Palavras-chave
Endotoxinas
Técnicas In Vitro
Solução Salina
Como Citar
Resumo
A contaminação por endotoxinas é uma ameaça à segurança dos produtos farmacêuticos, especialmente dos medicamentos parenterais. Qualquer produto farmacêutico estéril e/ou livre de pirogênios requer especificações regulatórias para garantir a segurança de uso para o paciente. Este estudo abrange o estudo de avaliação de desempenho empregando o kit comercial Endozyme II® Go para quantificação de endotoxina, por Fator C recombinante (FCr), em amostras de cloreto de sódio 0,9% para uso parenteral. As amostras foram fortificadas com cinco concentrações distintas de soluções de endotoxina na faixa entre 0,0005 e 10 UE/mL. Cada um dos cinco níveis foi testado pelo menos cinco vezes para avaliação dos critérios de precisão, exatidão, limites de detecção e quantificação, linearidade e robustez. O desvio padrão relativo para os testes de precisão variou de 1,9 a 8,3%. Os valores de recuperação de endotoxina para o parâmetro exatidão estiveram compreendidos entre 61% e 125%. Os resultados demonstraram que o método por FCr permite a quantificação de endotoxinas com exatidão, precisão, especificidade e linearidade para a faixa de 0,005 e 10 UE/mL em amostras de cloreto de sódio 0,9% para uso parenteral.
Referências
Bolden JS, Warburton RE, Phelan R, Murphy M, Smith KR, De Felippis MR, et al. Endotoxin recovery using limulus amebocyte lysate (LAL) assay. Biologicals. 2016;44:434–40. https://doi.org/10.1016/j.biologicals.2016.04.009
Schletter J, Heine H, Ulmer AJ, Rietschel ET. Molecular mechanisms of endotoxin activity. Arch. Microbiol. 1995;164:383–89. https://doi.org/10.1007/BF02529735
DellaGioia N, Hannestad J. A critical review of human endotoxin administration as an experimental paradigm of depression. Neurosci. Biobehav. 2010;34:130–143. https://doi.org/10.1016/j.neubiorev.2009.07.014
Sandle T. Characterizing the Microbiota of a pharmaceutical water system - A metadata study. SOJ Microbiol. Infect. Dis. 2015;3:01–08. https://doi.org/10.15226/sojmid/3/2/00133
United States Pharmacopeia - USP. <1223> Validation of alternative microbiological methods. Rockville: The United States Pharmacopeial Convention, 2023. https://doi.org/10.31003/USPNF_M99943_03_01
Hasiwa N. Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test. ALTEX. 2013;30:169–208. https://doi.org/10.14573/altex.2013.2.169
Greenhough J. Life cycle of an analytical method - A case study on the monocyte activation test. [publisher unknown]. 1–6. Available from: https://wickhammicro.co.uk/Content/Downloads/Wickham-Laboratories-Case-Study-on-the-Monocyte-Activation-Test.pdf
European Medicines Agency - EMA. Guideline on the replacement of rabbit pyrogen testing by an alternative test for plasma derived medicinal products. 2009. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-replacement-rabbit-pyrogen-testing-alternative-test-plasma-derived-medicinal-products_en.pdf
Apparao P, Shashidher B, Ajay KP. Monocyte activation test : A new pharmacoepial quality control test for pyrogens - A Review. J. Adv. Pharm. Sci. 2011;1:122–131
Bolden JS, Claerbout ME, Miner MK, Murphy MA, Smith KR, Warburton RE. Evidence Against a bacterial endotoxin masking effect in biologic drug products by limulus amebocyte lysate detection. PDA J. Pharm. Sci. Technol. 2014;68:472–477. https://doi.org/10.5731/pdajpst.2014.00999
Maloney T, Phelan R, Simmons N. Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood for endotoxin detection. PLoS Biol. 2018;16:1–10. https://doi.org/10.1371/journal.pbio.2006607
Russel MS, Burch RL. The principles of humane experimental technique. Med. J. Aust. 1960;1:500-500. https://doi.org/10.5694/j.1326-5377.1960.tb73127.x
Peterbauer A, Werner ER, Werner-Fermaver G. Further development of a cell culture model for the detection of bacterial pyrogens. ALTEX. 1999;16:3–8
Peterbauer A, Eperon S, Jungi TW, Werner ER, Werner-Felmayer G. Interferon-γ-primed monocytoid cell lines: optimizing their use for in vitro detection of bacterial pyrogens, J. Immunol. Methods. 2000;233:67–76. https://doi.org/10.1016/S0022-1759(99)00189-1
Schindler S, Spreitzer I, Löschner B, Hoffmann S, Hennes K, Halder M, et al. International validation of pyrogen tests based on cryopreserved human primary blood cells, J. Immunol. Methods. 2006;316:42–51. https://doi.org/10.1016/j.jim.2006.07.023
Utescher CLA, Buosi KL, Botosso VF, Quintilio W. Monocyte activation test (MAT) as a possibility of replacement for the rabbit pyrogen test in hyperimmune sera. Brazilian J. Pharm. Sci. 2018;54:3–8. https://doi.org/10.1590/s2175-97902018000217530
Ding JL, Chai C, Pui AWM, Ho B. Expression of full length and deletion homologues of Carcinoscorpius rotundicauda Factor C in Saccharomyces cerevisiae: Immunoreactivity and endotoxin binding, Innate Immun. 1997;4:33–43. https://doi.org/10.1177/096805199700400105
Ding, JL, Ho B. Endotoxin detection - From limulus amebocyte lysate to recombinant factor C. In: Quinn PJ, Xiaoyuan W (Eds.). Endotoxins Struct. Funct. Recognit. Netherlands: Springers; 2010. p. 187–208. https://doi.org/10.1007/978-90-481-9078-2_9
Bolden J, Smith K. Application of recombinant Factor C reagent for the detection of bacterial endotoxins in pharmaceutical products. PDA J. Pharm. Sci. Technol. 2017;71:405–12. https://doi.org/10.5731/pdajpst.2017.007849
Bolden J, Knight M, Stockman S, Omokoko B. Results of a harmonized endotoxin recovery study protocol evaluation by 14 BioPhorum Operations Group (BPOG) member companies. Biologicals. 2017;48:74–81. https://doi.org/10.1016/j.biologicals.2017.05.003
Marius M, Vacher F, Bonnevay T. Comparison of limulus amoebocyte lysate and recombinant factor C assays for endotoxin detection in four human vaccines with complex matrices. PDA J. Pharm. Sci. Technol. 2020;74:394–407. https://doi.org/10.5731/pdajpst.2019.010389
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Validation of analytical procedures: text and methodology Q2(R1). [place unknown]; [publisher unknown]; 2005. Available from: https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf
European Pharmacopoeia. 2.6.32 Test for bacterial endotoxins using recombinant factor C. 10.3 ed. Strasbourg: Council of Europe, 2021.
European Pharmacopoeia. 2.6.14 Bacterial endotoxins. 11.0 ed. Strasbourg: Council of Europe, 2022.
European Pharmacopoeia. Monographs: Water for injections (0169). 11.4 ed. Strasbourg: Council of Europe, 2023.
European Pharmacopoeia. Monographs: Purified Water (0008). 11.4 ed. Strasbourg: Council of Europe, 2023.
BioMérieux. Endozyme II GoTM: rapid detection of endotoxins by recombinant factor. C049458-01. Munchen: BioMérieux; 2018.
Marius M, Vacher F, Bonnevay T. Comparison of bacterial endotoxin testing methods in purified pharmaceutical water matrices. Biologicals. 2020;67:49–55. https://doi.org/10.1016/j.biologicals.2020.07.001
United States Pharmacopeia - USP. <86> Bacterial endotoxins test using recombinant reagents. In: Pharmacopeial Forum 49(6). Rockville: The United States Pharmacopeial Convention, 2023. Available from: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/usp-nf-notices/86-bacterial-endotoxins-tests-using-recombinant-reagents.pdf
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Copyright (c) 2024 Ellen Hilinski, Daniela Dal Molim Ghisleni, Carla Lilian de Agostini Utescher, Wagner Quintilio , Adriana Aparecida Buzzo Almodovar , Adriana Bugno, Terezinha de Jesus Andreoli Pinto