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’)10.30895/1991-2919-2026-16-2-179-189vedomostiregmed-845Research ArticleГЛАВНАЯ ТЕМА: ГАРМОНИЗАЦИЯ ФАРМАКОПЕЙНЫХ СТАНДАРТОВ: ОПЫТ РОССИЙСКОЙ ФЕДЕРАЦИИMAIN TOPIC: HARMONISATION OF PHARMACOPOEIAL STANDARDS: EXPERIENCE OF THE RUSSIAN FEDERATIONПроцедура биовейвер на основе биофармацевтической классификационной системы: регуляторные основания и границы научной интерпретации (обзор)Biowaiver Based on the Biopharmaceutical Classification System: Regulatory Basis and Limits of Scientific Interpretation (Review)https://orcid.org/0009-0000-6421-6052ДахмаН. Д.DahmaN. J.

Дахма Нермин Джозеф, аспирант, кафедра фармацевтической технологии

ул. Победы, д. 85, г. Белгород, 308015

тел.: +7 950 716 67 06

Nermin Joseph Dahma

85 Pobeda St., Belgorod 308015

narmeendahma@gmail.comhttps://orcid.org/0000-0002-8685-1601ЖиляковаЕ. Т.ZhilyakovaE. T.

Жилякова Елена Теодоровна, д-р фарм. наук, профессор

ул. Победы, д. 85, г. Белгород, 308015

Elena T. Zhilyakova, Dr. Sci. (Pharm.), Professor

85 Pobeda St., Belgorod 308015

https://orcid.org/0000-0002-5539-1390ФадееваД. А.FadeevaD. A.

Фадеева Дарья Александровна, канд. фарм. наук, доцент 

ул. Победы, д. 85, г. Белгород, 308015

 

 

Dariya A. Fadeeva, Cand. Sci. (Pharm.), Associate Professor

85 Pobeda St., Belgorod 308015

https://orcid.org/0009-0003-0838-6657ДахмаМ. Д.DahmaM. J.

Дахма Мишель Джозеф

ул. Островитянова, д. 1, Москва, 117997

Michel Joseph Dahma

1 Ostrovityanov St., Moscow 117997

https://orcid.org/0000-0001-9651-2913АльрухаиеР.AlrouhayyahR.

Альрухаие Раним

ул. Миклухо-Маклая, д. 6, Москва, 117198; Дамаск, 30621

Ranim Alrouhayyah

6 Miklukho-Maklay St., Moscow 117198; Damascus 30621

НикитинК. А.NikitinK. A.

Никитин Константин Андреевич 

ул. Победы, д. 85, г. Белгород, 308015

Konstantin A. Nikitin

85 Pobeda St., Belgorod 308015

 

Федеральное государственное автономное образовательное учреждение высшего образования «Белгородский государственный национальный исследовательский университет»РоссияBelgorod State National Research UniversityRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияN.I. Pirogov Russian National Research Medical UniversityRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Российский университет дружбы народов имени Патриса Лумумбы»; Дамасский университетРоссияPeoples’ Friendship University of Russia named after Patrice Lumumba (RUDN); Damascus UniversityRussian Federation202608052026162179189Copyright © Дахма Н.Д., Жилякова Е.Т., Фадеева Д.А., Дахма М.Д., Альрухаие Р., Никитин К.А., 20262026Дахма Н.Д., Жилякова Е.Т., Фадеева Д.А., Дахма М.Д., Альрухаие Р., Никитин К.А.Dahma N.J., Zhilyakova E.T., Fadeeva D.A., Dahma M.J., Alrouhayyah R., Nikitin K.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/845ВВЕДЕНИЕ

ВВЕДЕНИЕ. Процедура биовейвер на основе биофармацевтической классификационной системы (БКС) широко применяется в регуляторной практике при оценке биоэквивалентности воспроизведенных лекарственных препаратов (ВЛП). Применение процедуры биовейвер направлено на сокращение объема исследований in vivo при сохранении требований к качеству, безопасности и эффективности ВЛП. В последние годы в научной литературе активно обсуждаются дополнительные аналитические и модельные инструменты, используемые при оценке биоэквивалентности. Это требует четкого разграничения между регуляторными требованиями и исследовательскими подходами, включая корреляции in vitro / in vivo (IVIVC), физиологически обоснованное фармакокинетическое моделирование (PBPK), а также использование алгоритмов искусственного интеллекта.

ЦЕЛЬ

ЦЕЛЬ. Сравнительный анализ современных нормативных подходов к применению процедуры биовейвер на основе биофармацевтической классификационной системы, а также систематизация действующих требований, применяемых при оценке биоэквивалентности воспроизведенных лекарственных препаратов.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Во всех рассматриваемых регуляторных системах применение процедуры биовейвер нормативно ограничено активными фармацевтическими ингредиентами классов I и III БКС при строгом соблюдении критериев растворимости и сопоставимости профилей растворения. Деление класса II на подклассы IIa и IIb не закреплено ни в одном из официальных регуляторных документов и используется исключительно в научной литературе в исследовательском контексте. Установлено, что такие модели, как IVIVC, PBPK и технологии искусственного интеллекта, рассматриваются регулирующими органами как вспомогательные научные инструменты и не имеют самостоятельного статуса доказательной базы для отказа от исследований in vivo.

ВЫВОДЫ

ВЫВОДЫ. Результаты обзора подтверждают отсутствие принципиальных регуляторных расхождений между подходами к применению процедуры биовейвер. Выявленные в литературе предложения по расширению ее применения относятся к научной дискуссии и не отражают действующую регуляторную практику. Работа формирует методологически корректную основу для интерпретации регуляторных требований и дальнейших исследований в области биофармацевтической оценки ВЛП.

INRODUCTION

INRODUCTION. Biowaiver procedure based on the biopharmaceutics classification system (BCS) is widely used in regulatory practice when assessing the bioequivalence of generic medicinal products (GMPs). The use of the biowaiver is aimed at reducing the rate of in vivo studies while maintaining the requirements for GMP quality, safety, and efficacy. Over the recent years, additional analytical and modeling tools used in bioequivalence assessment have been actively discussed in the scientific literature. This requires a clear distinction between regulatory requirements and research approaches, including in vitro / in vivo correlations (IVIVC), physiologically based pharmacokinetic (PBPK) modeling, and artificial intelligence (AI) algorithms.

AIM

AIM. This study aimed to compare the existing regulatory approaches to the application of the BCS-based biowaiver procedure, with an emphasis on current requirements used to assess GMP bioequivalence.

DISCUSSION

DISCUSSION. In all considered regulatory systems, the use of the biowaiver procedure is limited to active pharmaceutical ingredients (APIs), BCS classes I and III, with strict adherence to solubility criteria and comparability of dissolution profiles. The division of Class II into subclasses IIa and IIb is not stipulated in any official guidelines and is used exclusively in the scientific literature for the research purposes. It has been established that IVIVC, PBPK models, and AI technologies are considered by regulatory authorities as supporting scientific tools and do not have independent status as an evidence base used to renounce the use of in vivo studies.

CONCLUSIONS

CONCLUSIONS. The findings confirm the lack of fundamental regulatory differences between approaches to the biowaiver application. Proposals for expanding biowaiver practice identified in the references relate to scientific controversy without reflecting current regulatory practice. The work forms a methodologically correct basis for the interpretation of regulatory requirements and further research in the area of biopharmaceutical GMPs evaluation.

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