Abstract
Background: Pyrogens are fever-inducing substances and pyrogen detection is mandatory in parenteral pharmaceuticals. Succinylated Gelatin Injection (SGI) is a biopharmaceutical product, containing multi-component, and it is administered parenterally.
Objective: The study aimed to assess pyrogen in SGI and to evaluate the feasibility of the Monocyte Activation Test (MAT) for pyrogen detection in a multi-component pharmaceutical product.
Method: In the present study, the Bacterial Endotoxin Test (BET) and the Monocyte Activation Test (MAT) were employed to assess pyrogen in SGI. The MAT method was developed on the basis of the HL-60/IL-6 assay. HL-60 cells were incubated with lipopolysaccharide (LPS) standards and sample solutions. The endotoxin produced by the incubation, interleukin-6 (IL-6), was measured by ELISA. The MAT method was validated and main parameters were investigated. Finally, the pyrogenicity of SGIs from two different enterprises was determined by the developed MAT method.
Results: The BET failed in the test for interfering factors and the MAT was proved suitable for the pyrogen detection of SGI. All the products examined showed negative results in the pyrogen detection test.
Conclusion: The MAT method is feasible in pyrogen detection of SGI. It can be applied in pyrogen detection for quality and safety control of multi-component biological products.
Keywords: Pyrogen, endotoxin, bacterial endotoxin test, monocyte activation test, ELISA, succinylated gelatin injection.
Graphical Abstract
[1]
Nordgren, I.K. Leukoreduction system chambers provide a valuable source of functional monocytes for the monocyte activation test by comparison with internationally validated methods. J. Immunol. Methods, 2016, 428, 42-49.
[http://dx.doi.org/10.1016/j.jim.2015.12.001] [PMID: 26678159]
[http://dx.doi.org/10.1016/j.jim.2015.12.001] [PMID: 26678159]
[2]
He, Q.; Gao, H.; Xu, L.M.; Lu, Y.; Wang, C.; Rui, J.; Fan, H.; Wang, X.Y.; Wang, J.Z. Analysis of IL-6 and IL-1β release in cryopreserved pooled human whole blood stimulated with endotoxin. Innate Immun., 2018, 24(5), 316-322.
[http://dx.doi.org/10.1177/1753425918777596] [PMID: 29793382]
[http://dx.doi.org/10.1177/1753425918777596] [PMID: 29793382]
[3]
Stang, K.; Fennrich, S.; Krajewski, S.; Stoppelkamp, S.; Burgener, I.A.; Wendel, H.P.; Post, M. Highly sensitive pyrogen detection on medical devices by the monocyte activation test. J. Mater. Sci. Mater. Med., 2014, 25(4), 1065-1075.
[http://dx.doi.org/10.1007/s10856-013-5136-6] [PMID: 24414113]
[http://dx.doi.org/10.1007/s10856-013-5136-6] [PMID: 24414113]
[4]
Li, K.; Xu, H.; Jiang, W.; Li, J.; Liu, W.; Wang, T.; Fang, M. Development and characterization of stable reporter cells for fast and sensitive detection of pyrogen. Anal. Biochem., 2018, 557, 69-76.
[http://dx.doi.org/10.1016/j.ab.2018.07.016] [PMID: 30030993]
[http://dx.doi.org/10.1016/j.ab.2018.07.016] [PMID: 30030993]
[5]
Pardo-Ruiz, Z.; Menéndez-Sardiñas, D.E.; Pacios-Michelena, A.; Gabilondo-Ramírez, T.; Montero-Alejo, V.; Perdomo-Morales, R. Soluble β-(1,3)-glucans enhance LPS-induced response in the monocyte activation test, but inhibit LPS-mediated febrile response in rabbits: Implications for pyrogenicity tests. Eur. J. Pharm. Sci., 2016, 81, 18-26.
[http://dx.doi.org/10.1016/j.ejps.2015.09.018] [PMID: 26428698]
[http://dx.doi.org/10.1016/j.ejps.2015.09.018] [PMID: 26428698]
[6]
Chinese Pharmacopoeia Commission. Pharmacopoeia of People’s
Republic of China; China Medical Science and Technology Publishing
House: Beijing, 2015, Vol. IV, pp. 153-157 (in Chinese).
[7]
Su, W.; Ding, X. Methods of endotoxin detection. J. Lab. Autom., 2015, 20(4), 354-364.
[http://dx.doi.org/10.1177/2211068215572136] [PMID: 25720597]
[http://dx.doi.org/10.1177/2211068215572136] [PMID: 25720597]
[8]
Gimenes, I.; Caldeira, C.; Presgrave, O.A.F.; de Moura, W.C.; Villas Boas, M.H. Assessment of pyrogenic response of lipoteichoic acid by the monocyte activation test and the rabbit pyrogen test. Regul. Toxicol. Pharmacol., 2015, 73(1), 356-360.
[http://dx.doi.org/10.1016/j.yrtph.2015.07.025] [PMID: 26232706]
[http://dx.doi.org/10.1016/j.yrtph.2015.07.025] [PMID: 26232706]
[9]
Franco, E.; Garcia-Recio, V.; Jiménez, P.; Garrosa, M.; Girbés, T.; Cordoba-Diaz, M.; Cordoba-Diaz, D. Endotoxins from a pharmacopoeial point of view. Toxins (Basel), 2018, 10(8), 331-339.
[http://dx.doi.org/10.3390/toxins10080331] [PMID: 30115887]
[http://dx.doi.org/10.3390/toxins10080331] [PMID: 30115887]
[10]
Valentini, S.; Santoro, G.; Baffetta, F.; Franceschi, S.; Paludi, M.; Brandini, E.; Gherardini, L.; Serruto, D.; Capecchi, B. Monocyte-activation test to reliably measure the pyrogenic content of a vaccine: An in vitro pyrogen test to overcome in vivo limitations. Vaccine, 2019, 37(29), 3754-3760.
[http://dx.doi.org/10.1016/j.vaccine.2018.10.082] [PMID: 30448065]
[http://dx.doi.org/10.1016/j.vaccine.2018.10.082] [PMID: 30448065]
[11]
Perdomo-Morales, R.; Pardo-Ruiz, Z.; Spreitzer, I.; Lagarto, A.; Montag, T. Monocyte activation test (MAT) reliably detects pyrogens in parenteral formulations of human serum albumin. ALTEX, 2011, 28(3), 227-235.
[http://dx.doi.org/10.14573/altex.2011.3.227] [PMID: 21993958]
[http://dx.doi.org/10.14573/altex.2011.3.227] [PMID: 21993958]
[12]
Hoffmann, S.; Peterbauer, A.; Schindler, S.; Fennrich, S.; Poole, S.; Mistry, Y.; Montag-Lessing, T.; Spreitzer, I.; Löschner, B.; van Aalderen, M.; Bos, R.; Gommer, M.; Nibbeling, R.; Werner-Felmayer, G.; Loitzl, P.; Jungi, T.; Brcic, M.; Brügger, P.; Frey, E.; Bowe, G.; Casado, J.; Coecke, S.; de Lange, J.; Mogster, B.; Naess, L.M.; Aaberge, I.S.; Wendel, A.; Hartung, T. International validation of novel pyrogen tests based on human monocytoid cells. J. Immunol. Methods, 2005, 298(1-2), 161-173.
[http://dx.doi.org/10.1016/j.jim.2005.01.010] [PMID: 15847806]
[http://dx.doi.org/10.1016/j.jim.2005.01.010] [PMID: 15847806]
[13]
Wunderlich, C.; Schumacher, S.; Kietzmann, M. Pyrogen detection methods: comparison of bovine whole blood assay (bWBA) and monocyte activation test (MAT). BMC Pharmacol. Toxicol., 2014, 15, 50.
[http://dx.doi.org/10.1186/2050-6511-15-50] [PMID: 25209100]
[http://dx.doi.org/10.1186/2050-6511-15-50] [PMID: 25209100]
[14]
Guidance for Industry Pyrogen and Endotoxins Testing. www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
[15]
Monocyte Activation Test. In European Pharmacopeia 9.0Council
of Europe: Strasbourg, France, 2017, pp. 193-194. ISNB 978-9-
2871-8133-6..
[16]
Moss, A.; Bourke, M.J.; Kwan, V.; Tran, K.; Godfrey, C.; McKay, G.; Hopper, A.D. Succinylated gelatin substantially increases en bloc resection size in colonic EMR: A randomized, blinded trial in a porcine model. Gastrointest. Endosc., 2010, 71(3), 589-595.
[http://dx.doi.org/10.1016/j.gie.2009.10.033] [PMID: 20189519]
[http://dx.doi.org/10.1016/j.gie.2009.10.033] [PMID: 20189519]
[17]
Deng, Y.; Zhu, Q.; Yu, B.; Zheng, M.; Jin, J. The effects of hypervolemic infusion on microcirculation perfusion of patients during laparoscopic colorectal surgery. Medicine (Baltimore), 2017, 96(45)e8612
[http://dx.doi.org/10.1097/MD.0000000000008612] [PMID: 29137091]
[http://dx.doi.org/10.1097/MD.0000000000008612] [PMID: 29137091]
[18]
Lai, C.W.; Starkie, T.; Creanor, S.; Struthers, R.A.; Portch, D.; Erasmus, P.D.; Mellor, N.; Hosie, K.B.; Sneyd, J.R.; Minto, G. Randomized controlled trial of stroke volume optimization during elective major abdominal surgery in patients stratified by aerobic fitness. Br. J. Anaesth., 2015, 115(4), 578-589.
[http://dx.doi.org/10.1093/bja/aev299] [PMID: 26385666]
[http://dx.doi.org/10.1093/bja/aev299] [PMID: 26385666]
[19]
Liolios, C.C.; Xanthopoulos, S.; Loudos, G.; Varvarigou, A.D.; Sivolapenko, G.B. Co-administration of succinylated gelatine with a (99m)Tc-bombesin analogue, effects on pharmacokinetics and tumor uptake. Nucl. Med. Biol., 2016, 43(10), 625-634.
[http://dx.doi.org/10.1016/j.nucmedbio.2016.07.005] [PMID: 27497631]
[http://dx.doi.org/10.1016/j.nucmedbio.2016.07.005] [PMID: 27497631]
[20]
Jin, Z-H.; Furukawa, T.; Sogawa, C.; Claron, M.; Aung, W.; Tsuji, A.B.; Wakizaka, H.; Zhang, M-R.; Boturyn, D.; Dumy, P.; Fujibayashi, Y.; Saga, T. PET imaging and biodistribution analysis of the effects of succinylated gelatin combined with L-lysine on renal uptake and retention of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in vivo. Eur. J. Pharm. Biopharm., 2014, 86(3), 478-486.
[http://dx.doi.org/10.1016/j.ejpb.2013.11.006] [PMID: 24316338]
[http://dx.doi.org/10.1016/j.ejpb.2013.11.006] [PMID: 24316338]
[21]
Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: A review. Arab. J. Chem., 2015, 10, S1409-S1421.
[http://dx.doi.org/10.1016/j.arabjc.2013.04.016]
[http://dx.doi.org/10.1016/j.arabjc.2013.04.016]
[22]
AlOthman, Z.A.; Rahman, N.; Siddiqui, M.R. Review on pharmaceutical impurities, stability studies and degradation products. Rev.Adv.Sci.Eng, 2013, 2, 155-166.
[http://dx.doi.org/10.1166/rase.2013.1039]
[http://dx.doi.org/10.1166/rase.2013.1039]
[23]
Rahman, N.; Azmi, S.N.H.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: An integrated approach. Accredit. Qual. Assur., 2006, 11, 69-74.
[http://dx.doi.org/10.1007/s00769-006-0095-y]
[http://dx.doi.org/10.1007/s00769-006-0095-y]
[24]
Maggio, R.M.; Calvo, N.L.; Vignaduzzo, S.E.; Kaufman, T.S. Pharmaceutical impurities and degradation products: uses and applications of NMR techniques. J. Pharm. Biomed. Anal., 2014, 101, 102-122.
[http://dx.doi.org/10.1016/j.jpba.2014.04.016] [PMID: 24853620]
[http://dx.doi.org/10.1016/j.jpba.2014.04.016] [PMID: 24853620]
[25]
Wang, C.; Dong, S.; Zhao, H. A novel monocyte-based pyrogen test based on the mechanism of human fever reaction. Curr. Pharm. Anal., 2016, 12(3), 227-233.
[http://dx.doi.org/10.2174/1573412912666151211200203]
[http://dx.doi.org/10.2174/1573412912666151211200203]
[26]
Wang, M.; Dong, S.; Shao, H.; Wang, C.; Chen, G. The optimization of HL60-IL6 assay and its application in the pyrogen detection of monoclonal antibody. Curr. Pharm. Anal., 2018, 16(3), 319-327.
[http://dx.doi.org/10.2174/1573412914666180627142302]
[http://dx.doi.org/10.2174/1573412914666180627142302]
[27]
Al-Shehri, M.; El-Gendy, M.; Darwish, I. Development of specific new ELISA for bioanalysis of cetuximab: A monoclonal antibody used for cancer immunotherapy. Curr. Pharm. Anal., 2018, 14(5), 519-525.
[http://dx.doi.org/10.2174/1573412914666180220122641]
[http://dx.doi.org/10.2174/1573412914666180220122641]
[28]
Veerapandian, M.; Yun, K. Study of atomic force microscopy in pharmaceutical and biopharmaceutical interactions - A Mini Review. Curr. Pharm. Anal., 2009, 5(3), 256-268.
[http://dx.doi.org/10.2174/157341209788922020]
[http://dx.doi.org/10.2174/157341209788922020]
[29]
Oliva, A.; Farina, J.; Llabres, M. New trends in analysis of biopharmaceutical products. Curr. Pharm. Anal., 2007, 3(4), 230-248.,
[http://dx.doi.org/10.2174/157341207782418811]
[http://dx.doi.org/10.2174/157341207782418811]
Article Metrics
5
1