Issues in the development of medical products based on human plasma

Josić, Djuro; Schulz, Petra; Biesert, Lothar; Hoffer, Lutz; Schwinn, Horst; Kordis-Krapez, Mira; Štrancar, Aleš

doi:10.1016/s0378-4347(97)00130-8

Cited by 19 publications

(3 citation statements)

References 31 publications

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“…The model of gradient HPLC separations of proteins was applied to develop the theoretical and practical views of HPMC. − The physical and chemical properties of protein macromolecules, which explain their behavior in dynamic separation, gave the possibility of transferring rather easily the separation process onto thin throughput layers with an adsorption functionality identical to that of sorbents used in conventional HPLC. − The experimental comparison of protein behavior under HPLC and HPMC conditions showed that the general principles of gradient chromatography can be applied in both cases. − The advantages of the later are separation of proteins (including affinity HPMC) in the seconds time range, low-pressure drop, and high-flow unaffected dynamic binding capacity. − Experience in this area recently allowed for development of an original theoretical model of protein separation by the HPMC method called the “one-step desorption process”…”

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confidence: 99%

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High-Performance Membrane Chromatography of Small Molecules

et al. 1999

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High-performance membrane chromatography (HPMC) proved to be a very efficient method for fast protein separations. Recently, it was shown to be applicable also for the isocratic chromatography of plasmid DNA conformations. However, no study about the separation of small molecules has been performed until now. In this work, we investigated the possibility of gradient and isocratic HPMC of small molecules with Convective Interaction Media disks of different chemistries and tried to explain the mechanism that enables their separation. We demonstrated that it is possible to achieve efficient separations of oligonucleotides and peptides in the ion-exchange mode as well as the separation of small hydrophobic molecules in the reversed-phase mode. It was shown that similar peak resolution can be provided in both gradient and isocratic modes.

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confidence: 99%

“…[22][23][24][25] The advantages of the later are separation of proteins (including affinity HPMC) in the seconds time range, low-pressure drop, and high-flow unaffected dynamic binding capacity. [26][27][28][29][30][31] Experience in this area…”

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confidence: 99%

High-Performance Membrane Chromatography of Small Molecules

et al. 1999

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“…The chromatography process physically separates virus particles from the product based on size, charge, density, binding affinity, and other differences between virus and product [41][42][43]. To evaluate effectiveness of the DEAE-toyopearl 650M anion-exchange column chromatography step in partitioning viruses, the elution profile of non-enveloped viruses through chromatography was assessed (Table 5).…”

Section: Inactivation Of Enveloped Viruses Through S/d Treatmentmentioning

confidence: 99%

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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