vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2025-15-1-44-56vedomostiregmed-733Research ArticleБИОТЕХНОЛОГИЧЕСКИЕ ЛЕКАРСТВЕННЫЕ ПРЕПАРАТЫBIOTECHNOLOGICAL MEDICINAL PRODUCTSЭкспертная оценка определения специфической активности препаратов моноклональных антител биологическим методом in vitroExpert Assessment of In Vitro Potency Assays for Monoclonal Antibody Preparationshttps://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/0000-0002-6966-9859ГоловинскаяО. 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.ruhttps://orcid.org/0000-0001-9889-4038БайковаМ. Л.BaykovaM. L.

Байкова Марина Леонидовна

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

Marina L. Baykova

8/2 Petrovsky Blvd, Moscow 127051

https://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

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

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

8/2 Petrovsky Blvd, Moscow 127051

Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation2025310120251514456Copyright © Алпатова Н.А., Головинская О.В., Байкова М.Л., Лысикова С.Л., Гайдерова Л.А., 20252025Алпатова Н.А., Головинская О.В., Байкова М.Л., Лысикова С.Л., Гайдерова Л.А.Alpatova N.A., Golovinskaya O.V., Baykova M.L., Lysikova S.L., Gaiderova L.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/733ВВЕДЕНИЕ

ВВЕДЕНИЕ. В целях контроля качества биотехнологических лекарственных препаратов используется ряд биологических методик. Разработка методик определения специфической активности препарата представляет собой сложную процедуру, которая должна отвечать рекомендациям регуляторных нормативных документов, а для адекватного воспроизведения таких методик необходимо их корректное представление в проекте нормативной документации на лекарственный препарат.

ЦЕЛЬ

ЦЕЛЬ. Обобщение рекомендаций по разработке и описанию в проекте нормативной документации биологических методик in vitro для определения активности лекарственных средств на основе моноклональных антител.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Описаны Fab- и Fc-ассоциированные механизмы проявления биологической активности препаратов моноклональных антител (моно- и би­специфических), рассмотрены in vivo и in vitro методы изучения указанных механизмов, акцент сделан на анализе репортерного гена. Сформулировано понятие о целостной аналитической системе, необходимой при разработке биологических методик, и проанализированы ее составляющие. Показано, что методика с надежным дизайном позволяет минимизировать влияние критических факторов на результат и снизить риск возникновения случайных и систематических ошибок. Оценена значимость детального отражения критических параметров методики в проекте нормативной документации на лекарственные препараты моноклональных антител.

ВЫВОДЫ

ВЫВОДЫ. Биологические методики определения активности должны отражать механизм действия лекарственного препарата, а также обладать наименее возможной вариабельностью и наиболее возможной простотой воспроизведения. Адекватность методики и правильно подобранные условия ее применения обеспечивают снижение риска получения недостоверных результатов при контроле качества лекарственного препарата.

INTRODUCTION

INTRODUCTION. The quality control of biotechnological medicinal products requires a range of biological assay procedures. The development of bioassays for potency determination is a complex process that should comply with the requirements set forth in regulatory standards. For adequate reproducibility, bioassays should be properly described in draft product specification files.

AIM

AIM. This study aimed to summarise the recommendations for developing in vitro bioassays for potency determination of monoclonal antibody preparations and for describing these bioassays in product specification files.

DISCUSSION

DISCUSSION. This article describes the Fab- and Fc-associated biological activi­ty mechanisms of monospecific and bispecific monoclonal antibodies. The article covers in vivo and in vitro methods used to study these mechanisms, with emphasis on the reporter gene assay. The article formulates the concept and analyses the components of a holistic analytical system that is necessary for bioassay development. A well-designed analytical procedure can minimise the influence of critical factors on the test results and reduce the risks of both random and systematic errors. This article presents an estimation of the significance of detailed description of critical procedure parameters in the draft product specification file for a monoclonal antibody.

CONCLUSIONS

CONCLUSIONS. A bioassay for the determination of potency should reflect the mecha­nism of action of the medicinal product and should provide the lowest possible variability and the highest possible ease of use. An adequate analytical procedure with appropriate analytical conditions can reduce the risk of obtaining invalid quality control results.

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