Removal and inactivation of hepatitis A virus during manufacture of urokinase from human urine

Kim, In Seop; Choi, Yong Whan; Lee, Sung Rae; Kang, Yong; Lee, Kyung Myung; Park, Dae Han; Woo, Han Sang; Lee, Soungmin

doi:10.1007/bf02933518

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…The most widely used HAV strain in virus‐reduction studies is HM175, in particular the two cytopathogenic variants HM175/18f and HM175/24a, and previously published results showed that a mixed profile of virion populations was obtained for the related noncytopathic p16HM175 variant, depending on the HAV variant and cell line used for stock production . Through isopycnic gradient centrifugation, it was shown in the current work that HAV stocks, which were produced in BSC‐1 cells using typical virus stock‐production techniques, contained either a mixed population of LE and NLE particles (for HM175/18f) or solely LE virions (for HM175/24a), irrespective whether the harvest protocol included cell lysis or the use of cell culture supernatant alone.…”

Section: Discussionmentioning

confidence: 64%

“…Because HAV has historically been transmitted by plasma‐derived products, the use of HAV in virus reduction (i.e., inactivation and removal) studies, which are the basis for an evaluation of the virus safety profile of plasma‐derived medicinal products, is specifically required for plasma‐derived coagulation factor concentrates . HAV has therefore been widely used as a relevant target virus, as well as a model virus, in validation studies of many human plasma‐derived products …”

mentioning

confidence: 99%

“…In light of these reports, a closer characterization of the HAV stocks that are used in virus reduction studies has become necessary, as these need to be a true representative of the target virus. HM175, and in particular the HM175/18f and HM175/24a variants of this HAV strain, are commonly used in virus‐reduction studies . The two cell lines most frequently used for propagation of HAV stocks are BSC‐1 and FRhK4, and the choice of production cell line, the HAV variant and the method of virus stock harvest are the main parameters that might affect virus particle morphology and thus the properties of the virus stock.…”

mentioning

confidence: 99%

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A nonenveloped virus with a lipid envelope: hepatitis A virus as used in virus‐reduction studies

Kapsch¹,

Farcet²,

Antoine³

et al. 2017

Transfusion

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BACKGROUND Recently, a quasi‐lipid–enveloped (LE) form of the traditionally nonlipid‐enveloped (NLE) hepatitis A virus (HAV) was described in human serum and cell culture‐derived HAV stocks. This discovery challenges the understanding of HAV reduction in virus clearance studies of plasma products, which were performed under the premise of an NLE nature of this virus. Here, the presence of LE particles in HAV stocks used for reduction studies was verified, and the hypothesis that LE and NLE particles might contribute to the differential heat sensitivity of HAV variants during heat treatment of human serum albumin was evaluated. STUDY DESIGN AND METHODS Cell culture lysates and supernatants of two cytopathic HAV variants, HM175/18f and HM175/24a, were characterized for their LE and NLE particle content by isopycnic gradient centrifugation. The obtained fractions were characterized for relative infectivity and then subjected to heat treatment (58.0 ± 1.0°C for 590 ± 10 minutes) in 12.5% human serum albumin to investigate their respective heat sensitivity. RESULTS Preparations of the two HAV variants contained either LE particles (HM175/24a) or LE and NLE particles (HM175/18f) with equivalent specific infectivity. For HM175/18f, heat sensitivity of LE and NLE fractions did not differ significantly, and inactivation of the whole virus stock was identical to the NLE particle inactivation profile, whereas the HM175/24a variant was more heat sensitive. CONCLUSION The results indicate that, in heat‐treatment studies, the LE or NLE HAV phenotype is less important than the choice of HAV variant, and the most heat‐resistant HM175/18f should be used.

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Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A nonenveloped virus with a lipid envelope: hepatitis A virus as used in virus‐reduction studies

Kapsch¹,

Farcet²,

Antoine³

et al. 2017

Transfusion

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“…These results indicate that the Viresolve NFP filtration process was a robust and effective method for removal of viruses from factor IX preparations. In previous reports, it has also been shown that the Viresolve NFP filtration process is a robust and effective method for removal of viruses from urokinase preparations [32,47].…”

Section: Removal Of Viruses Through Viresolve Nfp Filtrationmentioning

confidence: 95%

Removal and inactivation of viruses during the manufacture of a high-purity antihemophilic factor IX from human plasma

Kim

Bae

Sung

et al. 2009

Biotechnol Bioproc E

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The purpose of this study was to evaluate the efficacy and mechanisms of the solvent/detergent (S/D) treatment, DEAE-toyopearl 650M anion-exchange column chromatography, heparin-sepharose 6FF affinity column chromatography, and Viresolve NFP filtration steps employed in the manufacture of high-purity antihemophilic factor IX (GreenNine VF) from human plasma, with regard to removal and/or inactivation of blood-borne viruses. A variety of experimental model viruses for human pathogenic viruses, including human immunodeficiency virus (HIV), bovine herpes virus (BHV), bovine viral diarrhoea virus (BVDV), hepatitis A virus (HAV), murine encephalomyocarditis virus (EMCV), and porcine parvovirus (PPV), were all selected for this study. Samples from relevant stages of the production process were spiked with each virus and subjected to scale-down processes mimicking the manufacture of high-purity factor IX. Samples were collected at each step, immediately titrated using a 50% tissue culture infectious dose (TCID 50 ), and virus reduction factors were evaluated. S/D treatment using the organic solvent, tri (n-butyl) phosphate (TNBP), and the detergent, Tween 80, was a robust and effective step in inactivation of enveloped viruses. Titers of HIV, BHV, and BVDV were reduced from the initial titer of 6.06, 7.72, and 6.92 log 10 TCID 50 , respectively, reaching undetectable levels within 1 min of S/D treatment. DEAE-toyopearl 650M anion-exchange column chromatography was found to be a moderately effective step in the removal of HAV, EMCV, and PPV with log reduction factors of 1.12, 2.67, and 1.38, respectively. Heparin-sepharose 6FF affinity column chromatography was also moderately effective for partitioning BHV, BVDV, HAV, EMCV, and PPV with log reduction factors of 1.55, 1.35, 1.08, 1.19, and 1.61, respectively. The Viresolve NFP filtration step was a robust and effective step in removing all viruses tested, since HIV, BHV, BVDV, HAV, EMCV, and PPV were completely removed during the filtration step with log reduction factors of ≥ 5.51, ≥ 5.76, ≥ 5.18, ≥ 5.34, ≥ 6.13, and ≥ 4.28, respectively. Cumulative log reduction factors of HIV, BHV, BVDV, HAV, EMCV, and PPV were ≥ 10.52, ≥ 12.07, ≥ 10.49, ≥ 7.54, ≥ 9.99, and ≥ 7.24, respectively. These results indicate that the production process for GreenNine VF has a sufficient virus reduction capacity for achievement of a high margin of virus safety. © KSBB hÉóïçêÇëW=~åíáÜÉãçéÜáäáÅ=Ñ~Åíçê=fuI=îáê~ä=áå~Åíáî~íáçå=~åÇLçê=êÉãçî~äI=äçÖ=êÉÇìÅíáçå=Ñ~ÅíçêI=îáêìë=ë~ÑÉíó= = = = =

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Enhanced virus safety of a solvent/detergent-treated antihemophilic factor IX concentrate by dry-heat treatment

Shin

Choi

Sung

et al. 2006

Biotechnol. Bioprocess Eng.

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Removal and inactivation of hepatitis A virus during manufacture of urokinase from human urine

Cited by 6 publications

References 16 publications

A nonenveloped virus with a lipid envelope: hepatitis A virus as used in virus‐reduction studies

A nonenveloped virus with a lipid envelope: hepatitis A virus as used in virus‐reduction studies

Removal and inactivation of viruses during the manufacture of a high-purity antihemophilic factor IX from human plasma

Enhanced virus safety of a solvent/detergent-treated antihemophilic factor IX concentrate by dry-heat treatment

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