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.2, no.1, pp.1-10, 2000 (Released:2006-08-01)

被引用文献数

1

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Harmonization of GMP has been intensively discussed in ICH, and the result is expected to emerge by the end of this year. Such kind of international harmonization is a pressing issue in the pharmaceutical industries, since the development of technology sometimes causes de-harmonization of regulations in various counties and area. Harmonization of regulations for pharmaceuticals have significance in deploying the worldwide research and development of new pharmaceuticals effectively. According to the harmonization of regulations for pharmaceuticals, activities of pharmaceutical industries have become rapidly global. In the area of quality control, “How to establish specifications” has been discussed in Q6A, and “Skip test,” “Process control” and “Parametric release” have reached to the agreement. These subjects were firstly discussed in the Joint Conference of Japan PDA and Association of Japan Pharm. Sci. in 1997 in Japan. “Parametric Release” has a close relation with validation, or it is a natural consequence of validation. It can be said, “Where there is Validation, there is Parametric Release. It should not be limited to “Sterility Test”, but should be applied to all of other specifications to determine the quality. As future issues of GMP in Japan, “Consultant” in ICH GMP Section 3(6), and FDA GMP Section 211-34 should be discussed in Japan, since there is no this section in Japan GMP. “Contract Manufacturing and Contract Laboratory” should also be discussed in future in Japan, since the concept of “Contract” is very much limited in the Japan GMP. “Complaint and Recall” should also be discussed from the view points of “Safety”, and results should be informed to the world with sound basis of safety. GMP inspection system should also be discussed in the world, after the agreement of written GMP. There seems to be significant differences in the written GMP, but there seems to be much differences in the implementation of GMP between men to men, area to area, country to country. Audit experiences of ISO 9000s show the importance of worldwide auditors' training. CTD (Common Technical Document), and various kinds of ISO Technical Requirements would have much influence to GMP. We have to watch these discussions. Under these circumstances, pharmaceutical industries in Japan are now expanding their activities from domestic to the world.

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

川村 邦夫 阿部 寛

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.134-140, 2002 (Released:2006-07-18)

参考文献数

7

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It is no doubt that media fill (simulation) test is the best method to evaluate aseptic processing. However, there are some problems concerning the acceptable criteria of “a contamination rate of less than 0.1% with 95% confidence limit”, which is specified in official compendia, such as JP,USP, EU GMP, WHO GMP, and ISO 13408 part 1 (General). In performing the media fill test, critical issues in performing media fills are the number of fills. Statistical validity of the observed contamination rate for the process has not been well explained hitherto. Problems associated with the “number” of criteria may not necessarily be treated with statistics, and personnel training and operation are sometimes major factors to cause contamination. However, dogma of “a contamination rate of less than 0.1% with 95% confidence limit” should be discussed further. Operation characteristic curves, which show the relationship between percent defectives and acceptance probability, clearly indicate that the more the number of fills, the higher the acceptable probability of contaminated units becomes in the range of contamination rate less than 0.1%. This means that the larger number of fills accept the worse average quality at the range of percent defectives less than 0.1%. According to a table of ISO 13408-1 (1998), which shows the relationship between the number of fills and the number of acceptable contaminated units, 10 positive units are accepted by 16970 fills' as the rate of contaminated units are less than 0.1% with a 95% confidence limit. However, the 95% confidential range of 4 positive units in 16970 fills is calculated to be 1/1970-6/16970. This means that zero (0) positive unit in 16970 fills, that is sterile prduct, is out-of control with a 95% confidence level. Even though the product meets the requirement of “less than 0.1% with a 95% confidence limit”, zero contamination unit in 16970 fills or asepsis must be very rare case. It means that sterile products become out-of-control according to the existing criteria. It is recommended that the dogmatic criteria such as less than 0.1% with 95% confidence limit should be revised. An example of a proposed new criteria is expressed as follows: “The result of media fill should show that the aseptic processing is consistently within the control limit (with a confidence limit of 95%) by using 3000 or more fills, and show the asepsis of the process or the validity of sterility of the product” in stead of “less than 0.1% with a 95% confidence limit.”

著者

川村 邦夫

出版者

東京大学

巻号頁・発行日

1967

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博士論文

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.1, no.1, pp.9-17, 1999 (Released:2006-08-04)

参考文献数

6

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There are various academic associations related to pharmaceutical sciences and technology, most of which are dealing with pharmaceuticals themselves. The focussed areas are to synthesize new chemical entities, to find new pharmacological or therapeutic effects, and to develop new dosage forms. Relatively few researches have been reported on the area of manufacturing process, although there have been various researches and studies have been performed, particularly since the time of introduction of the concept of validation. This would be attributed to the lack of appropriate JOURNAL which enables the active information exchange possible. The journal newly published by Japan PDA would encourage persons who are engaging manufacturing plant, development engineering, quality laboratory and also who are engaging in regulatory inspections. As some examples of subjects which are expected to be contributed to the Japan PDA Journal relating to the future concept of manufacturing plant and manufacturing control, several topics are introduced. In the future manufacturing plant, 1) environment controlled area would become limited area which is as small as necessary, which becomes possible by applying isolator system or barrier system. Even the classification of cleanliness would become different one in future, along with the study of air flow dynamics as well as the application of isolator system. 2) Application of Luciferin-Luciferase-Chemo-luminance, method of microbial control would make the current air borne microbes control method different one and to make more quick in getting result and feed back to the process. 3) Continuous and automatic monitoring of air borne particulate would make more strict control and more quick action possible. 4) Systematic analysis of various data obtained from the monitoring of water would make correlation among various specifications more clear. As the results, continuous automatic in-line monitoring of water system by using conductivity, TOC, pH, and particulate matter might be enough to assure the quality of water, after the accumulation of quality data. As an example, it might be revealed that TOC value of 25 ppb or less shows endotoxin of 0.25 EU/ml or less. UF membrane would be used more frequently, since it endures high pressure steam sterilization. 5) Hydrogen peroxide sterilization would be more frequently be used according to the development and application of gas monitoring system. Submission of such papers and active discussion would make the pharmaceutical industry active and regulatory agencies would be able to have sound scientific basis on each operation.