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.

View full abstract

[in Japanese]

View full abstract

The pharmaceutical quality and related matters by outsourcing in pharmaceutical development are described from a viewpoint of contract giver based on the recent development trend of Japanese pharmaceutical companies. The quality risk management by a contract giver should be conducted as the product lifecycle for outsourcing in pharmaceutical development. Although speed and technology are primarily requisites for the development, the quality agreement for confidentiality and patent rights should be also required. The global GMP should be conformed for the manufacturing of investigational medicinal products. Change control and technology transfer in the development process should be justified the consistency of products. The NDA by a contract giver should be consistent with information through the development process and compiled as a result.

View full abstract

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.

View full abstract

 “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.

View full abstract

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.

View full abstract