• Journal of Microbiology
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• 제39권1호
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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.

• 멤브레인
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• 제30권1호
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• pp.9-20
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• 2020

바이오 의약품 생산과정의 대부분 공정에서 분리막이 사용되고 있다. 분리막 공정은 다른 공정의 전처리, 공정 자체의 불순물 분리, 바이러스 제거, 목표 생성물 농도 조절 및 완충 용액 교환 등에 사용된다. 인체에 사용하는 바이오 의약품의 바이러스 오염은 심각한 임상 결과와 직결되는 민감한 문제이기 때문에 바이러스 필터는 제품의 효능과 안정성을 보장하기 위해 중요한 역할을 한다. 바이러스 필터는 일반적으로 표면 개질된 PVDF, PES, CRC 등 다양한 고분자로 만들어진 복합다층 구조를 가지고 있다. 제조업체에 따라 대칭(symmetric) 또는 비대칭(asymmetric) 등 다른 기공 구조와 형태를 가지고 있으며, 주름막, 평판 시트 또는 중공사 형태로 사용된다. 바이러스 필터는 Asahi Kasei 를 비롯해 Millipore, Pall, Sartorius 등 몇몇 해외 업체들이 독점적으로 국내에 공급하고 있다. 바이러스 필터를 대체하려면 검증작업을 통해 규제기관의 승인을 받는 등 상당한 시간과 비용이 소요된다. 최근 일본의 수출규제로 국산화가 중요해진 만큼 제거 성능 고도화 등 선제적으로 기술자립도를 높여가야 한다.

• Journal of Microbiology
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• 제38권3호
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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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• 제10권6호
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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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• 제9권1호
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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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• 제49권5호
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• pp.588-593
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• 2011

미립담체에 고정된 Vero 세포를 이용한 돼지유행성설사병 바이러스 백신의 생산성을 향상시키기 위하여 Phillipsite-Gismondine synthetic zeolite가 투석막에 충진된 Carberry type 생물반응기를 사용하여 암모늄 이온을 선택적으로 흡착하였다. Impeller shaft 및 흡착제 사이에 응집된 미립담체 때문에 세포 성장이 감소하는 것으로 보이나, 포도당 소모량과 젖산 생성량의 비교를 통해 판단 할 때 zeolite는 세포에 독성을 나타내지 않았다. 배양배지로부터 암모늄 이온을 제거함으로써 세포성장 및 바이러스 생산 두 단계 모두가 크게 개선되었다. 바이러스 생산에 있어서는 암모늄 이온 제거에 의해 대조군과 비교하여 바이러스 역가가 2배 이상 향상되었다. 연구결과 zeolite는 암모늄 이온을 효과적으로 흡착제거하여 바이러스 백신의 생산성을 높일 수 있는 이상적인 흡착제임을 확인하였다.

• 한국물환경학회지
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• 제24권4호
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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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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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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.

• 한국수정란이식학회지
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• 제1권1호
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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.

• 융합보안논문지
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• 제2권2호
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• pp.39-47
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• 2002

최근에는 러브레터 ,백오리피스와 같은 웜바이러스, 트로이목마, 리눅스바이러스 등과 같은 네트워크 상의 대규모 PC를 대상으로 막대한 피해를 줄 수 있는 악성 신종 바이러스가 출현함에 따라 국내외적으로 증가추세에 있는 신종 바이러스에 대하여 보다 신속하고 능동적으로 대처하기 위해서는 인공지능기법을 적용한 새로운 형태의 차세대 악성 컴퓨터바이러스에 대한 연구가 요구된다. 이를 위해서 미확인된 차세대 악성 바이러스에 대한 신속한 자동탐지 및 제거기능을 갖는 해외의 디지털 면역시스템을 분석한다.