Проблеми класифікації, оцінки безпечності та управління ризиками медичних виробів з біологічно активними речовинами

Автор(и)

  • Олександра Василівна Дмитренко Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського", Україна https://orcid.org/0009-0003-4305-1609
  • Олена Ігорівна Голембіовська Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського", Україна https://orcid.org/0000-0001-5531-5374
  • Вікторія Володимирівна Пашук ТОВ «Юрія-Фарм», Україна https://orcid.org/0000-0002-8225-3997
  • Світлана Миколаївна Згонник ТОВ «Імпрув Медикел», Україна https://orcid.org/0009-0007-9392-6572

DOI:

https://doi.org/10.15587/2519-4852.2025.328031

Ключові слова:

медичні вироби, біологічно активні речовини, оцінка біосумісності, класифікація медичних виробів, регуляторні вимоги, стандарти ISO 10993, Регламент (ЄС) 2017/745, управління ризиками, методи оцінки безпеки, доклінічні дослідження, гармонізація нормативної бази

Анотація

Мета: Дослідження науково-технічних підходів до забезпечення біологічної безпеки та класифікації медичних виробів, що містять біологічно активні речовини, у контексті нових міжнародних стандартів та регуляторних вимог.

Матеріали і методи. Аналіз сучасного нормативного середовища, включаючи Регламент (ЄС) 2017/745, міжнародні стандарти ISO 10993, а також методичні рекомендації Medical Device Coordination Group (MDCG). Досліджено класифікаційні особливості медичних виробів, що містять біологічно активні речовини, з урахуванням їхнього механізму дії. Проведено огляд підходів до оцінки біосумісності та системного аналізу ризиків із застосуванням концепції «ваги доказів» (Weight of Evidence, WoE).

Результати. Розглянуто ключові відмінності між класифікацією медичних виробів відповідно до Директиви 93/42/ЄЕС та Регламенту (ЄС) 2017/745. Визначено особливості оцінки біосумісності медичних виробів, що містять біологічно активні речовини, та проблеми стандартизації їхніх фізико-хімічних показників. Наведено приклади розмежування лікарських засобів та медичних виробів на основі їхнього механізму дії. Проаналізовано впровадження сучасних методів оцінки безпечності медичних виробів та їхнього регуляторного статусу.

Висновки. Нові регуляторні вимоги, зокрема положення Регламенту (ЄС) 2017/745, значно впливають на класифікацію та оцінку біологічної безпеки медичних виробів, що містять біологічно активні речовини. Запропоновано адаптацію методів оцінки біосумісності з урахуванням сучасних тенденцій та підходу "ваги доказів". Визначено необхідність оновлення національного нормативного середовища України для гармонізації з європейськими стандартами та впровадження більш чітких методологічних підходів до розмежування лікарських засобів та медичних виробів

Спонсор дослідження

  • Ministry of Education and Science of Ukraine grant “Development of a gel with wound healing properties for external use” (state registration number 0123U104137)

Біографії авторів

Олександра Василівна Дмитренко, Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського"

Аспірантка

Кафедра трансляційної медичної біоінженерії

Олена Ігорівна Голембіовська, Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського"

Кандидат фармацевтичних наук, доцент

Кафедра трансляційної медичної біоінженерії

Вікторія Володимирівна Пашук, ТОВ «Юрія-Фарм»

Спеціаліст з регуляторних проектів

Світлана Миколаївна Згонник, ТОВ «Імпрув Медикел»

Директор

Посилання

  1. Antich-Isern, P., Caro-Barri, J., Aparicio-Blanco, J. (2021). The combination of medical devices and medicinal products revisited from the new European legal framework. International Journal of Pharmaceutics, 607, 120992. https://doi.org/10.1016/j.ijpharm.2021.120992
  2. Bernard, M., Jubeli, E., Pungente, M. D., Yagoubi, N. (2018). Biocompatibility of polymer-based biomaterials and medical devices – regulations,in vitroscreening and risk-management. Biomaterials Science, 6 (8), 2025–2053. https://doi.org/10.1039/c8bm00518d
  3. European Economic Community. Council Directive 93/42/EEC of 14 of June 1993 concerning medical devices (1993). Official Journal of the European Communities, L 169/1. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:31993L0042&from=EN
  4. European Union. Regulation (EU) No 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/43/EEC (2017). Official Journal of the European Communities, L 117. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0745&from=EN
  5. Guidance on classification of medical devices (2021). Medical Device Coordination Group Document, MDCG 2021-24.
  6. Guidance on borderline between medical devices and medicinal products under Regulation (EU) 2017/745 on medical devices (2024). Medical Device Coordination Group Document, MDCG 2022-5, Rev 1.
  7. Pro zatverdzhennia Tekhnichnoho rehlamentu shchodo medychnykh vyrobiv (2013). Postanova Kabinet ministriv Ukrainy No. 753. 02.10.2013. Available from: https://zakon.rada.gov.ua/laws/show/753-2013-%D0%BF/page
  8. Pro zatverdzhennia metodychnykh rekomendatsii iz zastosuvannia Tekhnichnoho rehlamentu shchodo medychnykh vyrobiv, zatverdzhenoho postanovoiu Kabinetu Ministriv Ukrainy vid 02 zhovtnia 2013 roku No. 753, Tekhnichnoho rehlamentu shchodo medychnykh vyrobiv dlia diahnostyky in vitro, zatverdzhenoho postanovoiu Kabinetu Ministriv Ukrainy vid 02 zhovtnia 2013 roku No. 754, ta Tekhnichnoho rehlamentu shchodo aktyvnykh medychnykh vyrobiv, yaki implantuiut, zatverdzhenoho postanovoiu Kabinetu Ministriv Ukrainy vid 02 zhovtnia 2013 roku No. 755 (2020). Nakazom Ministerstva okhorony zdorovia No. 142. 22.01.2020. Available at: https://zakon.rada.gov.ua/rada/show/v0142282-20
  9. Pro likarski zasoby (2022). Zakon Ukrainy No. 2469-IX. 28.07.2022. Available at: https://zakon.rada.gov.ua/laws/show/2469-20
  10. Zinchenko, V., Chetverikov, S., Akhmad, E., Arzamasov, K., Vladzymyrskyy, A., Andreychenko, A., Morozov, S. (2022). Changes in software as a medical device based on artificial intelligence technologies. International Journal of Computer Assisted Radiology and Surgery, 17 (10), 1969–1977. https://doi.org/10.1007/s11548-022-02669-1
  11. Application of ISO/IEC 17021-1 in the Field of Medical Device Quality Management Systems (ISO 13485) (2023). IAF Mandatory Document.
  12. Malvehy, J., Ginsberg, R., Sampietro‐Colom, L., Ficapal, J., Combalia, M., Svedenhag, P. (2021). New regulation of medical devices in the EU: impact in dermatology. Journal of the European Academy of Dermatology and Venereology, 36 (3), 360–364. https://doi.org/10.1111/jdv.17830
  13. Martelli, N., Eskenazy, D., Déan, C., Pineau, J., Prognon, P., Chatellier, G. et al. (2019). New European Regulation for Medical Devices: What Is Changing? CardioVascular and Interventional Radiology, 42 (9), 1272–1278. https://doi.org/10.1007/s00270-019-02247-0
  14. Stevovic, J. (2019). What MDR class is my eHealth app? The Chino.io Blog. Available at: https://blog.chino.io/what-mdr-class-is-my-software/
  15. BSI Compliance Navigator. Available at: https://compliancenavigator.bsigroup.com/
  16. Melvin, T., Torre, M. (2019). New medical device regulations: the regulator’s view. EFORT Open Reviews, 4 (6), 351–356. https://doi.org/10.1302/2058-5241.4.180061
  17. Ludvigsen, K., Nagaraja, S., Daly, A. (2021). When Is Software a Medical Device? Understanding and Determining the “Intention” and Requirements for Software as a Medical Device in European Union Law. European Journal of Risk Regulation, 13 (1), 78–93. https://doi.org/10.1017/err.2021.45
  18. Liu, A.-A., Wang, Z.-G., Pang, D.-W. (2023). Medical Nanomaterials. Nanomedicine, 51–98. https://doi.org/10.1007/978-981-16-8984-0_5
  19. Chowdhury, N. (2012). Limits to the legal deliberation of science questions: A case study of borderline medical products in Europe. Pharmaceuticals, Policy and Law, 14 (2-4), 157–175. https://doi.org/10.3233/ppl-120351
  20. Tseliou, T. (2015). Balancing Protection of Public Health and Safety with the Free Movement of Goods in the EU Medical Device Sector: The Case of Borderline Productss Classification. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.2585539
  21. Marletta, M. (2020). The new regulation 2017/745: an opportunity for innovation. Pharmadvances, 1 (1). https://doi.org/10.36118/pharmadvances.01.2020.03s
  22. Peter, L., Hajek, L., Maresova, P., Augustynek, M., Penhaker, M. (2020). Medical Devices: Regulation, Risk Classification, and Open Innovation. Journal of Open Innovation: Technology, Market, and Complexity, 6 (2), 42. https://doi.org/10.3390/joitmc6020042
  23. Morán, J., Kilasoniya, A. (2024). Viable Biological Materials or Organisms in Regulation (EU) 2017/745 on Medical Devices. https://doi.org/10.20944/preprints202407.0761.v1
  24. Leone, M. G. (2022). Medical Devices Made of Substances: A New Challenge. Frontiers in Drug Safety and Regulation, 2. https://doi.org/10.3389/fdsfr.2022.952013
  25. Bilia, A. R., Corazziari, E. S., Govoni, S., Mugelli, A., Racchi, M. (2021). Medical Devices Made of Substances: Possible Innovation and Opportunities for Complex Natural Products. Planta Medica, 87 (12/13), 1110–1116. https://doi.org/10.1055/a-1511-8558
  26. Racchi, M., Govoni, S., Lucchelli, A., Capone, L., Giovagnoni, E. (2016). Insights into the definition of terms in European medical device regulation. Expert Review of Medical Devices, 13 (10), 907–917. https://doi.org/10.1080/17434440.2016.1224644
  27. Manellari, S., Leone, M. G., Casiraghi, A., Gennari, C. G. M., Minghetti, P. (2022). Medicinal products, medical devices, or accessories of medical devices: How to qualify gases for spirometry? Frontiers in Drug Safety and Regulation, 2. https://doi.org/10.3389/fdsfr.2022.1089965
  28. Racchi, M., Govoni, S. (2020). The concept of non-pharmacological mechanism of action in medical devices made of substances in practice: what pharmacology can do to promote the scientific implementation of the European medical device regulation. Pharmadvances, 1 (1). https://doi.org/10.36118/pharmadvances.01.2020.02s
  29. MEDDEV 2.1/3 rev. 3 Borderline products, drug-delivery products and medical devices incorporating, as integral part, an ancillary medicinal substance or an ancillary human blood derivative. Available at: https://ec.europa.eu/docsroom/documents/10328/attachments/1/translations
  30. European Community. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Official Journal of the European Communities, L 311, 67. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32001L0083&from=en
  31. Sardi, C., Garetto, S., Capone, L., Galbiati, V., Racchi, M., Govoni, S. et al. (2018). Experimental Paradigm for the Assessment of the Non-pharmacological Mechanism of Action in Medical Device Classification: The Example of Glycerine as Laxative. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.01410
  32. Santos, I. C., Gazelle, G. S., Rocha, L. A., Tavares, J. M. R. (2012). Medical device specificities: opportunities for a dedicated product development methodology. Expert Review of Medical Devices, 9 (3), 299–311. https://doi.org/10.1586/erd.12.3
  33. Fimognari, C., Barrajón-Catalán, E., Luceri, C., Turrini, E., Raschi, E., Bigagli, E. (2022). New regulation on medical devices made of substances: Opportunities and challenges for pharmacological and toxicological research. Frontiers in Drug Safety and Regulation, 2. https://doi.org/10.3389/fdsfr.2022.1001614
  34. Santus, P., Signorello, J. C., Danzo, F., Lazzaroni, G., Saad, M., Radovanovic, D. (2024). Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective. Journal of Clinical Medicine, 13 (14), 4127. https://doi.org/10.3390/jcm13144127
  35. Pedre, B., Barayeu, U., Ezeriņa, D., Dick, T. P. (2021). The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacology & Therapeutics, 228, 107916. https://doi.org/10.1016/j.pharmthera.2021.107916
  36. Public data from Article 57 database. European Medicines Agency (EMA). Available at: https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/data-medicines-iso-idmp-standards-post-authorisation/public-data-article-57-database
  37. Rinofast Flu. PJPHARMA. Available at: https://www.pjpharma.it/en/products/rinofast-flu
  38. Viscoflu linea. pharma-line.it Available at: https://pharma-line.it/en/prodotto-exp/viscoflu-linea/
  39. Devices/Systems/Procedure packs. EUDAMED. Available at: https://ec.europa.eu/tools/eudamed/#/screen/search-device?tradeName=Vagi-C%C2%AE&deviceStatusCode=refdata.device-model-status.on-the-market&submitted=true
  40. Meloni, M., De Servi, B., Carriero, F., Simon O’Brien, E., Houamel, D., Deruelle, P., Castagné, V. (2024). Demonstrating the principal mechanism of action of medical devices intended for vaginal use on reconstructed human vaginal epithelium: the case of two hyaluronic acid-containing devices. Frontiers in Drug Safety and Regulation, 4. https://doi.org/10.3389/fdsfr.2024.1445519
  41. Huang, T., Zhang, Y., Zhao, L., Ren, Y., Wang, K., Zhang, N. et al. (2024). Sodium hyaluronate hydrogel for wound healing and human health monitoring based on deep eutectic solvent. International Journal of Biological Macromolecules, 257, 128801. https://doi.org/10.1016/j.ijbiomac.2023.128801
  42. Yasin, A., Ren, Y., Li, J., Sheng, Y., Cao, C., Zhang, K. (2022). Advances in Hyaluronic Acid for Biomedical Applications. Frontiers in Bioengineering and Biotechnology, 10. https://doi.org/10.3389/fbioe.2022.910290
  43. Vasvani, S., Kulkarni, P., Rawtani, D. (2020). Hyaluronic acid: A review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies. International Journal of Biological Macromolecules, 151, 1012–1029. https://doi.org/10.1016/j.ijbiomac.2019.11.066
  44. Juncan, A. M., Moisă, D. G., Santini, A., Morgovan, C., Rus, L.-L., Vonica-Țincu, A. L., Loghin, F. (2021). Advantages of Hyaluronic Acid and Its Combination with Other Bioactive Ingredients in Cosmeceuticals. Molecules, 26 (15), 4429. https://doi.org/10.3390/molecules26154429
  45. Tamer, T. M. (2013). Hyaluronan and synovial joint: function, distribution and healing. Interdisciplinary Toxicology, 6 (3), 111–125. https://doi.org/10.2478/intox-2013-0019
  46. Vassallo, V., Di Meo, C., Toro, G., Alfano, A., Iolascon, G., Schiraldi, C. (2023). Hyaluronic Acid-Based Injective Medical Devices: In Vitro Characterization of Novel Formulations Containing Biofermentative Unsulfated Chondroitin or Extractive Sulfated One with Cyclodextrins. Pharmaceuticals, 16 (10), 1429. https://doi.org/10.3390/ph16101429
  47. Gupta, R. C., Lall, R., Srivastava, A., Sinha, A. (2019). Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory. Frontiers in Veterinary Science, 6. https://doi.org/10.3389/fvets.2019.00192
  48. Rah, M. J. (2011). A review of hyaluronan and its ophthalmic applications. Optometry – Journal of the American Optometric Association, 82 (1), 38–43. https://doi.org/10.1016/j.optm.2010.08.003
  49. Marchesi, N., Fahmideh, F., Barbieri, A., Racchi, M., Pascale, A., Govoni, S. (2022). Pharmacological Versus Non-Pharmacological and Ancillary Mechanisms in Eye Drops Used in the Treatment of Glaucoma. Frontiers in Drug Safety and Regulation, 2. https://doi.org/10.3389/fdsfr.2022.933471
  50. Jasielski, P., Piędel, F., Piwek, M., Rocka, A., Petit, V., Rejdak, K. (2020). Application of Citicoline in Neurological Disorders: A Systematic Review. Nutrients, 12(10), 3113. https://doi.org/10.3390/nu12103113
  51. Świątkiewicz, M., Grieb, P. (2022). Citicoline for Supporting Memory in Aging Humans. Aging and Disease, 14 (4), 1184–1195. https://doi.org/10.14336/ad.2022.0913
  52. Grieb, P. (2015). Citicoline: A Food That May Improve Memory. Medical Science Review, 2, 67–72. https://doi.org/10.12659/msrev.894711
  53. Gandolfi, S., Marchini, G., Caporossi, A., Scuderi, G., Tomasso, L., Brunoro, A. (2020). Cytidine 5′-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma. Nutrients, 12 (3), 793. https://doi.org/10.3390/nu12030793
  54. Faiq, M. A., Wollstein, G., Schuman, J. S., Chan, K. C. (2019). Cholinergic nervous system and glaucoma: From basic science to clinical applications. Progress in Retinal and Eye Research, 72, 100767. https://doi.org/10.1016/j.preteyeres.2019.06.003
  55. Carnevale, C., Manni, G., Roberti, G., Micera, A., Bruno, L., Cacciamani, A. et al. (2019). Human vitreous concentrations of citicoline following topical application of citicoline 2% ophthalmic solution. PLOS ONE, 14 (11), e0224982. https://doi.org/10.1371/journal.pone.0224982
  56. OMK1 Citicoline Eye Drop. Omikron. Available at: https://www.citicolineomk1.com/
  57. Gilbert, B., Alves, L. (2003). Synergy in Plant Medicines. Current Medicinal Chemistry, 10 (1), 13–20. https://doi.org/10.2174/0929867033368583
  58. Thomford, N. E., Senthebane, D. A., Rowe, A., Munro, D., Seele, P., Maroyi, A., Dzobo, K. (2018). Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences, 19 (6), 1578. https://doi.org/10.3390/ijms19061578
  59. Wanjek, C. (2022). Systems Biology as defined by NIH. NIH Intramural Research Program. Available at: https://irp.nih.gov/catalyst/19/6/systems-biology-as-defined-by-nih
  60. Giovagnoni, E. (2022). Substance-based medical devices made of natural substances: An opportunity for therapeutic innovation. Frontiers in Drug Safety and Regulation, 2. https://doi.org/10.3389/fdsfr.2022.998114
  61. Guarino, G., Della Corte, T., Strollo, F., Gentile, S. (2021). Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15 (3), 901–907. https://doi.org/10.1016/j.dsx.2021.03.032
  62. Mercati, V. (2005). EP1679009A1. Pharmaceutical and dietetic compositions based on vegetable fibres. Available at: https://patents.google.com/patent/EP1679009A1/en
  63. Greco, C. M., Garetto, S., Montellier, E., Liu, Y., Chen, S., Baldi, P. et al. (2020). A non-pharmacological therapeutic approach in the gut triggers distal metabolic rewiring capable of ameliorating diet-induced dysfunctions encompassed by metabolic syndrome. Scientific Reports, 10 (1). https://doi.org/10.1038/s41598-020-69469-y
  64. Stagi, S., Lapi, E., Seminara, S., Pelosi, P., Del Greco, P., Capirchio, L. et al. (2015). Policaptil Gel Retard® significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM. Italian Journal of Pediatrics, 41 (1). https://doi.org/10.1186/s13052-015-0109-7
  65. Guarino, G., Strollo, F., Della-Corte, T., Satta, E., Romano, C., Alfarone, C. et al. (2022). Comparison between Policaptil Gel Retard and Metformin by Testing of Temporal Changes in Patients with Metabolic Syndrome and Type 2 Diabetes. Diabetology, 3 (2), 315–327. https://doi.org/10.3390/diabetology3020022
  66. Marletta, M. (2024). Regulation 2017/745 on medical devices, two major innovations: 1) the physiological action of devices consisting of natural materials such as vegetal matrices; 2) the chemical-physical-mechanical action of devices made of “substances”, which as such are artificial derivatives. Frontiers in Drug Safety and Regulation, 4. https://doi.org/10.3389/fdsfr.2024.1389406
  67. Lee, S. (2015). Systems Biology – A Pivotal Research Methodology for Understanding the Mechanisms of Traditional Medicine. Journal of Pharmacopuncture, 18 (3), 11–18. https://doi.org/10.3831/kpi.2015.18.020
  68. Rai, S., Raj, U., Varadwaj, P. K. (2018). Systems Biology: A Powerful Tool for Drug Development. Current Topics in Medicinal Chemistry, 18 (20), 1745–1754. https://doi.org/10.2174/1568026618666181025113226
  69. Chaachouay, N., Zidane, L. (2024). Plant-Derived Natural Products: A Source for Drug Discovery and Development. Drugs and Drug Candidates, 3 (1), 184–207. https://doi.org/10.3390/ddc3010011
  70. Aronson, J. K., Heneghan, C., Ferner, R. E. (2019). Medical Devices: Definition, Classification, and Regulatory Implications. Drug Safety, 43 (2), 83–93. https://doi.org/10.1007/s40264-019-00878-3
  71. Gorchakova, N., Harnyk, T., Khudetskyy, I., Dmytrenko, A., Bespalova, O., Biloshytska, O. (2024). Analysis of current data on the safety and efficacy of the phloroglucinol and simeticone combination (literature review). Fitoterapia, 2, 5–20. https://doi.org/10.32782/2522-9680-2024-2-5
  72. De Jong, W. H., Carraway, J. W., Geertsma, R. E. (2012). In vivo and in vitro testing for the biological safety evaluation of biomaterials and medical devices. Biocompatibility and Performance of Medical Devices, 120–158. https://doi.org/10.1533/9780857096456.2.120
  73. Kanďárová, H., Pôbiš, P. (2024). The “Big Three” in biocompatibility testing of medical devices: implementation of alternatives to animal experimentation –are we there yet? Frontiers in Toxicology, 5. https://doi.org/10.3389/ftox.2023.1337468
  74. ISO 10993-1:2018 (2018). Biological evaluation of medical devices. Part 1: evaluation and testing within a risk management process. Edition 5. Geneva: International Organization for Standardization.
  75. Sündermann, J., Bitsch, A., Kellner, R., Doll, T. (2024). Is read-across for chemicals comparable to medical device equivalence and where to use it for conformity assessment? Regulatory Toxicology and Pharmacology, 149, 105622. https://doi.org/10.1016/j.yrtph.2024.105622
  76. Larionov, V., Golovenko, M., Valivodz, I., Reder, A. (2025). Inhibition of Cytochrome P450 Activities by Propoxazepam: Safety Assessment in Context for Potential Drug Interactions. Innovative Biosystems and Bioengineering, 9 (2), 4–11. https://doi.org/10.20535/ibb.2025.9.2.309378
  77. Skavinska, O. О., Rossokha, Z. I., Podolska, S. V., Ievseienkova, O. G., Buriak, O. A., Olkhovych, V. P., Gorovenko, N. G. (2024). The role of pharmacogenomic studies in increasing the effectiveness and safety of clinical application of statins. Clinical and Preventive Medicine, 5, 109–123. https://doi.org/10.31612/2616-4868.5.2024.14
  78. Halkin, O. Iu., Savchenko, A. A., Nikitina, K. I., Duhan, O. M. (1999). Isolation and characterization of new monoclonal antibodies against human IgE. Ukrainian Biochemical Journal, 85 (5), 81–87. Available at: https://pubmed.ncbi.nlm.nih.gov/24479325/
  79. Shevchuk, K., Baranovska, A., Chernetskyi, A., Besarab, A. (2025). Biosafety Aspects of Hybridoma Technology: Nature of Risks and Approaches to their Management. Innovative Biosystems and Bioengineering, 9 (2), 29–41. https://doi.org/10.20535/ibb.2025.9.2.320712
  80. Street, S. M., Christian, W. V. (2024). Taring the scales: Weight-of-evidence framework for biocompatibility evaluations. Regulatory Toxicology and Pharmacology, 149, 105590. https://doi.org/10.1016/j.yrtph.2024.105590
  81. ISO 10993-5:2009 (2009). Biological evaluation of medical devices. Part 5: tests for in vitro cytotoxicity. Edition 3. Geneva: International Organization for Standardization.
  82. ISO 10993-10:2021 (2021). Biological evaluation of medical devices. Part 10: tests for skin sensitization. Edition 4. Geneva: International Organization for Standardization.
  83. ISO 10993-4:2017 (2017). Biological evaluation of medical devices. Part 4: selection of tests for interactions with blood. Edition 3. Geneva: International Organization for Standardization.
  84. ISO 10993-11:2017 (2017). Biological evaluation of medical devices. Part 11: tests for systemic toxicity. Edition 3. Geneva: International Organization for Standardization.
  85. Fomina, N. S., Kovalchuk, V. P., Vovk, I. M., Fomin, O. O., Kovalenko, I. M. (2024). Antimicrobial activity assessment of food preservatives containing organic carboxylic acids. Clinical and Preventive Medicine, 5, 80–86. https://doi.org/10.31612/2616-4868.5.2024.10
  86. Key learnings from ISO 10993-23:2021: Biological evaluation of medical devices – Tests for irritation. Congenius. 2022. Available at: https://congenius.ch/biological-evaluation-medical-devices-tests-for-irritation/
  87. Gruber, S., Nickel, A. (2023). Toxic or not toxic? The specifications of the standard ISO 10993-5 are not explicit enough to yield comparable results in the cytotoxicity assessment of an identical medical device. Frontiers in Medical Technology, 5. https://doi.org/10.3389/fmedt.2023.1195529
  88. Stordeur, S., Vinck, I., Neyt, M., Van Brabandt, H., Hulstaert, F. (2013). Mise sur le marché européen des dispositifs médicaux innovants à haut risque : l’efficacité clinique et la sécurité sont-elles garanties ? Revue d’Épidémiologie et de Santé Publique, 61 (2), 105–110. https://doi.org/10.1016/j.respe.2012.08.004
  89. Räägel, H., Turley, A., Fish, T., Franson, J., Rollins, T., Campbell, S., Jorgensen, M. R. (2021). Medical Device Industry Approaches for Addressing Sources of Failing Cytotoxicity Scores. Biomedical Instrumentation & Technology, 55 (2), 69–84. https://doi.org/10.2345/0899-8205-55.2.69
  90. Goller, S., Turner, N. J. (2020). The Antimicrobial Effectiveness and Cytotoxicity of the Antibiotic-Loaded Chitosan: ECM Scaffolds. Applied Sciences, 10 (10), 3446. https://doi.org/10.3390/app10103446
  91. Suter, G., Cormier, S., Barron, M. (2017). A weight of evidence framework for environmental assessments: Inferring qualities. Integrated Environmental Assessment and Management, 13 (6), 1038–1044. https://doi.org/10.1002/ieam.1954
  92. Suter, G., Cormier, S., Barron, M. (2017). A weight of evidence framework for environmental assessments: Inferring quantities. Integrated Environmental Assessment and Management, 13 (6), 1045–1051. https://doi.org/10.1002/ieam.1953
  93. Pistollato, F., Madia, F., Corvi, R., Munn, S., Grignard, E., Paini, A. et al. (2021). Current EU regulatory requirements for the assessment of chemicals and cosmetic products: challenges and opportunities for introducing new approach methodologies. Archives of Toxicology, 95 (6), 1867–1897. https://doi.org/10.1007/s00204-021-03034-y
  94. Rocca, M., Morford, L. L., Blanset, D. L., Halpern, W. G., Cavagnaro, J., Bowman, C. J. (2018). Applying a weight of evidence approach to the evaluation of developmental toxicity of biopharmaceuticals. Regulatory Toxicology and Pharmacology, 98, 69–79. https://doi.org/10.1016/j.yrtph.2018.07.006
  95. Dmytrenko, O., Lutsenko, T., Dmytrenko, A., Bespalova, O. (2024). Assessment of Efficiency and Safety of Phytocomposition with Prostate-Protective Properties in the form of Rectal Suppositories. Natural and Engineering Sciences, 9 (2), 407–425. https://doi.org/10.28978/nesciences.1465276
  96. Dronko, L. M., Lutsenko, T. M., Korotkevych, N. V., Vovk, I. O., Zhukova, D. A., Romaniuk, S. I. et al. (2024). Heparin-binding EGF-like growth factor: mechanisms of biological activity and potential therapeutic applications. The Ukrainian Biochemical Journal, 96 (5), 5–20. https://doi.org/10.15407/ubj96.05.005
  97. Strickland, J., Haugabrooks, E., Allen, D. G., Balottin, L. B., Hirabayashi, Y., Kleinstreuer, N. C. et al. (2023). International regulatory uses of acute systemic toxicity data and integration of new approach methodologies. Critical Reviews in Toxicology, 53 (7), 385–411. https://doi.org/10.1080/10408444.2023.2240852
  98. Tandy, J., Hanhquynh Le, K., Michael Deane, G., Joseph Burns, S. (2022). Cleanability of Metal Surface Finishes Found in Medical Devices and the Environment of Care. Biomedical Instrumentation & Technology, 56 (2), 29–36. https://doi.org/10.2345/1943-5967-56.2.29
  99. Sussman, E. M., Oktem, B., Isayeva, I. S., Liu, J., Wickramasekara, S., Chandrasekar, V. et al. (2022). Chemical Characterization and Non-targeted Analysis of Medical Device Extracts: A Review of Current Approaches, Gaps, and Emerging Practices. ACS Biomaterials Science & Engineering, 8 (3), 939–963. https://doi.org/10.1021/acsbiomaterials.1c01119
  100. ISO 10993-17:2023 (2023). Biological evaluation of medical devices. Part 17: toxicological risk assessment of medical device constituents. Edition 2. Geneva: International Organization for Standardization.
  101. Toxicological Risk Assessment of Medical Devices. Available at: https://www.tuvsud.com/en/industries/healthcare-and-medical-devices/medical-devices-and-ivd/medical-device-testing/toxicological-risk-assessment-of-medical-devices
  102. ISO 10993-18:2020 (2020). Biological evaluation of medical devices. Part 18: chemical characterization of medical device materials within a risk management process. Edition 2. Geneva: International Organization for Standardization.
  103. ISO/TS 10993-19:2020 (2020). Biological evaluation of medical devices. Part 19: physico-chemical, morphological and topographical characterization of materials. Edition 2. Geneva: International Organization for Standardization.
  104. Liu, X., Rodeheaver, D. P., White, J. C., Wright, A. M., Walker, L. M., Zhang, F., Shannon, S. (2018). A comparison of in vitro cytotoxicity assays in medical device regulatory studies. Regulatory Toxicology and Pharmacology, 97, 24–32. https://doi.org/10.1016/j.yrtph.2018.06.003
  105. McDermott, O., Kearney, B. (2023). The value of using real-world evidence as a source of clinical evidence in the European medical device regulations: a mixed methods study. Expert Review of Medical Devices, 21 (1-2), 149–163. https://doi.org/10.1080/17434440.2023.2291454
  106. Pane, J., Francisca, R. D. C., Verhamme, K. M. C., Orozco, M., Viroux, H., Rebollo, I., Sturkenboom, M. C. J. M. (2019). EU postmarket surveillance plans for medical devices. Pharmacoepidemiology and Drug Safety, 28 (9), 1155–1165. https://doi.org/10.1002/pds.4859
  107. Establishing quality specifications for medicines, vaccines and in vitro diagnostics: week of quality 2023 training kit (2024). World Health Organization. Available at: https://www.who.int/publications/i/item/978924009599
  108. Albert, D. E. (2012). Material and chemical characterization for the biological evaluation of medical device biocompatibility. Biocompatibility and Performance of Medical Devices. Elsevier eBooks, 65–94. https://doi.org/10.1533/9780857096456.2.63
  109. Kramer D. B., Tan, Y. T., Sato, C., Kesselheim, A. S. (2014). Ensuring medical device effectiveness and safety: a cross--national comparison of approaches to regulation. Food and Drug Law Journal, 69 (1), 1–23. Available at: https://pubmed.ncbi.nlm.nih.gov/24772683
  110. Galkin, O. Yu., Lutsenko, T. M., Gorshunov, Yu. V., Motronenko, V. V. (2017). Development of the method for microbiological purity testing of recombinant human interleukin-7-based product. The Ukrainian Biochemical Journal, 89(3), 52–59. https://doi.org/10.15407/ubj89.03.052
  111. Umamaheswari, D., Muthuraja, R., Kumar, M., Venkateswarlu, B. S. (2021). Standardization of Herbal Drugs – A Overview. International Journal of Pharmaceutical Sciences Review and Research, 68 (1). https://doi.org/10.47583/ijpsrr.2021.v68i01.033
  112. Noviana, E., Indrayanto, G., Rohman, A. (2022). Advances in Fingerprint Analysis for Standardization and Quality Control of Herbal Medicines. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.853023
  113. Atanasov, A. G., Waltenberger, B., Pferschy-Wenzig, E.-M., Linder, T., Wawrosch, C., Uhrin, P. et al. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33 (8), 1582–1614. https://doi.org/10.1016/j.biotechadv.2015.08.001
  114. Bagade, S., Patil, D. D., Shirkhedkar, A. (2022). Standardization of herbal bioactives. Herbal Bioactive-Based Drug Delivery Systems. Elsevier eBooks, 393–407. https://doi.org/10.1016/b978-0-12-824385-5.00005-4
  115. Wang, H., Chen, Y., Wang, L., Liu, Q., Yang, S., Wang, C. (2023). Advancing herbal medicine: enhancing product quality and safety through robust quality control practices. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1265178
  116. Barba-Ostria, C., Carrera-Pacheco, S. E., Gonzalez-Pastor, R., Heredia-Moya, J., Mayorga-Ramos, A., Rodríguez-Pólit, C. et al. (2022). Evaluation of Biological Activity of Natural Compounds: Current Trends and Methods. Molecules, 27 (14), 4490. https://doi.org/10.3390/molecules27144490
  117. Govindaraghavan, S., Sucher, N. J. (2015). Quality assessment of medicinal herbs and their extracts: Criteria and prerequisites for consistent safety and efficacy of herbal medicines. Epilepsy & Behavior, 52, 363–371. https://doi.org/10.1016/j.yebeh.2015.03.004
  118. Li, Y., Kong, D., Fu, Y., Sussman, M. R., Wu, H. (2020). The effect of developmental and environmental factors on secondary metabolites in medicinal plants. Plant Physiology and Biochemistry, 148, 80–89. https://doi.org/10.1016/j.plaphy.2020.01.006
  119. Ponphaiboon, J., Krongrawa, W., Aung, W. W., Chinatangkul, N., Limmatvapirat, S., Limmatvapirat, C. (2023). Advances in Natural Product Extraction Techniques, Electrospun Fiber Fabrication, and the Integration of Experimental Design: A Comprehensive Review. Molecules, 28 (13), 5163. https://doi.org/10.3390/molecules28135163
  120. Khudetskyy, I., Antonova-Rafi, J. (2023). Human influence and changes in nature on biological security (overview of the problem). Fitoterapia, 2, 26–34. https://doi.org/10.32782/2522-9680-2023-2-37
  121. Klein-Junior, L. C., de Souza, M. R., Viaene, J., Bresolin, T. M. B., de Gasper, A. L., Henriques, A. T., Heyden, Y. V. (2021). Quality Control of Herbal Medicines: From Traditional Techniques to State-of-the-art Approaches. Planta Medica, 87 (12/13), 964–988. https://doi.org/10.1055/a-1529-8339
  122. Guidance on standardisation for medical devices (2024). MDCG 2021-5, Rev. 1. Medical Device Coordination Group.
  123. Golembiovska, O., Dmytrenko, O., Galkin, A. (2024). Design and Development of Novel Herbal Suppository Formulation for Prostatitis Treatment. Innovative Biosystems and Bioengineering, 8 (4), 23–38. https://doi.org/10.20535/ibb.2024.8.4.317124
  124. Görög, S. (2018). Critical review of reports on impurity and degradation product profiling in the last decade. TrAC Trends in Analytical Chemistry, 101, 2–16. https://doi.org/10.1016/j.trac.2017.09.012
  125. Singh, G., Lu, D., Liu, C., Hower, D. (2021). Analytical challenges and recent advances in the identification and quantitation of extractables and leachables in pharmaceutical and medical products. TrAC Trends in Analytical Chemistry, 141, 116286. https://doi.org/10.1016/j.trac.2021.116286
  126. Ram, M., Abdin, M. Z., Khan, M. A., Jha, P. (2010). HPTLC Fingerprint Analysis: A Quality Control for Authentication of Herbal Phytochemicals. High-Performance Thin-Layer Chromatography (HPTLC). Springer eBooks, 105–116. https://doi.org/10.1007/978-3-642-14025-9_7
  127. Sharma, A., Chauhan, R., Kumar, R., Mankotia, P., Verma, R., Sharma, V. (2021). A rapid and non-destructive ATR-FTIR spectroscopy method supported by chemometrics for discriminating between facial creams and the classification into herbal and non-herbal brands. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 258, 119803. https://doi.org/10.1016/j.saa.2021.119803
  128. Muyumba, N. W., Mutombo, S. C., Sheridan, H., Nachtergael, A., Duez, P. (2021). Quality control of herbal drugs and preparations: The methods of analysis, their relevance and applications. Talanta Open, 4, 100070. https://doi.org/10.1016/j.talo.2021.100070
  129. Indrayanto, G. (2022). The importance of method validation in herbal drug research. Journal of Pharmaceutical and Biomedical Analysis, 214, 114735. https://doi.org/10.1016/j.jpba.2022.114735
  130. Hasija, M., Sheung, A., Rahman, N., Ausar, S. F. (2016). Stressed Stability Techniques for Adjuvant Formulations. Vaccine Adjuvants, 227–238. https://doi.org/10.1007/978-1-4939-6445-1_16
Проблеми класифікації, оцінки безпечності та управління ризиками медичних виробів з біологічно активними речовинами

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2025-04-30

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Дмитренко, О. В., Голембіовська, О. І., Пашук, В. В., & Згонник, С. М. (2025). Проблеми класифікації, оцінки безпечності та управління ризиками медичних виробів з біологічно активними речовинами. ScienceRise: Pharmaceutical Science, (2 (54), 86–104. https://doi.org/10.15587/2519-4852.2025.328031

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