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Quantitative Real-Time PCR of Porcine Parvovirus as a Model Virus for Cleaning Validation of Chromatography during Manufacture of Plasma Derivatives  

Kil Tae Gun (Department of Biological Sciences, Hannam University)
Kim Won Jung (Department of Biological Sciences, Hannam University)
Lee Dong Hyuk (Department of Biological Sciences, Hannam University)
Kang Yong (Central Research Center, Green Cross Co.)
Sung Hark Mo (Central Research Center, Green Cross Co.)
Yoo Si Hyung (Blood Products Division, Biologics Evaluation Department Korea Food and Drug Administration)
Park Sue-Nie (Blood Products Division, Biologics Evaluation Department Korea Food and Drug Administration)
Kim In Seop (Department of Biological Sciences, Hannam University)
Publication Information
Korean Journal of Microbiology / v.41, no.3, 2005 , pp. 216-224 More about this Journal
Abstract
Chromatography has now been used successfully to provide the requisite purity for human plasma-derived biop-harmaceuticals such as coagulation factors and immunoglobulins. Recently, increasing attention has been focused on establishing efficient cleaning procedures to prevent potential contamination by microorganisms as well as carry-over contamination from batch to batch. The purpose of present study was to develop a cleaning validation system for the assurance of virus removal and/or inactivation during chromatography process. In order to establish an assay system for the validation of virus clearance during chromatography cleaning process, a quantitative real-time PCR method for porcine parvovirus(PPV) was developed, since PPV, a model virus for human parvovirus B19, has a high resistance to a range of physico-chemical treatment. Specific primers for amplification of PPV DNA was selected, and PPV DNA was quantified by use of SYBR Green I. The sensitivity of the assay was calculated to be 1.5 $TCID_{50}/ml$. The established real-time PCR assay was successfully applied to the validation of PPV removal and cleaning during SP-Sepharose cation chromatography for thrombin purification and Q-Sepharose anion chromatography for factor VIII purification. The comparative results obtained by real-time PCR assay and infectivity titrations suggested that the real-time PCR assay could be a useful method for chromatography cleaning validation and that it could have an additive effect on the interpretation and evaluation of virus clearance during the virus removal process.
Keywords
cleaning validation; plasma derivatives; porcine parvovirus; real-time PCR; virus inactivation;
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