著者

村井 活史 浦久保 知也 西田 靖武 洪 苑起 菅原 敬信 岡村 元義 小田 昌宏 川俣 治 小杉 公彦 塩見 哲次 高橋 英晴 殿守 俊介 林 秀樹 丸山 裕一

出版者

一般社団法人日本PDA製薬学会

雑誌

日本PDA学術誌 GMPとバリデーション (ISSN:13444891)

巻号頁・発行日

vol.9, no.1, pp.6-31, 2007 (Released:2008-06-06)

被引用文献数

1

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The Bio-virus safety committee, one of the committees of the Parental Drug Association Japan (PDA Japan), has discussed various concerns on biopharmaceuticals from scientific, technical and regulatory perspective. One of the most significant concerns is the risk of viral contamination into the products. This risk should be addressed, as required per the international regulations, by minimizing to use raw materials sourced from animal origin and by performing viral clearance studies in order to evaluate capability of purification processing to reduce and/or inactivate known and/or adventitious viruses. The Bio-virus safety Committee has reported the conclusions of discussion how to prepare and qualify cell bank system as one of raw materials and how much Log Reduction Value (LRV) should be targeted in virus clearance studies in the annual conference of the PDA Japan in 20051). The Bio-virus safety committee has discussed the practical experimental procedures for viral clearance studies since 2006 and reported the conclusions in the annual conference of the PDA Japan in 2007. In this report, standardized and practical experimental procedures for viral clearance studies are shown, considering not only requirements for submission to regulatory agencies but also experimental technique. In addition, trouble shooting based upon experiences of the members, information regarding Contract Research Organizations (CROs), reference of international guidelines, and worksheets of viral clearance study are provided.

著者

川俣 治

出版者

新潟医学会

雑誌

新潟医学会雑誌 = 新潟医学会雑誌 (ISSN:00290440)

巻号頁・発行日

vol.111, no.10, pp.633-646, 1997-10

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In order to detect enterovirus and rhinovirus sequences as separately for the virus genera by single test of RT-PCR (reverse transcription-polymerase chain reaction), two sets of the primers were prepared covering the 5'-NTR (nontranslated region) to the VP4 in the virus genome for amplification. The sequences selected for detection included a deletion of ca. 120 b (bases) stretch in the rhinovirus genome so as to get the products separate in the electrophoretic mobilities for each virus groups. The first set of the primers consisted of P3 (5'-GGCCCCTGAATGCGGCTAAT-3') and P5 (3'-GTTCTGGGATCATTTAAGTG-5') and the second was of P4 (5'-ACTTTGGGTGTCCGTGTTTC-3') and P5;the P3 and P4 (for a closer site to the P5 compared to the P3 site) were complementary to the sequences in the 5'-NTR of 95~100% homology and P5 being in the VP4 region complementary to the sequence of 60~90% homology through the two virus groups, each. By considering the relatively low homology in the counterpart site, the P5 primer was employed for initiation of the reverse transcription at a low temperature of 37℃ for promoting the primer annealing to the template RNA. When applied to the prototype strains, the P3-P5 primers gave a single band equivalent to 460 b DNA for the enteroviruses (43/44 serotypes) and that of 340 b DNA for the rhinoviruses (8/8 serotypes), thus enabling to easily discriminate the two virus groups on the separate mobilities of the products. Similarly, the products by the P4-P5 primers were of 340 b and 220 b DNAs for enteroviruses (43/44 serotypes) and rhinoviruses (8/8 serotypes), respectively, again being of easy discrimination of the virus groups. Of these experiments, authenticity of the products was confirmed by base sequence analysis with selected product samples from the experimental groups. The primers prepared were also compared for the efficiencies of virus detection in the clinical specimens with the tissue culture method for virus isolation. Positive ratios resulted were 65/96 by the RT-PCR and 54/96 by the tissue culture method. The primers thus proved effective for rapid and discriminative detection of enteroviruses and rhinoviruses to the laboratory diagnosis.

著者

川口 竜二 竹村 一男 川俣 治 小笠 詩子

出版者

Japanese Electrophoresis Society

雑誌

生物物理化学 (ISSN:00319082)

巻号頁・発行日

vol.40, no.6, pp.299-303, 1996-12-15 (Released:2009-03-31)

著者

浦久保 知也 大場 徹也 岡村 元義 金田 伸一 川俣 治 塩見 哲次 重松 弘樹 菅谷 真二 菅原 敬信 曲田 純二 丸山 裕一 元木 政道

出版者

一般社団法人日本PDA製薬学会

雑誌

日本PDA学術誌 GMPとバリデーション (ISSN:13444891)

巻号頁・発行日

vol.10, no.2, pp.23-36, 2008 (Released:2009-12-04)

参考文献数

6

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The Bio-Virus Safety Committee (BV-Committee), one of the committees of the Parental Drug Association Japan (PDA Japan), has discussed various concerns on biopharmaceuticals from scientific, technical and regulatory perspective. One of the most significant concerns is the risk of contamination of infectious agents into manufacturing process and products. This risk should be addressed, as required per the international regulations, by minimizing to use raw materials sourced from animal origin and by performing viral clearance studies in order to evaluate capability of purification process to reduce and/or inactivate known and/or adventitious viruses. BV-Committee reported the conclusions of discussion how to prepare and qualify cell bank system as one of raw materials and how much Log Reduction Value (LRV) should be targeted in virus clearance studies in the 13th annual conference of the PDA Japan in 2005 and published in the PDA Journal1). Since 2007, BV-Committee discussed the practical experimental procedures for viral clearance studies and reported the conclusions in the 14th annual conference of the PDA Japan in 2007 and reported in the PDA journal2). In the report, standardized and practical experimental procedures for viral clearance studies were proposed, considering not only requirements for submission to the regulatory agencies but also experimental technique. In addition, trouble shooting based upon the actual experience of the members, information regarding Contract Research Organizations (CROs), references of international guidelines, and worksheets for viral clearance study are provided.   Since 2008, BV-Committee has discussed how the Quality Risk Management (QRM) approach can be applied to manufacturing and quality control of biopharmaceuticals through a case study of a recombinant monoclonal antibody. The conclusion was presented in the 15th annual conference of the PDA Japan in 2008. In the case study, we supposed that viral contamination and residual process related impurities could be the source of quality risk. Risk assessment practice was performed, focusing on the following five categories, “Cell Banking”, “Cell Culture”, “Purification”, “Medium/Buffer Preparation” and “Viral Inactivation and Filtration”. In certain items, where the assessment showed higher risk, preventative measures to control the risk were discussed.