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.

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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。

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　医薬品の開発段階における委受託については，委託者の開発戦略と品質ポリシーに基づいて品質リスクマネジメントによる評価を行い，製品ライフサイクルの一環として検討するべきである。委託に際しては，単にスピードや技術に注力するだけでなく，コンフィデンシャリティやパテントについての取り決めも考慮する必要がある。治験薬の製造にあたっては 3 極対応として治験薬 GMP を遵守し，開発過程の情報については変更管理を行い，技術移管時に製品として品質の一貫性を確保する。委託者による承認申請書は，これら全ての情報の最終的な集約でなくてはならない。

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Recent information on GMP has been described, which includes the followings: product recalls in 2006 in Japan, memorandum of MHLW with EU on MRA, brief report on the revised medium-ranged plan of PDMA, brief reports on the GMP discussion meeting in Yamaguchi Prefecture, on the discussion meeting on biotechnology in Ohita Prefecture, and on the discussion meeting sponsored by the Pharmaceutical Technologists Association in Saga Prefecture. Several guidelines issued by EMEA were exposited. Product recalls in U.S. in 2006, which have been posted on FDA web-site were analyzed with respect to their recall classification and reasons. The report on India moving its centralization of regulations on medicines and medical devices was made shortly.

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 “Japanese Guideline for Industry on sterile drug products produced by aseptic processing” was published in July 2006 by MHLW. The chapter of “PEST CONTROL OF PROCESSING AREAS” has newly been installed in the guideline.
 Generally, it tends to have been thought that there are no insects or arthropods in APAs wherein a highly clean level is kept. However, many actual data obtained has clearly shown that there were very few facilities with no insects or arthropods but a specific fauna found in clean areas, as a result of our investigation. The author and coworkers have investigated insects and arthropods in Grade B areas for 11 years. The limited kinds of species of insects and arthropods detected in some clean rooms are so statistically indicated that 98.5% of the insects and arthropods captured by sticky traps are clearly found to be the species emerging from inside the facility. Most of them (94.7%) are fungivorous, wingless and other tiny species. These pests may be spreading some microbes or spores on their bodies. And if any fungivorous pest is found in a clean room, there is an unfavorable risk of infestation with the fungus in and/or outside the clean room. Therefore, a special notice is described hereupon “Identification of these pests is also important to maintain cleanliness, because such insects are available as an indicator of overall biological contamination” in the above-mentioned chapter.
 All the other detailed back data relating to this report will be further supplementing the description in the chapter, though all of them was not provided herein. The data based on the results of our investigation in Grade B however, shows the insect fauna, population density, spatial distribution patterns, etc. Moreover, some key points of contamination due to such insects have also been discussed about their food chains, relationship between fungivorous insects and the fungi, and cause of their occurrence.

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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.

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