Methodological foundations of pharmaceutical development of cell-based preparations

Alexey V. Lyundup; Люндуп Алексей Валерьевич; Valery V. Beregovykh; Береговых Валерий Васильевич

doi:10.15690/vramn17956

Methodological foundations of pharmaceutical development of cell-based preparations

Authors: Lyundup A.V.¹^,2, Beregovykh V.V.³
Affiliations:
1. RUDN University
2. National Medical Research Center for Endocrinology
3. I.M. Sechenov First Moscow State Medical University (Sechenov University)
Issue: Vol 79, No 6 (2024)
Pages: 551-558
Section: PHARMACOLOGY: CURRENT ISSUES
Published: 15.12.2024
URL: https://vestnikramn.spr-journal.ru/jour/article/view/17956
DOI: https://doi.org/10.15690/vramn17956
ID: 17956

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription or Fee Access

Abstract

Background. The Russian Federation and the Eurasian Economic Union (EAEU) have developed regulatory and legal bases for the circulation of cellular drugs — treatment products based on human somatic cells. Cellular preparations in the Russian Federation are represented by biomedical cellular products with a separate regulatory regulation from medicines, and in the EAEU cellular preparations are classified as a separate class of biological medicines — high-tech medicines. In both regulatory and legal regulations, a pharmaceutical approach has been applied, involving the pharmaceutical development of a cellular drug, its preclinical and clinical studies and subsequent registration for the possibility of release into civil circulation. Cellular drug developers and potential investors are faced with a number of regulated technological and organizational work related to pharmaceutical development that must be performed to bring cellular drugs to market. The requirements, recommendations, concepts and approaches existing in the world are described only for “traditional” medicines and do not describe the necessary types of work in the development of cellular drugs. Aims — to develop methodological foundations for the pharmaceutical development of cellular drugs, as well as to develop a scale of readiness levels of cellular drug technology. Methods. Analysis of the regulatory and legal bases of the Russian Federation and the EAEU, as well as on the basis of the life cycle of cellular drugs, ICH recommendations for the development of pharmaceutical products, the concept of “quality planned during development” QbD. Results. A methodological model for the creation of cellular preparations is proposed, including the stages of theoretical development, laboratory development and industrial development. Based on the methodological model, a scale of readiness levels of cellular drug technology (UGT1–UGT9) was proposed. Conclusions. This article proposes a methodology for the pharmaceutical development of cellular preparations, taking into account a specialized scale of technological readiness levels.

Keywords

cell therapy, cell therapy regulation, regenerative medicines, stem cell, guided tissue regeneration

Full Text

About the authors

Alexey V. Lyundup

RUDN University; National Medical Research Center for Endocrinology

Author for correspondence.
Email: lyundup2020@gmail.com
ORCID iD: 0000-0002-0102-5491
SPIN-code: 4954-3004

MD, PhD

Россия, 6 Miklukho-Maklaya str., 117198, Moscow; Moscow

Valery V. Beregovykh

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: ber2742@gmail.com
ORCID iD: 0000-0002-0210-4570
SPIN-code: 5940-7554

PhD (Technical Sciences), Professor, Academician of the RAS

Россия, Moscow

References

Указ Президента РФ от 7 июля 2011 г. № 899 «Об утверждении приоритетных направлений развития науки, технологий и техники и перечня критических технологий Российской Федерации». [Decree of the President of the Russian Federation dated July 7, 2011 No. 899 “On Approval of priority directions for the development of Science, technology and engineering and the list of critical technologies of the Russian Federation”. (In Russ.)]
Maksimova N, Krasheninnikov M, Zhang Y, et al. Early passage autologous mesenchymal stromal cells accelerate diabetic wound re-epithelialization: A clinical case study. Cytotherapy. 2017;19(12):1548–1550. doi: https://doi.org/10.1016/j.jcyt.2017.08.017
Maksimova NV, Michenko AV, Krasilnikova OA, et al. Mesenchymal stromal cells therapy alone does not lead to the complete restoration of the skin parameters in diabetic foot patients within a 3-year follow-up period. Bioimpacts. 2022;12(1):51–55. doi: https://doi.org/10.34172/bi.2021.22167
Паршин В.Д., Люндуп А.В., Тарабрин Е.А., и др. Отдаленный результат трансплантации трахеи: успех и нерешенные проблемы // Хирургия. Журнал им. Н.И. Пирогова. — 2018. — № 11. — С. 11–19. [Parshin VD, Lyundup AV, Tarabrin EA. Long-term oucomes of tracheal transplantation: success and unsolved problems. Surgery. The magazine named after N.I. Pirogov. 2018;11:11–19. (In Russ.)] doi: https://doi.org/10.17116/hirurgia201811111
de Munter JPJM, Shafarevich I, Liundup A, et al. Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice. CNS Neurosci Ther. 2020;26(5):504–517. doi: https://doi.org/10.1111/cns.13280
Zhang Q, Ping J, Huang Z, et al. CAR-T Cell Therapy in Cancer: Tribulations and Road Ahead. J Immunol Res. 2020;2020:1924379. doi: https://doi.org/10.1155/2020/1924379
Федеральный закон от 23 июня 2016 г. № 180-ФЗ «О биомедицинских клеточных продуктах». [Federal Law of Russian Federation of 23 June 2016 No. 180-FZ “O biomedicinskih kletochnih produktah”. (In Russ.)]
Решение Совета Евразийской экономической комиссии от 3 ноября 2016 г. № 78 (ред. от 23.09.2022) «О Правилах регистрации и экспертизы лекарственных средств для медицинского применения». [Decision of the Council of the Eurasian Economic Commission dated November 3, 2016 No. 78 (ed. dated 09.23.2022) “On the Rules for registration and examination of medicines for medical use”. (In Russ.)]
Приказ Минобрнауки России от 6 февраля 2023 г. № 107 «Об утверждении Порядка определения уровней готовности разрабатываемых или разработанных технологий, а также научных и (или) научно-технических результатов, соответствующих каждому уровню готовности технологий». [Order of the Ministry of Education and Science of the Russian Federation dated February 6, 2023 No. 107 “On Approval of the Procedure for Determining the Readiness levels of developed or Developed Technologies, as well as Scientific and (or) scientific and technical results corresponding to each level of technology availability”. (In Russ.)]
Бркич Г.Э. Методологическое и экспериментальное обоснование реализации концепции «качество, запланированное при разработке» для лекарственных средств: автореф. дис. … д-ра фарм. наук. — М., 2023. — 49 с. [Brkich GE. Metodologicheskoe i eksperimental’noe obosnovanie realizacii koncepcii “kachestvo, zaplanirovannoe pri razrabotke” dlya lekarstvennyh sredstv: avtoref. dis. … d-ra farm. nauk. Moscow; 2023. 49 s. (In Russ.)]