著者

宇田 明史 寺田 勝英

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.8, no.2, pp.94-105, 2006 (Released:2008-02-01)

著者

モニカ ケファート

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.4, no.2, pp.85-98, 2002 (Released:2006-07-18)

著者

川村 邦夫

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.8, no.1, pp.2-17, 2006 (Released:2007-05-10)

参考文献数

7

被引用文献数

1

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Pharmaceutical Industry in Japan has made an fairly advancement since 1980s. In the course of the advancement, GMP played an important role, which has close relations with the development particularly, in CMC (Chemistry and Managing Control) and pre-approval inspection. In this paper, relationship between GMP and the development of pharmaceuticals has been discussed through the author's experiences. In 1980s, Takeda developed three kinds of Cephem-antibiotics in Japan, however, failed to launch them in USA due to the delay of their development. The delay was partly caused by GMP and regulatory procedures to FDA. In the next decade, Takeda has made a great success in developing LUPRON DEPOT, a drug of prostatic cancer and other new pharmaceuticals. These successes have been attributed to the well designed manufacturing process based on GMP. The complex aseptic processes have been designed and validated based on the current GMP. As the next new product, Aripiprazole (ABILIFYTM), a drug for schizophrenia, developed by Otsuka was successfully launched in USA by use of an alternative facility located in Japan, which was approved by FDA. The facility took a place of a problematic facility located in other country. Both of the products became blockbuster products in 2000s. Next to these successes, bio-product, which is now under development has encountered with several problems to overcome. Some of them are GMP and how to keep consistency from the initial stage of development to the stage of industrial production. These would be overcome in near future by taking GMP and consistency into account.

著者

石井 明子 橋井 則貴 松本 真理子 香取 典子 新井 進 粟津 洋寿 磯野 哲也 井上 友美 永座 明 大山 幸仁 奥村 剛宏 梶原 大介 田熊 晋也 丹下 浩一 塚原 正義 筒井 麻衣子 寺島 伊予 中川 泰志郎 服部 秀志 林 慎介 原 芳明 松田 博行 村上 聖 矢野 高広 巌倉 正寛 大政 健史 川崎 ナナ 広瀬 明彦

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.19, no.2, pp.15-29, 2017 (Released:2017-12-21)

参考文献数

17

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The use of single-use systems has been getting more popular in biologics manufacturing. Utilization of this novel technology enables the efficient manufacturing, including prevention of cross contamination, flexibility to manufacture multiple products, and elimination of the need for cleaning and steam sterilization including those validations. In order to ensure the quality and stable supply of biologics, appropriate risk management considering the characteristics of the system is necessary. However, there is no regulatory document describing the examples or recommendations on it. In 2015, we published the White paper of “Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics” in AAPS PharmSciTech, which was a fruit of discussion in the research group consisting of Japanese pharmaceutical manufacturers, single-use suppliers, academia and regulatory agencies. This review introduces the contents of the White paper with some revision reflecting the comments on it as well as the discussion in our research group after publishing the paper. The basic concept is consistent with ICH guideline on quality risk management. Here we describe the points to consider in risk assessment as well as in risk control when single-use systems are used in biologics manufacturing.

著者

谷本 和仁 越田 一朗 小久保 護

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.19, no.2, pp.45-55, 2017 (Released:2017-12-26)

参考文献数

10

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Aseptic processing or manufacturing is a method of manufacture in which microorganisms are excluded from the production environment and thereby prevented from entering the product. It has been recognized for decades and humans working in aseptic environments were the only significant source of contamination and therefore posed the greatest risk to both successful production of heat labile products and to the patient. Over the last two decades, there has been a technological evolution in aseptic processing which has greatly increased patient safety by dramatically reducing the risk of microbial contamination in aseptic processing. The improvements that have occurred in aseptic processing arise from two principal technological features. The first of these is the use of isolator technology and the second is the introduction of effective machine automation and robotics. Isolators have reduced contamination risk by effectively separating the human technician from the aseptic environment. Because isolators are an unmanned environment, which is much smaller in volume than a conventional manned clean room, they can be decontaminated in a manner that effectively eliminates microbial contamination of all kinds. The isolator after sporicidal decontamination is effectively a microorganism free environment. The capabilities of the isolator have been further enhanced by the application of robots and other forms of automation. An important recent innovation is the introduction of robotics that could be built into isolator systems and decontaminated in place. These specialized robots along with machine automation have further reduced contamination risk and at the same time eliminated the possibility of technician error. The modern isolator system is very well suited to meeting the cell culture requirements necessary for the production of cytotherapeutics, and as a result cell culture isolators are proving to be the best option for the production of many regenerative medicine products.

著者

Thomas Thorpe 玉澤 寛史

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.16, no.2, pp.29-37, 2014 (Released:2014-09-23)

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無菌充填に定期的に使用する容器・栓の洗浄及び滅菌・脱パイロジェン処理設備を導入してバリデーションを実施し,維持,稼働させることには相当な人的,財務的,及びフロアスペース等の資源を必要とするものであるが,小規模の医薬品開発においては,より効率的な別の資源配分をすることが可能である。本稿において著者らは,画期的な包装済み無菌充填キットである Ready-to-Fill® が,如何に cGMP に準拠して製造された無菌充填に適した製品であるかについて述べると共に,あらゆる規模の製薬企業及び医療機関に対して Ready-to-Fill® が提供できる様々なベネフィットを示す。

著者

古賀 裕香里

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.16, no.1, pp.1-8, 2014 (Released:2014-06-05)

参考文献数

9

著者

廣野 善昭

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.2, no.2, pp.109-131, 2000 (Released:2006-07-29)

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This report introduces GMP guidance and inspection activities in Yamaguchi Prefecture, Japan. There are 21 manufacturing sites in Yamaguchi Prefecture, Japan, in which 431 pharmaceuticals are being manufactured. Among them, 189 products are active pharmaceutical ingredients. Half of the active pharmaceutical ingredients manufactured are exported. There are 5 inspectors for GMP in Yamaguchi Prefecture. All of manufacturing sites and products are inspected during 5 years. Before conducting site inspection, thorough document surveillance is performed. That surveillance contains physical characteristics, manufacturing methods, critical processes, and critical quality attributes of the product. During document surveillance, ambiguous points are clarified by communication with manufacturers. After the document surveillance, usually 2 inspectors visit the manufacturing site for two days, and perform the inspection based on the preliminary established inspection check list. Observed results are classified to 1) suggestion, 2) item(s) to be further considered, 3) item(s) to be corrected. Results of these inspections have been introduced in this report by classified to the above three categories.

著者

本多 大地 Frithjof HOLTZ Najib SEHAT

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.14, no.1, pp.11-15, 2012 (Released:2013-01-26)

参考文献数

19

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A thousand different excipients can be used when formulating pharmaceuticals and, as a rough estimate, excipients can comprise more than 90% of a medicinal product's weight. Excipients are no longer characterized as simple inert additives to the API, and the need for stringent, quality management of excipients has grown rapidly. In 2010, FDA noted five drug recalls due to dissolution failures ascribed to excipients. In one case, FDA issued an import alert and an advisory to drug and dietary supplement manufacturers warning of high levels of peroxide in the excipient crospovidone manufactured in China. In the warning, FDA explained that drug manufacturers who used excipients containing high levels of peroxides would observe a loss of drug potency and the formation of excessive impurities during the product's shelf life. This article discusses how the supplier of pharmaceutical raw materials should take a central role in ensuring excipient quality.

著者

須藤 浩孝 伴 和敏 西脇 健二 河本 裕司 森 淳英 迫 和博 岡本 隆太 稲毛 亮太 川北 裕司 松岡 智生 今井 匡弘 北野 修二

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.14, no.1, pp.1-10, 2012 (Released:2012-06-29)

参考文献数

8

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無菌製剤製造に用いる陽圧型アイソレータにて,高生理活性物質を扱う場合,堅牢な封じ込めを行うハード面と同時に漏れを確実に捉えるソフト面(運用)が重要である。そこで,微粒子可視化装置を用い,陽圧型アイソレータ内でラクトースを噴霧した際にどのような飛散挙動を示すのか,また,実際に粉体をリークさせた際に周囲にどのように飛散して行くのかを確認した。これによりアイソレータの何処から漏れるリスクが高いのか評価することが出来,且つ実際の製造作業において,どの位置にどの程度サンプラーを設置しリークの有無を管理するが良いかをシステマチックなリスクマネージメントが可能となった。

著者

出口 統也

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.12, no.2, pp.70-77, 2010 (Released:2011-07-23)

参考文献数

11

著者

曲田 純二

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.11, no.2, pp.62-66, 2009 (Released:2010-10-02)

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.

著者

John W. Henderson Jr. William J. Long

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.2, pp.90-95, 2007 (Released:2008-12-25)

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窒素を含有する数種の心臓病治療薬について,ZORBAX Rapid Resolution (RR) 3.5 μm カラムと,Rapid resolution HT (RRHT) 1.8 μm カラムで,分離検討を行いました。分析メソッド開発の上で重要なポイントは分析時間,分離,感度ですが,RR カラム,RRHT カラムを使用してメソッド開発することで,これら 3 項目について最も満足できるメソッドを,素早く構築することができます。このアプリケーションノートでは,RR カラムと RRHT カラムを使い,分析時間,分離,感度の比較を行いました。更に,3 項目で最善の結果が得られた条件について,カラム温度を変更して分析することで,分離がシビアな成分の選択性の変更,分離の改善が行えるかを検討しました。

著者

Lothar Hartmann

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.8, no.2, pp.87-93, 2006 (Released:2008-02-01)

著者

新田 博夫 酒井 達

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.8, no.2, pp.106-117, 2006 (Released:2008-02-01)

参考文献数

7

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There are no guidelines on the application of media-fill run to eye drops. General Information chapter in Japanese Pharmacopoeia serves as a reference. However, this chapter is used as guidance chapter for sterile drug products for general purposes. This study was conducted to investigate whether media-fill runs are performed in eye-drops manufacturers, and to analysis questionnaire results of the runs. The questionnaire results showed that media-fill runs for eye drops are periodically carried out, and sterile manufacturing of eye drops meets high sterility requirements. Spot contamination rarely found in eye drops might be due to the worst operation in the manufacturing process such as inappropriate actions of workers. The most important point for manufacturers of eye drops are that how to reduce the incidence of these actions.

著者

竹澤 健一 片山 博仁 田中 広徳 田村 圭史郎 中村 みさ子 三宅 正一 室井 哲夫 百永 眞士 山岡 尚志 涌田 俊哉

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.8, no.1, pp.78-86, 2006 (Released:2007-05-10)

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In the revised “GMP Ministerial Ordinance on Drugs and Quasi-drugs” announced by MHLW in December 2004, “deviation control” was stipulated. In response to this, Manufacturer needs to prepare SOPs to control and handle deviations appropriately and any deviation has to be documented. When critical deviation is occurred, impact assessment on the quality has to be also performed. If the deviation may have quality impact, the deviation has to be notified to Licensed Marketing Approval Holder of the product. Therefore, manufacturing unit or quality unit in manufacturer is required to have sufficient knowledge and ability to execute root cause analysis, impact assessment and corrective action/preventative action (CAPA). In this article, by taking up the following three cases, how to handle deviations such as root cause analysis, impact assessment of quality and CAPA has been discussed. 1)  Deviation from the standard operating procedure in granulation process 2)  Deviation from the specification in pharmaceutical water 3)  Deviation from the humidity limit in stability chamber In each case, insufficient handling example is first introduced and then desirable way of thinking is shown along with appropriate example. Points to be considered are also discussed for a more appropriate handling.

著者

小嶋 茂雄

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.8, no.1, pp.26-38, 2006 (Released:2007-05-10)

参考文献数

8

著者

西畑 利明

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.8, no.1, pp.18-25, 2006 (Released:2007-05-10)

参考文献数

5

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遺伝子解析の著しい進歩,薬理ゲノミクスの治療および新薬開発への積極取り込みなど,科学技術の著しい進歩の中で,既存の医薬品の服用のあり方や新たに世の中に出てくる医薬品の機能は変化する兆しがあり,この変化は加速すると予想できる。この変化の向かっているところは,個々の患者に“最も適した医薬品は?”や“最も適した服用量は?”であり,本来の目標である患者本位の薬物治療を実施することにある。医薬品の服用のあり方や新たに世の中に出てくる医薬品の機能がどのように変化しようとも,製造販売承認を受けた医薬品を“製造・品質管理し,世の中に供給する使命”を遂行する上で,企業が遵守しなければならに絶対要件は“承認時の約束ごとである承認事項で決められた品質を医薬品が確保していること”である。この医薬品の保証の原点は企業の品質管理システムの内容と運用に依存するところが大きく,品質管理システムは科学技術・管理手法の進歩により変化することも認識する必要がある。医薬品の出荷基準に係わる品質保証を達成する手法として,品質管理システムの一つとしてのリスクマネジメント手法の導入・運用が重要となり,高度のリスクマネジメントを達成するための製造工程の Process Analytical Technology 手法の積極的活用が推奨されている。

著者

野村 弘実 小田 昌宏 長谷川 孝夫

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.7, no.1, pp.59-67, 2005 (Released:2006-07-07)

参考文献数

12

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Mustang® is composed of microporous modified hydrophilic polyethersulfone (PES) membranes, having uniform coating with quaternary amine (Q) group and sulfonic acid (S) group. Mustang® membrane chromatography shows high binding capacity even under the high flow rate, by its larger pore size, and convective surface structure. Therefore, Mustang® purification technology has merit as a simple, speedy, and scalable one, especially for removing of harmful factors and impurities in bioprocess purification, and also the purification of macromolecules like DNA, virus, plasmid, and proteins etc. Here it is introduced the examples of the viral/DNA removal, and adenovirus vector purification using Mustang® membrane chromatography. Safety and quality assurance can be added into manufacturing process of biological drugs by applying and strengthen this separation and purification technology.