The Experimental Study of the Quality and Safety of Injectable Implant Medical Devices Based on Hyaluronic Acid in Accordance with the Requirements of the EU Regulation

Authors

DOI:

https://doi.org/10.24959/ophcj.25.339976

Keywords:

quality control, safety, hyaluronic acid, chromatography

Abstract

The aim of the article is to present the results of the experimental study of leachables used as primary packaging for medical devices, namely injectable implants based on hyaluronic acid. For the study, a line of injectable implants with identical qualitative composition and differing quantitative hyaluronic acid content was used. When developing the research conditions, the main characteristics of the implant gel were taken into account, and the conditions for using the appropriate medical device were modeled to obtain the most informative results and confirm the safety of the primary packaging selected. The analysis of extracts was carried out using the following methods: GC/MS, HPLC/UV/MS, ICP/MS, and IC. No substances listed as Chemicals of Potential Concern were detected in the extracts obtained, thereby confirming the safety of using the medical device for the patient under the conditions specified by the manufacturer.

Supporting Agency

  • The author received no specific funding for this work.

Downloads

Download data is not yet available.

References

  1. Bondarets, I.; Sidorenko, L.; Antonenko, O.; Lebed, S.; Georgiyants, V. An approach to the technological process validation of manufacturing medical devices using the example of injectable implants based on hyaluronic acid. Sci. Rise Pharm. Sci. 2024, 6 (52), 111–123. https://doi.org/10.15587/2519-4852.2024.319456.
    |
  2. Li, J.; Sobańtka, A. A systematic analysis of the effect of extraction solvents on the chemical composition of extraction solutions and the analytical implications in extractables and leachables studies. J. Pharm. Biomed. Anal. 2023, 222, 115081. https://doi.org/10.1016/j.jpba.2022.115081.
    | |
  3. Bondarets, I.; Sidorenko, L.; Georgiyants, V.; Mishchenko, V. Regulatory and risk-oriented approach to the design and development of medical devices in accordance with Ukraine regulations. Pharmacia 2022, 69 (2), 493–500. https://doi.org/10.3897/pharmacia.69.e82316.
    |
  4. Regulation (EU) 2017/745 of the European Parliament and of the Council. 2017. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02017R0745-20250110 (accessed June 8, 2025).
  5. Kumaravel, T. S.; Sathya, T. N.; Balaje, R.; Pradeepa, P.; Yogaraj, D.; Murali, M. R.; Navaneethakrishnan, K. R.; Murugan, S.; Jha, A. N. Genotoxicity evaluation of medical devices: A regulatory perspective. Mutation Research/Reviews in Mutation Research 2022, 789, 108407. https://doi.org/10.1016/j.mrrev.2021.108407.
    | |
  6. Bello, W.; Pezzatti, J.; Rudaz, S.; Sadeghipour, F. Study of leachable compounds in hospital pharmacy-compounded prefilled syringes, infusion bags and vials. J. Pharm. Sci. 2024, 113 (11), 3227-3237. https://doi.org/10.1016/j.xphs.2024.08.004.
    | |
  7. Gusain, A.S.; Chandra, S.; Araújo, I.M.; de Lima, J.P.M.; Coutinho, H.D.M. Scientifically Supported Best Practices in Leachable Screening Studies for Pharmaceutical and Parenteral Drug Products. Future Pharmacol. 2025, 5, 18. https://doi.org/10.3390/futurepharmacol5020018.
  8. Satori, C. P.; Christensen, C. D.; Street, S. M.; Giffin, M.; Pohl, C. M.; Christian, W. V. The analytical evaluation threshold for inorganic metal extractables and leachables analysis of medical devices. Regul. Toxicol. Pharm. 2024, 154, 105725. https://doi.org/10.1016/j.yrtph.2024.105725.
    | |
  9. Sündermann, J.; Bitsch, A.; Kellner, R.; Doll, T. Is read-across for chemicals comparable to medical device equivalence and where to use it for conformity assessment? Regul. Toxicol. Pharm. 2024, 149, 105622. https://doi.org/10.1016/j.yrtph.2024.105622.
    | |
  10. Armstrong, B. L.; Senyurt, A. F.; Narayan, V.; Wang, X.; Alquier, L.; Vas, G. Stir bar sorptive extraction combined with GC–MS/MS for determination of low level leachable components from implantable medical devices. J. Pharm. Biomed. Anal. 2013, 74, 162-170. https://doi.org/10.1016/j.jpba.2012.10.019.
    | |
  11. Goud, N. S., Chapter 34 - Biocompatibility Evaluation of Medical Devices. In A Comprehensive Guide to Toxicology in Nonclinical Drug Development (Third Edition), Faqi, A. S., Ed. Academic Press: 2024; pp 957-973. https://doi.org/10.1016/B978-0-323-85704-8.00030-X.
    |
  12. Acosta, M.; Bizzoco, L.; Boiocchi, C.; Gobbi, A., Use of New Formulation in Hyaluronic Acid in Regenerative Medicine. In Regenerative Medicine in Sports and Orthopaedics: A New Approach, Gobbi, A.; Nakamura, N.; Lane, J. G.; Dallo, I., Eds. Springer Nature Switzerland: Cham, 2025; pp 315-324. https://doi.org/10.1007/978-3-031-84693-9_23.
  13. Gao, E. Y.; Tan, B. K. J.; Teo, J. Y. Y.; He, G. S.; Tan, C. J.-W.; Yeo, B. S. Y.; Chua, A. J. K. Hyaluronic Acid for Sinonasal Surgery: A Systematic Review and Meta-Analysis. International Forum of Allergy & Rhinology 2025, 15 (6), 616-625. https://doi.org/10.1002/alr.23537.
    | |
  14. Muhammad, S.; Syed Wasif Ali, S.; Muhammad Abdul, S. Efficacy of Intraarticular Hyaluronic acid and Cortico- Steroid Co-Injection versus Hyaluronic acid in Knee Osteoarthritis. Proceedings S.Z.M.C 2024, 38 (4), 285-289. https://doi.org/10.47489/szmc.v38i4.638.
  15. Torkaman, G.; Rostami-Mehr, E.; Bayat, N.; Mofid, M. Comparing the impact of hyaluronic acid injections and exercise therapy alone and combined on the postural sway and base of support in individuals with knee osteoarthritis: a quasi-experimental study. International Journal of Therapy and Rehabilitation 2025, 32 (4), 1-17. https://doi.org/10.12968/ijtr.2024.0086.
    |
  16. United States Pharmacopeia. General Chapter ⟨1664⟩ Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems; United States Pharmacopeia (USP–NF): Rockville, MD, 2022. https://www.usp.org.
  17. Tanaka, M. L.; Saylor, D. M.; Elder, R. M. Polymer-interface-tissue model to estimate leachable release from medical devices. Mathematical Medicine and Biology: A Journal of the IMA 2024, 41 (4), 382-403. https://doi.org/10.1093/imammb/dqae020.
    | |
  18. Saadati, F.; Bahrulolum, H.; Talebi, M.; Karimi, M.; Bozorgchami, N.; Ghale, R. A.; Zafar, S.; Aghighi, Y.; Asiaei, E.; Tabandeh, F. Advances and principles of hyaluronic acid production, extraction, purification, and its applications: A review. Int. J. Biol. Macromol. 2025, 312, 143839. https://doi.org/10.1016/j.ijbiomac.2025.143839.
    | |
  19. Kostadinova, T.; Trittler, R.; Hoppe, R.; Hug, M. J. 3PC-026 Leachables in syringes containing ethanol, propofol or mRNA vaccine. European Journal of Hospital Pharmacy 2025, 32 (Suppl 1), A29. https://doi.org/10.1136/ejhpharm-2025-eahp.58.
  20. Chandra, G. V.; Bavisetti, L.; Anantam, K. Method Development and Method Validation of Volatile Leachables Amount for Oncology Drug Product Injection by Headspace Gas Chromatography Mass Spectrometry Technique. Res. J. Chem. Environ. 2025, 29 (5), 118–127. https://doi.org/10.25303/295rjce1180127.
    |

Downloads

Published

2025-10-09

How to Cite

(1)
Bondarets, I. R.; Georgiyants, V. A. The Experimental Study of the Quality and Safety of Injectable Implant Medical Devices Based on Hyaluronic Acid in Accordance With the Requirements of the EU Regulation. J. Org. Pharm. Chem. 2025, 23, 28-35.

Issue

Vol. 23 No. 3 (2025)

Section

Original Researches

License

Copyright (c) 2025 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors publishing their works in the Journal of Organic and Pharmaceutical Chemistry agree with the following terms:

1. Authors retain copyright and grant the journal the right of the first publication of the work under Creative Commons Attribution License allowing everyone to distribute and re-use the published material if proper citation of the original publication is given.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book) providing proper citation of the original publication.

3. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on authors’ personal websites) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).