ISO 10993 biological evaluation of novel hemostatic powder – 4SEAL®

다국어 초록 (Multilingual Abstract)

Background: Hemostasis plays a crucial role during every surgery allowing for a bloodless operating field. Fast and effective surgery leads to a reduced risk of postoperative complications. One of the latest methods for achieving homeostasis is using natural polysaccharide-based hemostatic powders. The study aimed to evaluate the biocompatibility according to the ISO 10993 standards of 4SEAL® Hemostatic powder. Methods: Chemical characterization (Headspace GC-MS, GC-MS, and ICP-MS), cytotoxicity, genotoxicity (MLA and AMES), endotoxin contamination, sensitization potential, intracutaneous reactivity, acute and subacute systemic toxicity with implantation, and pyrogenicity were evaluated to investigate the biocompatibility of the 4SEAL® Hemostatic powder. Studies were conducted according to ISO 10993 standards. Results: The biocompatibility requirements according to ISO 10993-1 for 4SEAL® Hemostatic powder were met. Based on the conducted in-vitro studies, 4SEAL® Hemostatic powder shows a non-cytotoxicity and non-mutagenic potential. Also, the results of in vivo studies of 4SEAL® Hemostatic powder shows no signs of toxicity, nonsensitizing, non-irritating, and no pyrogenicity potential. In the chemical characterization of 4Seal® Hemostatic Powder, no compounds were identified above Analytical Evaluation Threshold (AET) and no elements with concentrations higher than element-specific PDE [μg/day] were detected. Conclusions: 4SEAL® Hemostatic powder is a promising new hemostatic agent with a wide range of potential applications and excellent biocompatibility.

참고문헌 (Reference)

1 John R. Hess, "The Coagulopathy of Trauma: A Review of Mechanisms" Ovid Technologies (Wolters Kluwer Health) 65 (65): 748-754, 2008

2 Organisation for Economic Cooperation and Development, "Test No. 490: In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene" OECD

3 Organisation for Economic Cooperation and Development, "Test No. 471: Bacterial Reverse Mutation Test" OECD

4 Rubin R, "Rubin's Pathology:Clinicopathologic Foundations of Medicine" Lippincott Williams & Wilkins 2008

5 Keyvan Karkouti, "Perioperative hemostasis and thrombosis" Springer Science and Business Media LLC 53 (53): 1260-1262, 2006

6 Michelle A Erickson, "Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood–brain barrier" Springer Science and Business Media LLC 9 (9): 2012

7 International Organization for Standardization, "ISO/TR 10993-33:2015(En). Biological Evaluation of Medical Devices — Part 33: Guidance on Tests to Evaluate Genotoxicity — Supplement to ISO 10993-3"

8 International Organization for Standardization, "ISO 10993-6:2016(En). Biological Evaluation of Medical Devices — Part 6: Tests for Local Effects after Implantation"

9 International Organization for Standardization, "ISO 10993-5:2009(En). Biological Evaluation of Medical Devices — Part 5: Tests for in Vitro Cytotoxicity"

10 International Organization for Standardization, "ISO 10993-3:2014(En). Biological Evaluation of Medical Devices — Part 3: Tests for Genotoxicity, Carcinogenicity and Reproductive"

11 International Organization for Standardization, "ISO 10993-1:2018(En). Biological Evaluation of Medical Devices — Part 1: Evaluation and Testing within a Risk Management Process"

12 International Organization for Standardization, "ISO 10993-18:2020(En). Biological Evaluation of Medical Devices — Part 18: Chemical Characterization of Medical Device Materials within a Risk Management Process"

13 International Organization for Standardization, "ISO 10993-12:2021(En). Biological Evaluation of Medical Devices — Part 12: Sample Preparation and Reference Materials"

14 International Organization for Standardization, "ISO 10993-11:2017(En). Biological Evaluation of Medical Devices — Part 11: Tests for Systemic Toxicity"

15 International Organization for Standardization, "ISO 10993-10:2010(En). Biological Evaluation of Medical Devices — Part 10: Tests for Irritation and Skin Sensitization"

16 Food and Drug Administration, U.S, "ICH Q3D(R1):2020. Elemental Impurities; International Council for Harmonisation; Guidance for Industry; Availability" Department of Health & Human Services

17 "Guidance for Industry, Pyrogen and Endotoxins Testing: Questions and Answer"

18 Massimo Franchini, "Factor V Leiden and hemophilia" Elsevier BV 125 (125): 119-123, 2010

19 Mélisande Bernard, "Biocompatibility of polymer-based biomaterials and medical devices – regulations, in vitro screening and risk-management" Royal Society of Chemistry (RSC) 6 (6): 2025-2053, 2018

20 United States Pharmacopeial Convention, "Bacterial Endotoxins Test"

21 Oscar Manouchehrian, "Acute systemic LPS-exposure impairs perivascular CSF distribution in mice" Springer Science and Business Media LLC 18 (18): 2021

22 Bradley A Boucher, "Achieving Hemostasis in the Surgical Field" Wiley 29 (29): 2S-7S, 2009

23 King RC, "A Dictionary of Genetics" Oxford University Press 2007