPO quality assessment, it is necessary to harmonise approaches to potency testing of rhEPO products and develop a consolidated document governing such testing.

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