SUPPLEMENT II TO THE JAPANESE PHARMACOPOEIA SEVENTEENTH EDITION O‹cial from June 28, 2019 English Version THE MINISTRY OF HEALTH, LABOUR AND WELFARE Notice: This English Version of the Japanese Pharmacopoeia is published for the convenience 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. Printed in Japan The Ministry of Health, Labour and Welfare Ministerial Notification No. 49 Pursuant to Paragraph 1, Article 41 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Act No. 145, 1960), this notification stated that a part of the Japanese Pharmacopoeia was revised as follows*. NEMOTO Takumi The Minister of Health, Labour and Welfare June 28, 2019 A part of the Japanese Pharmacopoeia (Ministerial Notification No. 64, 2016) was revised as follows*. (The text referred to by the term ``as follows'' are omitted here. All of the revised Japanese Pharmacopoeia in accordance with this notification (hereinafter referred to as ``new Pharmacopoeia'' in Supplement 2) are made available for public exhibition at the Pharmaceutical Evaluation Division, Pharmaceutical Safety and Environmen- tal Health Bureau, Ministry of Health, Labour and Welfare, at each Regional Bureau of Health and Welfare, and at each Prefectural Office in Japan). Supplementary Provisions (Effective Date) Article 1 This Notification is applied from June 28, 2019. (Transitional measures) Article 2 In the case of drugs which are listed in the Japanese Pharmacopoeia (hereinafter referred to as ``previous Pharmacopoeia'') [limited to those listed in new Pharmacopoeia] and drugs which have been approved as of June 28, 2019 as prescribed under Paragraph 1, Article 14 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices [including drugs the Minister of Health, Labour and Welfare specifies (the Ministry of Health and Welfare Ministerial Notification No. 104, 1994) as of June 27, 2019 as those exempted from marketing approval pursuant to Paragraph 1, Article 14 of the same law (hereinafter referred to as ``drugs exempted from approval'')], the Stand- ards established in the previous Pharmacopoeia (limited to part of the Standards for the drugs concerned) may be accepted to conform to the Standards established in the new Pharmacopoeia before and on December 31, 2020. 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 June 28, 2019 as prescribed under the Paragraph 1, Article 14 of the same law (including those ex- empted from approval), they may be accepted as those being not listed in the new Pharmacopoeia before and on December 31, 2020. (Partial revision of Products Delivery Rules of National Institute of Infectious Dis- eases) Article 3 Omitted. *The term ``as follows'' here indicates the content of Supplement II to the Japanese Pharmacopoeia Seventeenth Edition from General Notice to Ultraviolet-visible Reference Spectra (pp. 2877 – 2991). CONTENTS Preface ...................................................... i General Information Supplement II to The Japanese Pharmacopoeia, G1 Physics and Chemistry Seventeenth Edition ......................... 2877–2991 Control of Elemental Impurities in General Notices ................................... 2877 Drug Products............................... 2993 General Rules for Preparations ............... 2879 G3 Biotechnological/Biological Products General Tests, Processes and Apparatus ... 2881 Host Cell Protein Assay ..................... 2997 2.01 Liquid Chromatography ................. 2881 Total Protein Assay........................... 3000 2.26 Raman Spectroscopy...................... 2882 G4 Microorganisms 2.46 Residual Solvents .......................... 2884 Media Fill Test (Process Simulation) ..... 3000 2.51 Conductivity Measurement.............. 2891 Microbiological Environmental Moni- 2.66 Elemental Impurities—Procedures .... 2893 toring Methods of Processing Areas 6.16 Rheological Measurements for Semi- for Sterile Pharmaceutical Products ... 3000 solid Preparations ......................... 2896 Parametric Release of Terminally Steri- 6.17 Insoluble Particulate Matter Test for lized Pharmaceutical Products .......... 3000 Therapeutic Protein Injections ......... 2900 G5 Crude Drugs 9.01 Reference Standards ...................... 2901 Purity Tests on Crude Drugs using 9.21 Standard Solutions for Volumetric Genetic Information ....................... 3000 Analysis ...................................... 2901 On the Scientiˆc Names of Crude Drugs 9.22 Standard Solutions ........................ 2901 listed in the JP .............................. 3005 9.41 Reagents, Test Solutions................. 2901 G8 Water 9.42 Solid Supports/Column Packings Quality Control of Water for Pharma- for Chromatography...................... 2908 ceutical Use .................................. 3006 G10 Others O‹cial Monographs ................................ 2909 Basic Concepts for Quality Assurance Crude Drugs and Related Drugs.............. 2973 of Drug Substances and Drug Prod- ucts ............................................. 3006 Infrared Reference Spectra ................ 2985–2987 Concept on Impurities in Chemically synthesized Drug Substances and Ultraviolet-visible Reference Spectra .... 2989–2991 Drug Products............................... 3008 Glossary for Quality by Design (QbD), Quality Risk Management (QRM) and Pharmaceutical Quality System (PQS) .......................................... 3010 International Harmonization Imple- mented in the Japanese Pharmaco- poeia Seventeenth Edition ................ 3014 Index.................................................... 3019 Index in Latin Name................................ 3039 Index in Japanese.................................... 3041 PREFACE The 17th Edition of the Japanese Pharmacopoeia It was also agreed that JP articles should cover (JP) was promulgated by Ministerial Notification drugs, which are important from the viewpoint of No.64 of the Ministry of Health, Labour and Welfare health care and medical treatment, clinical perform- (MHLW) on March 7, 2016. ance or merits and frequency of use, as soon as possi- In July 2016, the Committee on JP established the ble after they reach the market. basic principles for the preparation of the JP 18th Edi- The target date for the publication of JP 18th Edi- tion, setting out the roles and characteristics of the JP, tion (the Japanese edition) was set as April 2021. the definite measures for the revision, and the date of JP drafts are discussed in the following committees the revision. that were established in the Pharmaceuticals and Med- It was agreed that the JP should provide an official ical Devices Agency: Expert Committee; Sub-expert standard, being required to assure the quality of medi- Committee; Sub-committee on Manufacturing Proc- cines in Japan in response to the progress of science ess-related Matters; Committee on Chemicals; Com- and technology and medical demands at the time. It mittee on Antibiotics; Committee on Biologicals; should define the standards for specifications, as well Committee on Crude Drugs; Committee on Phar- as the methods of testing to assure overall quality of maceutical Excipients; Committee on Physico-Chemi- all drugs in principle, and it should have a role in cal Methods; Committee on Drug Formulation; Com- clarifying the criteria for quality assurance of drugs mittee on Physical Methods; Committee on Biological that are recognized to be essential for public health Methods; Committee on Nomenclature for Phar- and medical treatment. maceuticals; Committee on International Harmoniza- The JP has been prepared with the aid of the tion; and Committee on Reference Standards. Fur- knowledge and experience of many professionals in thermore, working groups are established under the the pharmaceutical field. Therefore, the JP should Expert Committee, Committee on Pharmaceutical Ex- have the characteristics of an official standard, which cipients, Committee on Physico-Chemical Methods might be widely used by all parties concerned, and it and Committee on Drug Formulation. should play an appropriate role of providing informa- The committees initiated deliberations on several re- tion and understanding about the quality of drugs to visions. the public. Moreover, as a pharmaceutical quality Draft revisions covering subjects in General No- standard, it should contribute promoting and main- tices, General Rules for Preparations, General Tests, taining of advancedness as well as international con- Monographs, Ultraviolet-visible Reference Spectra sistency and harmonization of technical requirements and Infrared Reference Spectra for which discussions in the international community. were finished between April 2017 and November 2018, At the Committee, the five basic principles of JP, were prepared for a supplement to the JP 17. which we refer to as the ``five pillars'', were estab- Numbers of discussions in the committees to pre- lished as follows: 1) Including all drugs which are im- pare the supplement drafts were as follows: Expert portant from the viewpoint of health care and medical Committee (11, including a working group); Sub-com- treatment; 2) Making qualitative improvement by in- mittee on Manufacturing Process-related Matters (6), troducing the latest science and technology;