SUPPLEMENT II TO THE JAPANESE PHARMACOPOEIA FIFTEENTH EDITION Official From October 1, 2009 English Version THE MINISTRY OF HEALTH, LABOUR AND WELFARE Notice: This English Version of the Japanese Pharmacopoeia is published for the conven- ience of users unfamiliar with the Japanese language. When and if any discrepancy arises between the Japanese original and its English translation, the former is authentic. The Ministry of Health, Labour and Welfare Ministerial Notification No. 425 Pursuant to Paragraph 1, Article 41 of the Pharmaceutical Affairs Law (Law No. 145, 1960), we hereby revise a part of the Japanese Pharmacopoeia (Ministerial Notification No. 285, 2006) as follows*, and the revised Japanese Pharmacopoeia shall come into ef- fect on October 1, 2009. However, in the case of drugs which are listed in the Japanese Pharmacopoeia (hereinafter referred to as “previous Pharmacopoeia”) [limited to those listed in the Japanese Pharmacopoeia whose standards are changed in accordance with this notification (hereinafter referred to as “new Pharmacopoeia”)] and drugs which have been approved as of October 1, 2009 as prescribed under Paragraph 1, Article 14 of the same law [including drugs the Minister of Health, Labour and Welfare specifies (the Ministry of Health and Welfare Ministerial Notification No. 104, 1994) as those ex- empted from marketing approval pursuant to Paragraph 1, Article 14 of the Pharmaceu- tical Affairs Law (hereinafter referred to as “drugs exempted from approval”)], the Name and Standards established in the previous Pharmacopoeia (limited to part of the Name and Standards for the drugs concerned) may be accepted to conform to the Name and Standards established in the new Pharmacopoeia before and on March 31, 2011. In the case of drugs which are listed in the new Pharmacopoeia (excluding those listed in the previous Pharmacopoeia) and drugs which have been approved as of October 1, 2009 as prescribed under Paragraph 1, Article 14 of the same law (including those exempted from approval), they may be accepted as those being not listed in the new Pharmacopoeia be- fore and on March 31, 2011. Akira Nagatsuma The Minister of Health, Labour and Welfare September 30, 2009 (The text referred to by the term “as follows” are omitted here. All of them are made available for public exhibition at the Evaluation and Licensing Division, Pharmaceuti- cal and Food Safety Bureau, Ministry of Health, Labour and Welfare, at each Regional Bureau of Health and Welfare, and at each Prefectural Office in Japan). *The term “as follows” here indicates the contents of Supplement II to the Japanese Pharmacopoeia Fifteenth Edition from General Notice to Ultraviolet-visible Reference Spectra (pp. 2041‐2276). CONTENTS Preface ........................................................................ i Official Monographs ...........................................2073 Supplement II to The Japanese Pharmacopoeia, Crude Drugs ....................................................2219 Fifteenth Edition........................................ 2041-2276 General Rules for Crude Drugs ........................ 2041 Infrared Reference Spectra ...................... 2241-2260 General Tests, Process and Apparatus .............. 2043 1.07 Heavy Metals Limit Test......................... 2043 Ultraviolet-visible Reference Spectra ...... 2261-2276 1.08 Nitrogen Determination (Semimicro- Kjeldahl Method).................................... 2043 General Information ...........................................2277 1.09 Qualitative Tests ..................................... 2044 8. International Harmonization Implemented in the 2.01 Liquid Chromatography.......................... 2045 Japanese Pharmacopoeia Fifteenth 2.04 Amino Acid Analysis of Proteins............ 2046 Edition........................................................2279 3.01 Determination of Bulk and Tapped 14. Mycoplasma Testing for Cell Substrates used for Densities ................................................. 2047 the Production of Biotechnological/ 3.02 Specific Surface Area by Gas Adsorp- Biological Products....................................2281 tion.......................................................... 2049 32. Near Infrared Spectrometry .......................2284 3.03 Powder Particle Density Determination.. 2052 34. System Suitability......................................2290 3.04 Particle Size Determination .................... 2053 35. Powder Fineness........................................2291 7.02 Test Methods for Plastic Containers ....... 2057 9.01 Reference Standards ............................... 2057 Index .....................................................................2293 9.41 Reagents, Test Solutions......................... 2058 Index in Latin Name............................................2309 9.42 Solid Supports/Column Packings for Index in Japanese ................................................2311 Chromatography ..................................... 2072 PREFACE The 15th Edition of the Japanese Pharmacopoeia and medical treatment, clinical results and frequency (JP) was promulgated by Ministerial Notification No. of use, as soon as possible after they reach the market. 285 of the Ministry of Health, Labour and Welfare The target date for the publication of JP 16th Edition (MHLW) on March 31, 2006. (the Japanese edition) was set as April 2011. In July 2006, the Committee on JP established the JP Expert Committees are organized with the fol- basic principles for the preparation of the JP 16th Edi- lowing panels: Panel on the Principles of Revisions; tion, setting out the roles and characteristics of the JP, Sub-committee on the Principles of Revisions; Panel the definite measures for the revision, and the date of on Medicinal Chemicals; Panel on Antibiotics; Panel the revision. on Biologicals; Panel on Crude Drugs; Panel on Phar- At the above Committee, the five basic principles of maceutical Excipients; Panel on Physico-Chemical JP, which we refer to as the “five pillars” were estab- Methods; Panel on Preparations; Panel on Physical lished as follows: 1) Including all drugs which are im- Methods; Panel on Biological Tests; Panel on Nomen- portant from the viewpoint of health care and medical clature; Panel on International Harmonization; Panel treatment; 2) Making qualitative improvement by in- on Pharmaceutical Water; and Panel on Reference troducing the latest science and technology; 3) Pro- Standards. Furthermore, working groups are estab- moting internationalization; 4) Making prompt partial lished under the Panel on Physico-Chemical Methods, revision as necessary and facilitating smooth adminis- Panel on Preparations and Panel on Biological Tests to trative operation; and 5) Ensuring transparency re- expedite discussion of revision drafts of Monographs. garding the revision, and disseminating the JP to the In the Committee on JP, Takao Hayakawa took the public. It was agreed that the Committee on JP should role of chairman from July 2003 to September 2009. make efforts, on the basis of these principles, to ensure In addition to the regular revision every five years in that the JP is used more effectively in the fields of line with the basic principles for the preparation of the health care and medical treatment by taking appropri- JP it was agreed that partial revision should be done as ate measurements, including getting the understanding necessary to take account of recent progress of science and cooperation of other parties concerned. and in the interests of international harmonization. It was agreed that the JP should provide an official In accordance with the above principles, the panels standard, being required to assure the quality of medi- initiated deliberations on selection of articles, and on cines in Japan in response to the progress of science revisions for General Notices, General Rules for Crude and technology and medical demands at the time. It Drugs, General Rules for Preparations, General Tests, should define the standards for specifications, as well Monographs and so on. as the methods of testing to assure overall quality of all Draft revisions covering subjects in General Rules drugs in principle, and it should have a role in clarify- for Crude Drugs, General Tests and Monographs, for ing the criteria for quality assurance of drugs that are which discussions were finished between April 2007 recognized to be essential for public health and medi- and March 2009, were prepared for a supplement to cal treatment. the JP 15. They were examined by the Committee on The JP has been prepared with the aid of the knowl- JP in April 2009, followed by the Pharmaceutical Af- edge and experience of many professionals in the fairs and Food Sanitation Council (PAFSC) in June pharmaceutical field. Therefore, the JP should have the 2009, and then submitted to the Minister of MHLW. characteristics of an official standard, which might be Numbers of discussions in the panels to prepare the widely used by all parties concerned. It should provide supplement drafts were as follows: Panel on Principles information and understanding about the quality of of Revisions (3); Panel on Medicinal Chemicals (23); drugs to the public, and it should be conducive to Panel on Antibiotics (8); Panel on Biologicals (8); smooth and effective regulatory control of the quality Panel on Crude Drugs (21); Panel on Pharmaceutical of drugs, as well as promoting and maintaining inter- Excipients (10): Panel on Physico-Chemical Methods national consistency and harmonization