• Korean Journal of Microbiology
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• v.51 no.3
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• pp.199-208
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• 2015

Biologics and medical devices manufactured with bovine-derived raw materials have the risk of viral contamination. Therefore, viral validation study is essential to ensure the safety of the products. Bovine adenovirus type-1 (BAdV-1) is one of the common bovine viral pathogens. For quantitative detection of BAdV-1 during the manufacture of biologics and medical devices, a TaqMan probe real-time PCR method was developed. Specific primers and TaqMan probe for amplifying and detecting BAdV-1 DNA were designed. Specificity, limit of detection (LOD), and robustness of the method was validated according to international guideline on the validation of nucleic acid amplification tests for the pathogen detection. The sensitivity of the assay was found to be $7.44{\times}10^1\;TCID_{50}/ml$. The real-time PCR method was reproducible, very specific to BAdV-1, and robust. Moreover, the method was successfully applied to the validation of Chinese Hamster Ovary (CHO)-K1 cells artificially infected with BAdV-1, a commercial CHO master bank, and bovine type 1 collagen. The overall results indicate that this rapid, specific, sensitive, and robust assay can be reliably used for quantitative detection of BAdV-1 contamination during the manufacture of biologics and medical devices using bovine-derived raw materials.

• Bioindustry News
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• v.21 no.4
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• pp.7-24
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• 2008

• The Korean Journal of Applied Statistics
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• v.25 no.1
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• pp.125-138
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• 2012

Recent assessments of the biosimilarity of biologic products have received considerable global attention. A clinical trial should be conducted to assess the biosimilarity of a biosimilar product and a innovator biological product. In this paper we will describe several methods for the implementation of clinical trials and statistical analysis, a real international case and related international guidelines.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.309-318
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• 2000

우리나라에서는 1989년 1월 1일 이후 허가된 신약과 동일한 의약품을 제조하거나, 제제개선을 통하여 흡수율을 향상시키는 경우 등에 있어서 생물학적 동등성 시험을 실시하여 두 제제간의 생체이용률을 비교하도록 규정되어 있다. 다른 나라에서도 신약과 동일한 의약품을 허가 받고자 할 경우나 대체조제를 위한 복제의약품의 생산 시 생물학적 동등성 시험자료를 제출하도록 하고 있으며, 이에 따른 생물학적 동등성 시험 기준을 운영하고 있다. 최근 각국에서는 국제적 조화를 이룬 기준을 마련하고자 하는 추세이다. 현재 우리나라에서는 의약분업 실시에 따라 생물학적 동등성 시험의 중요성이 부각되고 있으며 국제적인 수준에 맞추어 관련 기준을 개정해야할 필요성이 대두되고 있다. 캐나다에서는 1992년에 처음 생물학적 동등성 시험 기준을 공표하여 평가하고 있다. 본 논문에서는 캐나다의 생물학적 동등성 시험 기준을 소개하여 현행 규정과 비교 검토함으로써 생물학적 동등성 시험 기준을 보다 과학적이고 윤리적이며 합리적인 규정으로 개정하기 위한 자료로 활용하고자 한다.

• Proceedings of the Korea Information Processing Society Conference
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• 2018.10a
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• pp.89-92
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• 2018

QbD(Quality by Design)는 제약분야에서 혁신적 신기술로 제조공정과 품질관리를 일원화하는 방법이다. QbD는 의약품의 품질을 높은 수준으로 향상시켜 제조공정 과정을 개선하여 효율성을 증대시키고 불량률 뿐만 아니라 공정 중 불필요한 장치의 가동을 최소화하여 비용을 절감시킬 수 있다. 본 논문은 제약분야에서 QbD 적용의 필요성에 따라 에지 컴퓨팅 기반 QbD 플렛폼 설계를 제안한다. 특히, 이 QbD 플렛폼을 통해 대조약과 시험약 간의 생물학적 동등성 의약품 제조에 필요한 실험설계방법을 획기적으로 개선하고자 한다. 이를 위해 본 논문은 먼저 QbD의 단계 중 실험설계법을 제형연구의 예를 들어 설명하고 본 논문이 계획한 QbD 플랫폼의 구조를 제안한다.

• Microbiology and Biotechnology Letters
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• v.36 no.3
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• pp.173-181
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• 2008

Bovine blood, cell, tissue, and organ are used as raw materials for manufacturing biologics such as biopharmaceuticals, tissue-engineered products, and cell therapy. Manufacturing processes for the biologics have the risk of viral contamination. Therefore viral validation is essential in ensuring the safety of the products. Bovine parvovirus (BPV) is one of the common bovine pathogens and has widely been known as a possible contaminant of biologics. In order to establish the validation system for the BPV safety of biologics, a real-time PCR method was developed for quantitative detection of BPV contamination in raw materials, manufacturing processes, and final products. Specific primers for amplification of BPV DNA were selected, and BPV DNA was quantified by use of SYBR Green 1. The sensitivity of the assay was calculated to be $1.3{\times}10^{-1}\;TCID_{50}/mL$. The real-time PCR method was validated to be reproducible and very specific to BPV. The established real-time PCR assay was successfully applied to the validation of Chinese hamster ovary (CHO) cell artificially infected with BPV. BPV DNA could be quantified in CHO cell as well as culture supernatant. Also the real-time PCR assay could detect $1.3{\times}10^0\;TCID_{50}/mL$ of BPV artificially contaminated in bovine collagen. The overall results indicated that this rapid, specific, sensitive, and robust assay can be reliably used for quantitative detection of BPV contamination during manufacture of biologics.

• Microbiology and Biotechnology Letters
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• v.36 no.1
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• pp.34-42
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• 2008

Bovine blood, cell, tissue, and organ are used as raw materials for manufacturing biologics such as biopharmaceuticals, tissue engineered products, and cell therapy. Manufacturing processes for the biologics using bovine materials have the risk of viral contamination. Therefore viral validation is essential in ensuring the safety of the products. Bovine viral diarrhoea virus (BVDV) is the most common bovine pathogen and has widely been known as a contaminant of biologics. In order to establish the validation system for the BVDV safety of biologics, a real-time RT-PCR method was developed for quantitative detection of BVDV contamination in raw materials, manufacturing processes, and final products. Specific primers for amplification of BVDV RNA was selected, and BVDV RNA was quantified by use of SYBR Green I. The sensitivity of the assay was calculated to be 1 $TCID_{50}/mL$. The rent-time RT-PCR method was validated to be reproducible and very specific to BVDV. The established real-time RT-PCR assay was successfully applied to the validation of Chinese hamster ovary (CHO) cell artificially infected with BVDV. BVDV RNA could be quantified in CHO cell as well as culture supernatant. Also the real-time RT-PCR assay could detect $10TCID_{50}/mL$ of BVDV artificially contaminated in bovine collagen.

• Microbiology and Biotechnology Letters
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• v.40 no.4
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• pp.339-347
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• 2012

Viral safety is an important prerequisite for clinical preparations of mammalian cell culture-derived biopharmaceuticals, because numerous adventitious viruses have been contaminated during the manufacturing process. In particular, Chinese hamster ovary (CHO) cells are highly susceptible to several RNA viruses including reovirus (Reo), bovine viral diarrhea virus (BVDV), and bovine parainfluenza virus (BPIV) and there have been reports of such viral contaminations. Therefore, viral detection during the CHO cell process is necessary to ensure the safety of biopharmaceuticals against viruses. In this study, a multiplex reverse transcription (RT)-PCR assay was developed and subsequently evaluated for its effectiveness as a means to simultaneously detect Reo, BVDV, and BPIV during the manufacture of cell culture-derived biopharmaceuticals. Specific primers for Reo, BVDV, and BPIV were selected, and a multiplex RT-PCR was optimized. The sensitivity of the assay for simultaneous amplification of all viral target RNAs was $7.76{\times}10^2\;TCID_{50}/ml$ for Reo, $7.44{\times}10^1\;TCID_{50}/ml$ for BVDV, and $6.75{\times}10^1\;TCID_{50}/ml$ for BPIV. The multiplex RT-PCR was proven to be very specific to Reo, BVDV, and BPIV and was subsequently applied to the validation of CHO cells artificially infected with each virus. It could detect each viral RNA from CHO cells as well as culture supernatants. Therefore, it was concluded that the multiplex RT-PCR assay can be applied to detection of the adventitious viruses during the manufacture of cell culture-derived biopharmaceuticals.

• The Microorganisms and Industry
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• v.20 no.1
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• pp.11-17
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• 1994

본 고에서는 리파제를 이용한 키랄약품의 합성 및 새로운 합성기술을 요약하고자 한다.

• 대한임상약리학회:학술대회논문집
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• 2000.04a
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• pp.11-12
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• 2000