THE JAPANESE PHARMACOPOEIA SEVENTEENTH EDITION JP-17
The Japanese Pharmacopoeia (JP) is an official document that defines the specifications, criteria and standard test methods necessary to properly assure the quality of medicines in Japan.
Paragraph 2, Article 41 of the Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices stipulates that full-fledged JP revisions shall be presented at least every 10 years. Since the JP 9th edition, full-fledged revisions have been made every 5 years. In addition to the full-fledged revisions, a supplement has been promulgated twice in every 5 years since the JP 12th edition as well as partial revisions have been made as necessary to take account of recent progress of science and in the interests of international harmonization.
The 16th Edition of the JP was promulgated by Ministerial Notification No. 65 of the Ministry of Health, Labour and Welfare (MHLW) on March 24, 2011.
In July 2011, the Committee on JP established the basic principles for the preparation of the JP 17th Edi-tion, setting out the roles and characteristics of the JP, the definite measures for the revision, and the date of the revision.
At the Committee, the five basic principles of JP, whichwerefer to as the``fivepillars'',wereestab-lished as follows: 1) Including all drugs which are im-portant from the viewpoint of health care and medical treatment; 2) Making qualitative improvement by introducing the latest science and technology; 3) Promoting internationalization; 4) Making prompt partial revision as necessary and facilitating smooth administrative operation; and 5) Ensuring transparen-cy regarding the revision, and disseminating the JP to the public. It was agreed that the Committee on JP should make efforts, on the basis of these principles, to ensure that the JP is used more effectively in the fields of health care and medical treatment by taking appropriate measurements, including getting the understanding and cooperation of other parties con-cerned.
It was agreed that the JP should provide an official standard, being required to assure the quality of medi-cines in Japan in response to the progress of science and technology and medical demands at the time. It should define the standards for specifications, as well as the methods of testing to assure overall quality of all drugs in principle, and it should have a role in clarifying the criteria for quality assurance of drugs that are recognized to be essential for public healthand medical treatment. The JP has been prepared with the aid of the knowledge and experience of many professionals in the pharmaceutical field. Therefore, the JP should have the characteristics of an official standard, which might be widely used by all parties concerned, and it should play an appropriate role of providing information and understanding about the quality of drugs to the public. Moreover, as a phar-maceutical quality standard, it should contribute promoting and maintaining of advancedness as well as international consistency and harmonization of techni-cal requirements in the international community. It was also agreed that JP articles should cover drugs, which are important from the viewpoint of health care and medical treatment, clinical performance or merits and frequency of use, as soon as possible after they reach the market.
The target date for the publication of JP 17th Edi-tion (the Japanese edition) was set as April 2016.
JP Expert Committees were originally organized with the following committees: Expert Committee; Sub-expert Committee; Committee on Chemicals; Committee on Antibiotics; Committee on Biologicals; Committee on Crude Drugs; Committee on Pharma-ceutical Excipients; Committee on Physico-Chemical Methods; Committee on Drug Formulation; Com-mittee on Physical Methods; Committee on Biological Methods; Committee on Nomenclature for Pharma-ceuticals; Committee on International Harmonization; Committee on Pharmaceutical Water and Committee on JP Reference Standards. Furthermore, working groups were established under the Committee on Physico-Chemical Methods; Committee on Drug For-mulation and Committee on Biological Methods to expedite discussion on revision drafts. Later, the Ex-pert Committees were reorganized in order to solve technical issues with preparation of JP drafts; the Sub-committee on Manufacturing Process-related Matters was newly established and the Committee on JP Refer-ence Standards was re-formed and renamed Com-mittee on Reference Standards. Moreover, working groups were established under the Committee on Phar-maceutical Excipients and Committee on International Harmonization.
In the Committee on JP, Mitsuru Hashida took the role of chairman from January 2011 to March 2016.
In accordance with the above principles, the com-mittees initiated deliberations on selection of articles and on revisions for General Notices, General Rules for Crude Drugs, General Rules for Preparations,General Tests, Monographs and so on.
In order to ensure distribution of drugs in the area hit by the 2011 off the Pacific coast of Tohoku Ear-thquake on March 11, 2011, for those drugs that were distributed by the distributors in the same quake-hit area, the expiry date of interim measure of the Supple-ment II to the JP 15th Edition under the Ministerial Notification No. 425 of the MHLW dated September 30, 2009 was extended to June 30, 2013 and that of the Partial Revision of the JP 15th Edition under the Ministerial Notification No. 322 of the MHLW dated July 30, 2010 was extended to January 31, 2012, which was promulgated as the partial revision of the pream-ble of the Ministerial Notification of the JP 16th Edi-tion by Ministerial Notification No. 96 of the MHLW on March 31, 2011, and became effective.
Draft revisions covering subjects in General Notices, General Rules for Crude Drugs, General Rules for Preparations, General Tests and Monographs, for which discussions were finished between April 2010 and March 2012, were prepared for a supplement to the JP 16. They were examined by the Committee on JP in May 2012, followed by the Pharmaceutical Af-fairs and Food Sanitation Council (PAFSC) in June 2012, and then submitted to the Minister of Health, Labour and Welfare.
The supplement was named ``Supplement I to the JP 16th Edition'', promulgated on September 27, 2012 by Ministerial Notification No. 519 of MHLW, and became effective on October 1, 2012.
Numbers of discussions in the committees to pre-pare the supplement drafts were as follows: Expert Committee (8); Sub-expert Committee (4), Committee on Chemicals (22), Committee on Antibiotics (5); Committee on Biologicals (9); Committee on Crude Drugs (21); Committee on Pharmaceutical Excipients (12); Committee on Physico-Chemical Methods (14); Committee on Drug Formulation (19); Committee on Physical Methods (7); Committee on Biological Methods (13); Committee on Nomenclature for Phar-maceuticals (7); Committee on International Harmoni-zation (8); and Committee on Pharmaceutical Water (7).
It should be noted that in the preparation of the drafts for the supplement, generous cooperation was given by the Pharmaceutical Technology Committee of the Osaka Pharmaceutical Manufacturers Associa-tion, the Pharmacopeia and CMC Committee of the Pharmaceutical Manufacturers' Association of Tokyo, the Tokyo Crude Drugs Association, the Inter-national Pharmaceutical Excipients Council Japan, the Japan Kampo Medicines Manufacturers Associa-tion, the Japan Flavor and Fragrance Materials As-sociation, the Japan Medicinal Plant Federation, the Japan Pharmaceutical Manufacturers Association, the Parenteral Drug Association Japan Chapter, theJP XVII
Japan Reagent Association, the Japan Oilseed Proces-sors Association, the Home Medicine Association of Japan, and the Association of Membrane Separation Technology of Japan.
In consequence of this revision, the JP 16th Edition carries 1837 articles, owing to the addition of 77 arti-cles and the deletion of 4 articles.
Draft revisions covering subjects, the revision of the General Tests and the revision of the specification of monograph Gelatin connected with the harmonization among the three pharmacopoeias, JP, EP and USP were examined by the Committee on JP in February 2013, followed by PAFSC in April 2013, and then sub-mitted to the Minister of Health, Labour and Welfare.
This revision was promulgated on May 31, 2013 by Ministerial Notification No. 190 of MHLW, and became effective.
Draft revisions covering subjects in General Notices, General Rules for Crude Drugs, General Rules for Preparations, General Tests and Monographs, for which discussions were finished between April 2012 and September 2013, were prepared for a supplement to the JP 16. They were examined by the Committee on JP in October 2013, followed by the PAFSC in De-cember 2013, and then submitted to the Minister of Health, Labour and Welfare.
The supplement was named ``Supplement II to the JP 16th Edition'' and promulgated on February 28, 2014 by Ministerial Notification No. 47 of MHLW, and became effective.
Numbers of discussions in the committees to pre-pare the supplement drafts were as follows: Expert Committee (5); Sub-committee on Manufacturing Process-related Matters (6); Committee on Chemicals (16); Committee on Antibiotics (3); Committee on Biologicals (8); Committee on Crude Drugs (16); Com-mittee on Pharmaceutical Excipients (12); Committee on Physico-Chemical Methods (9); Committee on Drug Formulation (14); Committee on Biological Methods (13); Committee on Nomenclature for Phar-maceuticals (4); Committee on International Harmoni-zation (10); and Committee on Reference Standards (1).
It should be noted that in the preparation of the drafts for the supplement, generous cooperation was given by the Pharmaceutical Technology Committee of the Osaka Pharmaceutical Manufacturers Associa-tion, the Pharmacopeia and CMC Committee of the Pharmaceutical Manufacturers' Association of Tokyo, the Tokyo Crude Drugs Association, the Inter-national Pharmaceutical Excipients Council Japan, the Japan Kampo Medicines Manufacturers Associa-tion, the Japan Flavor and Fragrance Materials As-sociation, the Japan Medicinal Plant Federation, the Japan Pharmaceutical Manufacturers Association, the Federation of Pharmaceutical Manufacturers' Associ-JP XVII
ation of Japan, the Parenteral Drug Association Japan Chapter, the Japan Reagent Association, the Japan Oilseed Processors Association, the Home Medicine Association of Japan, the Association of Membrane Separation Technology of Japan, the External Phar-maceutical Association, the Japan Alcohol Associa-tion and the Pharmacopoeial Drug Society.
In consequence of this revision, the JP 16th Edition carries 1896 articles, owing to the addition of 60 arti-cles and the deletion of 1 article.
In accordance with the change of the title from Pharmaceutical Affairs Law (Act No. 145 of 1960) to Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices by the Law for Partial Revision of the Phar-maceutical Affairs Law (Act No. 84 of 2013), the par-tial revision to change from ``Pharmaceutical Affairs Law'' to ``Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices'' in JP General Notices was promul-gated on November 21, 2014 by Ministerial Notifica-tion No. 439 of MHLW, and became effective.
Draft revisions covering subjects in General Notices, General Rules for Crude Drugs, General Rules for Preparations, General Tests and Monographs, for which discussions were finished between October 2013 and July 2015, were prepared for a supplement to the JP 17. They were examined by the Committee on JP in August 2015, followed by the PAFSC in September 2015, and then submitted to the Minister of Health, Labour and Welfare.
Numbers of discussions in the committees to pre-pare the supplement drafts were as follows: Expert Committee (7); Sub-committee on Manufacturing Process-related Matters (12); Committee on Chemicals (22); Committee on Antibiotics (8); Committee on Biologicals (11); Committee on Crude Drugs (21); Committee on Pharmaceutical Excipients (10, includ-ing working group); Committee on Physico-Chemical Methods (9, including working group); Committee on Drug Formulation (23, including working group); Committee on Physical Methods (7); Committee on Biological Methods (12, including working group); Committee on Nomenclature for Pharmaceuticals (6); Committee on International Harmonization (10, in-cluding working group); and Committee on Reference Standards (8).
It should be noted that in the preparation of the drafts for the supplement, generous cooperation was given by the Pharmaceutical Technology Committee of the Osaka Pharmaceutical Manufacturers Associa-tion, the Pharmacopeia and CMC Committee of the Pharmaceutical Manufacturers' Association of Tokyo, the Tokyo Crude Drugs Association, the Inter-national Pharmaceutical Excipients Council Japan, the Home Medicine Association of Japan, the JapanKampo Medicines Manufacturers Association, the Japan Flavor and Fragrance Materials Association, the Japan Medicinal Plant Federation, the Japan Pharmaceutical Manufacturers Association, the Federation of Pharmaceutical Manufacturers' Associ-ation of Japan, the Parenteral Drug Association Japan Chapter, the Japan Reagent Association, the Japan Oilseed Processors Association, the Association of Membrane Separation Technology of Japan, the Ex-ternal Pharmaceutical Association, the Japan Alcohol Association, and the Pharmacopoeial Drug Society.
In consequence of this revision, the JP 17th Edition carries 1962 articles, owing to the addition of 76 arti-cles and the deletion of 10 articles.
The principles of description and the salient points of the revision in this volume are as follows:
1. The JP 17th Edition comprises the following items, in order: Notification of MHLW; Contents; Preface; General Notices; General Rules for Crude Drugs; General Rules for Preparations; General Tests, Processes and Apparatus; Official Monographs; then followed by Infrared Reference Spectra and Ultravio-let-visible Reference Spectra; General Information; Table of Standard Atomic Weights as an appendix; and a Cumulative Index.
2. The articles in Official Monographs, Infrared Reference Spectra and Ultraviolet-visible Reference Spectra are respectively placed in alphabetical order in principle.3. The following items in each monograph are putin the order shown below, except that unnecessary items are omitted depending on the nature of the drug:(1) English title
(2) Commonly used name(s)
(3) Latin title (only for crude drugs)
(4) Title in Japanese
(5) Structural formula or empirical formula
(6) Molecular formula and molecular mass
(7) Chemical name
(8) Chemical Abstracts Service (CAS) Registry Number
(9) Origin
(10) Limits of the content of the ingredient(s) and/or the unit of potency
(11) Labeling requirements
(12) Method of preparation
(13) Manufacturing requirement
(14) Description
(15) Identification tests
(16) Specific physical and/or chemical values
(17) Purity tests
(18) Potential adulteration
(19) Loss on drying or Ignition, or Water
(20) Residue on ignition, Total ash or Acid-insoluble ash(21) Tests being required for pharmaceutical prepa-rations
(22) Other special tests
(23) Assay
(24) Containers and storage
(25) Shelf life
(26) Others
4. In each monograph, the following physical andchemical values representing the properties and quality of the drug are given in the order indicated below, ex-cept that unnecessary items are omitted depending on thenatureofdrug:(1) Alcohol number
(2) Absorbance
(3) Congealing point
(4) Refractive index
(5) Osmolar ratio
(6) Optical rotation
(7) Constituent amino acids
(8) Viscosity
(9) pH
(10) Content ratio of the active ingredients
(11) Specific gravity
(12) Boiling point
(13) Melting point
(14) Acid value
(15) Saponification value
(16) Ester value
(17) Hydroxyl value
(18) Iodine value
5. Identification tests comprise the followingitems, which are generally put in the order given below:(1) Coloration reactions
(2) Precipitation reactions
(3) Decomposition reactions
(4) Derivatives
(5) Infrared and/or ultraviolet-visible absorption(6) Nuclear magnetic resonance spectrometry
(7) Chromatography
(8) Special reactions
(9) Cations
(10) Anions
6. Purity tests comprise the following items, which(8) Sulfate
(9) Sulfite
(10) Nitrate
(11) Nitrite
(12) Carbonate
(13) Bromide
(14) Iodide
(15) Soluble halide
(16) Thiocyanate
(17) Selenium
(18) Cationic salts
(19) Ammonium
(20) Heavy metals
(21) Iron
(22) Manganese
(23) Chromium
(24) Bismuth
(25) Tin
(26) Aluminum
(27) Zinc
(28) Cadmium
(29) Mercury
(30) Copper
(31) Lead
(32) Silver
(33) Alkaline earth metals
(34) Arsenic
(35) Free phosphoric acid
(36) Foreign matters
(37) Related substances
(38) Isomer
(39) Optical isomer
(40) Multimers
(41) Residual solvent
(42) Other impurities
(43) Residue on evaporation
(44) Readily carbonizable substances
7. The following paragraphs were newly added toGeneral Notices:Paragraph 12: The item ``Manufacturing re-quirement'' was newly added in monograph in order to specify the requirements that should be noted on manufacturing processes such as con-trol of intermediates and manufacturing processes.
Paragraph 34: The specification for residual sol-vents was added.(3) Paragraph 35: The item ``Potential adultera-tion'' was added in monograph in order to describe control of harmful substances that was intentionally contaminated.
(4) Paragraph 40: The definitions of ``sterility'', ``sterilization'' and ``aseptic technique'' as sterility related terms were added.8. The following paragraphs of General Notices(1) Paragraph 5: Container under ``Containers and storage'' for preparations (excluding prepara-tions containing crude drugs as main active in-gredients) in the monographs were removed from the standards for conformity.
(2) Paragraph 48: The symbols ( ) were newly added as the ways to indicate the part being not harmonized among three pharmacopoeias in order to distinguish ``JP local requirements'' from ``non-harmonized attributes/provisions among three pharmacopoeias''.
(3) Other descriptions were improved.
9. To Paragraph 1 of General Rules for Crude Drugs the following items were added:
(1) Codonopsis Root
(2) Hedysarum Root
(3) Salvia Miltiorrhiza Root
10. The following paragraphs were newly added to General Rules for Preparations:
``[2] General Notices for Packaging of Prepara-tions'' which describe the fundamental requirements for packaging of preparations in order to improve the terminology, definitions and specifications for packag-ing of preparation.
11. The General Rules for Preparations was revised as follows in general:
(1) General Notices for Preparations (8): The description of sterile preparations; ``sterile preparations'', ``terminal sterilization'' and ``aseptic processing'' was added.
(2) General Notices for Preparations (10): The description of containers and packaging for preparations was deleted.
(3) Monographs for Preparations (2): The descrip-tion of ``containers and packaging'' was delet-ed.
(4) Monographs for Preparations (3): The defini-tion of preparation in single-dose package was described.
(5) Other descriptions were improved.12. The following items were newly added to General Tests, Processes and Apparatus:
(1) 2.64 Glycosylation Analysis of Glycoprotein
(2) 2.65 Methods for Color Matching
(3) 3.05 Water-Solid Interactions: Determination of Sorption-Desorption Isotherms and of Water Activity
(4) 6.12 Methods of Adhesion Testing
(5) 6.13 Release Test for Preparations for Cutane-
ous Application
13. The following items in General Tests, Processes and Apparatus were revised:
(1) 2.21 Nuclear Magnetic Resonance Spectroscopy
