Requirements in Japan

In Japan, the structural analysis for RPVIs is described in METI notification 501, [3.5] and JSME Code on Code for Design and Construction for Nuclear Power Plants, JSME S NCl-2001 [3.6], which are based on ASME Boiler and Pressure Vessel Code, Section HI.. 

Some internationally harmonized guidelines regarding specifications and tests, impurities and validation of analytical methods have particular relevance to the development of chiral drugs and are discussed below. In addition, the impact of work on the common technical document is considered. 

Guidance on specifications is divided into universal tests/criteria which are considered generally applicable to all new substances/products and specific tests/criteria which may need to be addressed on a case-by-case basis when they have an impact on the quality for batch control. Tests are expected to follow the ICH guideline on analytical validation (Section 13.5.4). Identification of the drug substance is included in the universal category, and such a test must be able discriminate between compounds of closely related structure which are likely to be present. It is acknowledged here that optically active substances may need specific identification testing or performance of a chiral assay in addition to this requirement. 

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Yakuji Nippo, Ltd. (1991). Drug Registration Requirements in Japan. Yakuji Nippo, Ltd., Tokyo, Japan. 

Relationships are looser in some countries. The health authority of Canada claims that the Canadian GMP guidelines of 2002 [16] have been revised in line with the PIC and the WHO guides as well as the GMP guide on APIs produced by ICH. (See below.) The Japanese Ministry of Health, Labor, and Welfare (MHLW) explains that ordinance no. 3 as the legal base for GMP requirements in Japan [17] has been drawn up taking into account both the relevant paragraphs of the U.S. CFR, parts 210 and 211, as well as the WHO guide. 

Preliminary studies over 3 months in groups of 10 animals each are an essential requirement in Japan. Since adequate dose levels for such a long-term study are difficult to define beforehand, short dose-finding trials may be be useful for other countries, too. 

Another problem is related to the expanding use of alternative fuels, such as natural gas. For example, natural gas fueled diesel exhausts often are too cold for currently available oxidation catalysts that need 450°C for methane destmction required in Japan and Europe. 

Epidemiologic studies in Japan indicate an increased risk of stomach cancer owing to consumption of broiled fish and meats (116). In the United States, stomach cancer incidence has steadily declined since the 1940s, whereas consumption of broiled food has increased (108). In addition, the average human intake of PAHs is only 0.002 of that required to produce cancer in half of animals fed. Test results are often contradictory (117) and many components of food, such as vitamin A, unsaturated fatty acids, thiols, nitrites, and even saUva itself, tend to inhibit the mutagenic activity of PAHs (118—120). Therefore, the significance of PAHs in the human diet remains unknown (121,109). 

A newer juice concentration process, requiring minimal heat treatment, has been appHed commercially in Japan to citms juice concentration. The pulp is separated from the juice by ultrafiltration and pasteurized. The clarified juice containing the volatile flavorings is concentrated at 10°C by reverse osmosis (qv) and the concentrate and pulp are recombined to produce a 42—51 °Brix citms juice concentrate. The flavor of this concentrate has been judged superior to that of commercially available concentrate, and close to that of fresh juice (11). 

Plant investment and maintenance costs are relatively high for a new iodine plant in the United States or in Japan because of the deep weUs required for brine production and disposal as weU as the corrosive nature of the plant streams. The principal materials cost is for chlorine and for sulfur dioxide, although in the United States the additives used for the brines, such as scale inhibitors and bactericides, also have a considerable influence on costs. 

Polyuretha.ne, A type of spunbonded stmcture has been commercialized in Japan based on thermoplastic polyurethanes (15). This represents the first commercial production of such fabrics, although spunbonded urethane fabrics have been previously discussed (16). The elastomeric properties claimed are unique for spunbonded products and appear to be weU suited for use in apparel and other appHcations requiring stretch and recovery. Polyurethanes are also candidates for processing by the meltblown process. 

The demand for electrode binder pitch has grown as aluminium output has expanded and the requirement for aluminium smelting is now between 1.5 and 2 x 10 t /yr. In Japan pitch is used for mixing with coal for carbonization in coke ovens to make metallurgical coke. 

Mutation. For industrial appHcations, mutations are induced by x-rays, uv irradiation or chemicals (iiitrosoguanidine, EMS, MMS, etc). Mutant selections based on amino acid or nucleotide base analogue resistance or treatment with Nystatin or 2-deoxyglucose to select auxotrophs or temperature-sensitive mutations are easily carried out. Examples of useful mutants are strains of Candida membranefaciens, which produce L-threonine Hansenu/a anomala, which produces tryptophan or strains of Candida lipolytica that produce citric acid. An auxotrophic mutant of S. cerevisiae that requires leucine for growth has been produced for use in wine fermentations (see also Wine). This yeast produces only minimal quantities of isoamyl alcohol, a fusel oil fraction derived from leucine by the Ehrlich reaction (10,11). A mutant strain of bakers yeast with cold-sensitive metaboHsm shows increased stabiUty and has been marketed in Japan for use in doughs stored in the refrigerator (12). 

Japan. In Japan, registration of dmgs for aquatic species requires the same data as those required for dmgs on other animals. The Ministry of Agriculture, Eorests, and Eisheries and the Ministry of Welfare control the use of chemicals in aquaculture in Japan (17). The preclinical data requirements include product chemistry, toxicity (acute, subacute, special) using rats and mice, safety to target animals, and metaboHsm. The requirements for clinical data include avadabiHty and residues. As of July 1990, more chemicals were registered for aquacultural use in Japan than in any other country (Table 4). 

The most active -butyraldehyde derivatives are expected to be PVB, as more regions require automotive safety glass, and trimethylolpropane. Overall annual growth in -butyraldehyde through 1993 is expected to be 0.9% in the United States and 1.2% in Japan. No growth in -butyraldehyde consumption is expected in Western Europe through 1993. 

Now that it is possible to establish test facilities in a laboratory to simulate the time history of an earthquake seismic tests are conducted by creating the ground movements in the test object. Other methods, such as by analysis or by combined analysis and testing, are also available. Refer to IEEE 344 and lEC 60980 for more details. For this purpose a shake table, able to simulate the required seismic conditions (RRS) is developed on which the test object is mounted and its performance observed under the required shock conditions. Since it is not easy to create such conditions in a laboratory, there are only a few of these facilities available. The better equipped laboratories are in Japan, the USA, the UK, Greece, Germany, India and China. In India the Earthquake Engineering Department (EQD) of the University of Roorkee (UoR) is equipped with these facilities. 

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