• Journal of Microbiology
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• v.39 no.1
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• pp.67-73
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• 2001

A validation study was conducted to evaluate the efficacy and mechanism of the cryo-precipitation, monoclonal anti-FVIIIc antibody (mAb) chromatography, Q-Sepharose chromatography, and lyophilization steps involved in the manufacture of high purity factor VIII (GreenMono) from human plasma, in the removal and/or inactivation of hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and subjected to scale-down processes mimicking the manufacture of the high purity factor VIII concentrate. Samples were collected at each step and immediately titrated using a 50% tissue culture infectious dose (TCID$\_$50/) and then the virus reduction factors were evaluated. HAV was effectively partitioned from factor VⅢ during cryo-precipitation with the log reduction factor of 3.2. The mAb chromatography was the most effective step far removal of HAV with the log reduction factor of $\geq$4.3. HAV infectivity was not detected in the fraction of factor VⅢ, while most of HAV infectivity was recovered in the fractions of flow through and wash during mAb chromatography. Q-Sepharose chromatography showed the lowest efficacy for partitioning HAV with the log reduction factor of 0.7. Lyophilization was an effective step in inactivating HAV with the log reduction factor of 2.3. The cumulative lag reduction factor, $\geq$10.5, achieved for tile entire manufacturing process was several magnitudes greater than the potential HAV load of current plasma pools.

• Membrane Journal
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• v.30 no.1
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• pp.9-20
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• 2020

Membranes are used in most processes of biopharmaceutical production. It is used for pretreatment of other processes, separation of impurities in the process, virus removal, control of products concentration and buffer solution exchange. Virus filters play an important role in ensuring product efficacy and stability because viral contamination of biopharmaceuticals for humans is a sensitive issue that is directly related to serious clinical outcomes. Virus filters typically have complex multilayer structures made of various polymers such as surface-modified PVDF, PES, CRC. Depending on the manufacturer, filters have different pore structures and shapes, such as symmetric or asymmetric, and is used in the form of pleated membrane, flat sheets or hollow fibers. Virus filters are exclusively supplied by few foreign companies such as Asahi Kasei, Millipore, Pall and Sartorius. Replacing virus filters can be time consuming and expensive, including approval from regulatory agencies through validation. As localization has become important due to Japan's recent export regulations, it is necessary to increase the degree of technical independence.

• Journal of Microbiology
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• v.38 no.3
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• pp.187-191
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• 2000

A validation study was conducted to determine the efficacy of solvent/Detergent (S/D) inactivation and Q-Sepharose column chromatographic removal of the human immunodeficiency virus (HIV) during the manufacturing of a high purity antihemopilic factor VIII (GreenMono) from human plasma. S/D treatment using the organic solvent, tri (n-butyl) phosphate, and the detergent, Trition X-100, was a robust and effective step in eliminating HIV-1. The HIV-1 titer was reduced from an initial titer of 8.3 log10 TCID50 to undetectable levels within one minute of S/D treatment, HIV-1 was effectively partitioned form factor VIII during Q-Sepharose column chromatography with the log reduction factor of 4.1 . These results strongly assure the safety of GreenMono From HIV.

• Journal of Microbiology and Biotechnology
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• v.10 no.6
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• pp.858-864
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• 2000

The purpose of the present study was to examine the efficacy and mechanism of the fraction IV cold ethanol fractionation and pasteurization ($60^{\circ}C$ heat treatment for 10h) steps, involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of blood-born viruses. A variety of experimental model viruses for human pathogenic viruses, including the Bovine viral diarrhoea virus (BVDV), Bovine herpes virus (BHV), Murine encephalomyocarditis virus (EMCV), and Porcine parvovirus (PPV), were selected for this study. Samples from the relevant stages of the production process were spiked with the viruses, and the amount of virus in each fraction was then quantified using a 50% tissue culture infectious dose ($TCID_{50}$). The mechanism of reduction for the enveloped viruses (BHV and BVDV) during fraction IV fractionation was inactivation rather than partitioning, however, it was partitioning in the case of the non-enveloped viruses (EMCV and PPV). The log reduction factors achieved during fraction IV fractionation were ${\geq}6.9$ BHV, $\geq5.2$ for BBDV, 4.9 for EMC, and 4.0 for PPV. Pasteurization was found to be a robust and effective step in inactivating the enveloped viruses as well as EMCV. The log reduction factors achieved during pasteurization were $\geq7.0$ for BHV, $\geq6.1$ for BVDV, $\geq6.3$ for EMCV, and 1.7 for PPV. These results indicate that the production process for albumin has sufficient virus-reducing capacity to achieve a high margin for virus safety.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.65-68
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• 2004

The purpose of the present study was to examine the efficacy and mechanism of fraction IV cold ethanol fractionation and pasteurization (60$^{\circ}C$ heat treatment for 10 h), involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of the hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and the amount of virus in each fraction then quantified using a 50% tissue culture infectious dose (TCID$\_$50/). HAV was effectively partitioned from albumin during the fraction IV cold ethanol fractionation with a log reduction factor of 3.43. Pasteurization was also found to be a robust and effective step in inactivating HAV, where the titers were reduced from an initial titer of 7.60 log TCID$\_$50/ to undetectable levels within 5 h of treatment. The log reduction factor achieved during pasteurization was $\geq$4.76. Therefore, the current results indicate that the production process for albumin has sufficient HAV reducing capacity to achieve a high margin of virus safety.

• Korean Chemical Engineering Research
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• v.49 no.5
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• pp.588-593
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• 2011

The porcine epidemic diarrhea virus(PEDV) production yield in spinner flask cultures using Vero cells immobilized on microcarriers was improved by the selective adsorption of ammonium ions in a Carberry type bioreactor which was equipped with Phillipsite-Gismondine synthetic zeolite. Though the apparent cell growth seemed to be lower than that of control due to the aggregation of microcarriers between impeller shaft and the adsorbent, zeolite was found to not to be toxic to Vero cell, considering estimated glucose and lactate changes. Zeolite was observed to remove ammonium ions effectively in both steps of cell growth and virus production. In virus production, the virus titer with zeolite was two times higher than that without zeolite. Consequently, zeolite was found to be an ideal adsorbent for higher production of virus vaccine with the effective removal of ammonium ions.

• Journal of Korean Society on Water Environment
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• v.24 no.4
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• pp.423-429
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• 2008

Microfiltration (MF) and ultrafiltration (UF) processes for removal of particulate materials (i.e., turbidity, microorganisms and viruses) have been used to produce drinking water with higher quality. As membrane filtration technique has become widely applied for drinking water treatment, the importance of membrane integrity test (MIT) has also been increasingly emphasized. The results of pressure decay test (PDT) were presented in the paper to monitor membrane integrity. In this paper the PDT was carried out with deliberately-defected membrane fibers to evaluate the sensitivity of PDT on membrane fiber damage. Variation of pressure decay rate and removal rate were investigated to evaluate the impact of defection (defection ratio) and pore size of membrane. The membrane integrity could be successfully monitored by the PDT. The pressure decay rate varied from $0.002{\sim}0.189kg_f/cm^2hr$ with the initial pressure ranged from 0.2 to $1.0kg_f/cm^2hr$. Higher initial pressure which provided with higher pressure decay rate was preferred to evaluate the defection of membrane fiber. As for the particle removal rate, the Log Removal Rate (LRV) of kaolin solution decreased significantly from 3.78 to 2.31 when one fiber out of 3,200 fibers was cut. The membranes with different pore size were tested to evaluate virus removal efficiency. The virus removal rate of the MF membrane ($0.1{\mu}m$) was about 30% although the poliovirus was smaller than the pore size of the MF membrane, indicating that the removal rate was much lower than Korea Water Works Association (KWWA) certificate LRV of 1.5.

• 한국생물공학회:학술대회논문집
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• 2002.04a
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• pp.271-272
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• 2002

Newcastle disease virus (NDV) vaccines were produced from Vero cells by using lively attenuated virus strain. The MOI of 0.1.' serum concentration of 2%. initial pH of 8.0. and infection time of 3 days were found to be optimum conditions for vaccine production. The treatment of polycation enhanced the virus production. When ascorbic acid was added as an antioxidant, NDV production was also enhanced. Utilization of $CaCl_2$ showed an inhibitory effect on the propagation of NDV. It was also found the ammonium ion concentration higher than 4mM inhibited virus production. Thus ammonium ion removal system was tried for the efficient production of NDV vaccine.

• Journal of Embryo Transfer
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• v.1 no.1
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• pp.16-27
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• 1986

Based on the current importing and exporing regulations for disease control of embryo transfer, some important microorganisms and their control possibilities are reviewed. The results reviewed were sumrnarized as follows: 1. Regulations regarding to the import of embryos vary between importing and exporting countries, but exporting countries examine the donor and embryos for the heaith certification by the requirements of importing countries. 2. Organisms that infect the gametes are 5 kinds of viruses and the diseases caused by them could not be controlled or eradicated using embryo transfer. 3. Organisms that do not infect the gametes are 4 kinds of viruses and the causal organisms are potential candidates for control or eradication by embryo transfer. 4. Organisms that penetrate the zona pellucida and infect the embryo are 6 kinds of viruses including bovine viral diarrhea virus. 5. Organisms that cannot penetrate the zona pellucida or do not infect the embryo are 15 kinds of viruses and the removal from their contaminations are recommended by proper washing procedure and antisera treatment. Bovine and porcine parvovirus, porcine pseudorabies virus and vesicular stomatitis virus are included in these organisms. 6. Bovine embryos that artificially exposed to various pathogenic organisms such as bovine herpes virus, IBR virus, bluetongue virus, bovine viral diarrhea virus and Brucella abortus in vitro are discussed about their infection by several treatments.

• Convergence Security Journal
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• v.2 no.2
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• pp.39-47
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• 2002

To recently with the love-letter and Back Orifice the same Worm-virus, with the Trojan and the Linux-virus back against the new species virus which inside and outside of the country to increase tendency the malignant new species virus which is the possibility of decreasing the damage which is enormous in the object appears and to follow a same network coat large scale PC is being quicker, it disposes spontaneously to respect, applied an artificial intelligence technique the research against the next generation malignant computer virus of new form is demanded. Will reach and to respect it analyzes the digital immunity system of the automatic detection which is quick against the next generation malignant virus which had become unconfirmed and the foreign countries which has an removal function.