Farmacopéia Japonesa

Farmacopéia Japonesa

(Parte 1 de 12)

The Ministry of Health, Labour and Welfare Ministerial Notication No. 285

Pursuant to Paragraph 1, Article 41 of the Pharmaceutical AŠairs Law (Law No. 145, 1960), the Japanese Pharmacopoeia (hereinafter referred to as new Pharmacopoeia''), which has been established as follows*, shall be applied on April 1, 2006, and the Ministry of Health, Labour and Welfare Ministerial Notication No. 1 (Matter of Establishing the Japanese Pharmacopoeia; hereinafter referred to as previous Pharmacopoeia''), issued in 2001, shall be abolished on March 31, 2006. However, in the case of drugs which are listed in the new Pharmacopoeia (limited to those listed in the previous Pharmacopoeia) and drugs which have been approved as of April 1, 2006 as prescribed under Paragraph 1, Article 14 of the same law [including drugs the Minister of Health, Labour and Welfare species (the Ministry of Health and Welfare Ministerial Notication No. 104, 1994) as those exempted from marketing approval pursuant to Paragraph 1, Article 14 of the Pharmaceutical AŠairs 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 September 30, 2007. 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 April 1, 2006 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 before and on September 30, 2007.

Jiro Kawasaki The Minister of Health, Labour and Welfare

Referring the next title to this book: The Japanese Pharmacopoeia''.

(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, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, at each Regional Bureau of Health and Welfare, and at each Prefectural O‹ce in Japan).

*The term as follows'' here indicates the contents of the Japanese Pharmacopoeia Fifteenth Edition from General Notices to Ultraviolet-visible Reference Spectra (p. 1 – 1654).

General Notices1
General Rules for Crude Drugs5
General Rules for Preparations7
General Tests, Processes and Apparatus17
1.01 Alcohol Number Determination17
1.02 Ammonium Limit Test19
1.03 Chloride Limit Test20
1.04 Flame Coloration Test20
1.05 Mineral Oil Test20
1.06 Oxygen Flask Combustion Method20
1.07 Heavy Metals Limit Test21
Kjeldahl Method)2
1.09 Qualitative Tests23
1.10 Iron Limit Test28
1.1 Arsenic Limit Test29
1.12 Methanol Test30
1.13 Fats and Fatty Oils Test31
1.14 Sulfate Limit Test3
1.15 Readily Carbonizable Substances Test3

CONTENTS The Japanese Pharmacopoeia, Fifteenth 1. Chemical Methods 1.08 Nitrogen Determination (Semimicro- 2. Physical Methods

2.01 Liquid Chromatography3
2.02 Gas Chromatography35
2.03 Thin-layer Chromatography37


2.2 Fluorometry40
2.24 Ultraviolet-visible Spectrophotometry41
2.25 Infrared Spectrophotometry43

Spectroscopic Methods 2.21 Nuclear Magnetic Resonance 2.23 Atomic Absorption

2.41 Loss on Drying Test4
2.42 Congealing Point Determination4
2.43 Loss on Ignition Test45
2.4 Residue on Ignition Test45
2.45 Refractive Index Determination46
2.46 Residual Solvents Test46
2.47 Osmolarity Determination46

Other Physical Methods 2.48 Water Determination (Karl Fischer

2.49 Optical Rotation Determination50
2.51 Conductivity Measurement53
2.52 Thermal Analysis54
2.53 Viscosity Determination56
2.54 pH Determination59
2.5 Vitamin A Assay60
2.58 X-Ray Powder Diffraction Method64
2.59 Test for Total Organic Carbon65
2.60 Melting Point Determination6
3.04 Particle Size Determination72

2.50 Endpoint Detection Methods in 2.56 Determination of Specific Gravity and 2.57 Boiling Point and Distilling Range 3. Powder Property Determinations 3.01 Determination of Bulk and Tapped 3.02 Specific Surface Area by Gas 3.03 Powder Particle Density 4. Biological Tests/Biochemical Tests/

4.01 Bacterial Endotoxins Test7
4.02 Microbial Assay for Antibiotics81
4.03 Digestion Test84
4.04 Pyrogen Test87
4.05 Microbial Limit Test8
4.06 Sterility Test93
5.01 Crude Drugs Test97
5.02 Microbial Limit Test for Crude Drugs100
6.02 Uniformity of Dosage Units106
Gastrointestinal Medicines109
Parenteral Preparations110
Ophthalmic Solutions113
6.09 Disintegration Test114

Microbial Tests 5. Tests for Crude Drugs 6. Tests for Preparations 6.01 Test for Metal Particles in Ophthalmic 6.03 Particle Size Distribution Test for 6.04 Test for Acid-neutralizing Capacity of 6.05 Test for Extractable Volume of 6.06 Foreign Insoluble Matter Test for 6.07 Insoluble Particulate Matter Test for 6.08 Insoluble Particulate Matter Test for 6.10 Dissolution Test.................................116

JP XVContents

7.02 Test Methods for Plastic Containers121
and Reverse Osmosis-Ultrafiltration128

7. Tests for Containers and Packing Materials 7.01 Test for Glass Containers for Injections..120 7.03 Test for Rubber Closure for Aqueous 8. Other Methods 8.01 Sterilization and Aseptic Manipulation, 9. Reference Standards; Standard Solutions;

Reagents, Test Solutions; Measuring Instruments, Appliances, Thermometers, etc.

9.01 Reference Standards129

Reference Standards

9.2 Standard Solutions143
9.23 Matching Fluids for Color145

Standard Solutions 9.21 Standard Solutions for Volumetric

9.41 Reagents, Test Solutions146
Test Papers, Crucibles, etc261
9.4 Reference Particles, etc261

Reagents, Test Solutions, etc. 9.42 Solid Supports/Column Packing for 9.43 Filter Paper, Filters for Filtration,

Measuring Instruments and Appliances,

Transmission Rate Calibration262
9.62 Measuring Instruments, Appliances262
9.63 Thermometers263
Official Monographs265
Crude Drugs1251
Infrared Reference Spectra1373–1518
Ultraviolet-visible Reference Spectra1519–1654

Thermometers, etc. 9.61 Optical Filters for Wavelength and

1. Amino Acid Analysis1655
2. Aristolochic Acid1662

General Information 3. Basic Requirements for Viral Safety of

listed in Japanese Pharmacopoeia1663
4. Capillary Electrophoresis1675
6. Disinfection and Sterilization Methods1680

Biotechnological/Biological Products 5. Decision of Limit for Bacterial 7. Guideline for Residual Solvents, Residual


Solvents Test, and Models for the Test in

8. International Harmonization

Pharmacopoeia Fifteenth Edition1684
9. Isoelectric Focusing1708
Particle Size1710
1. Media Fill Test1712
Pharmaceutical Products1715

Implemented in the Japanese 10. Laser Diffraction Measurement of 12. Microbial Attributes of Nonsterile 13. Microbiological Evaluation of Processing

Biotechnological/Biological Products1721
15. Peptide Mapping1724
16. pH Test for Gastrointestinal Medicine1727
18. Powder Flow1729
19. Preservatives-Effectiveness Tests1732

Areas for Sterile Pharmaceutical 14. Mycoplasma Testing for Cell Substrates used for the Production of 17. Plastic Containers for Pharmaceutical 20. Qualification of Animals as Origin of

Pharmaceutical Use1736

Animal-derived Medicinal Products provided in the General Notices of Japanese Pharmacopoeia and Other 21. Quality Control of Water for 2. Rapid Identification of Microorganisms

23. SDS-Polyacrylamide Gel Electrophoresis1742
24. Solid and Particle Densities1746
Sterilized Pharmaceutical Products1748
26. Tablet Friability Test1751

Based on Molecular Biological Method...1740 25. Sterility Assurance for Terminally 27. Terminal Sterilization and Sterilization 28. Test for Trace Amounts of Aluminum in

29. Total Protein Assay1756
30. Validation of Analytical Procedures1760

Trans Parenteral Nutrition (TPN)

Atomic Weight Table (2004)1763
Standard Atomic Weights 20041764
Index in Latin name1777

The 14th Edition of the Japanese Pharmacopoeia

(JP) was promulgated by Ministerial Notication No. 1 of the Ministry of Health, Labour and Welfare (MHLW) on March 30, 2001. To keep pace with progress in medical and pharmaceutical sciences, in November 2001, the Committee on JP established the basic principles for the preparation of the JP 15th Edition, setting out the characteristics and roles of the JP, the denite measures for the revision, the date of the revision, and the organization of the JP expert committees.

At the above Committee, the ve basic principles of

JP, which we refer to as the Five Pillars of JP'' were established as follows.: 1) Making the JP more substantial by including all drugs which are important from the viewpoint of health care and medical treatment; 2) Making prompt partial revision as necessary and facilitating smooth administrative operation; 3) Promoting international harmonization; 4) Ensuring transparency regarding the revision and dissemination to the public of the JP; 5) Promoting the introduction of new analytical technology and appropriate modications to existing science and technology, and promoting the improvement of reference standards.

It was agreed that the Committee on JP should make eŠorts, on the basis of the Five Pillars of JP, to ensure that theJ Pi su sede Šectively inh ealthc are and medical treatment, by seeking the understanding and cooperation for interested parties.

The JP should provide an o‹cial standard, being required to assure the quality of medicines in Japan in response to the progress of science and technology and medical demands at the time. It should dene the standards for specications, as well as the methods of testing to assure the overall quality of every drug 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 health and medical treatment.

The JP has been prepared with the aid of the knowledge and experience of many professionals in the pharmaceutical eld. Therefore, JP should have the characteristics of an o‹cial standard, which might be widely used by all parties concerned. It should provide information and understanding about the quality of drugs to the public, and it should be conducive to smooth and eŠective regulatory control of the quality of drugs, as well as promoting and maintaining international consistency and harmonization of technical requirements.

It was also agreed that JP articles should cover drugs which are important from the viewpoint of health care and medical treatment based on demand, frequency of use and clinical results. It should ensure prompt pharmacopeial listing after the introduction of drugs to the market.

A denite rule for selection of articles and a clariˆcation of criteria for selection were also established. The rule was described by the Pharmaceutical AŠairs and Food Sanitation Council (PAFSC) in an article entitled What the future Japanese Pharmacopoeia should be'' on December 2002. The target date for the publication of JP 15th Edition (the Japanese edition) was set as April 2006.

At the rst stage, JP Expert Committees were organized into the following twelve Panels and two subcommittees: Panel on the Principles of Revisions; Panel on the Selection of Articles; Panel on Nomenclature ; Panel on Pharmaceutical Excipients; First Panel on Chemical Drugs, Second Panel on Chemical Drugs; Panel on Biologicals; Panel on Biological Tests; Panel on Physico-Chemical Methods; Panel on Physical Methods; Panel on Preparations; Panel on Crude Drugs; First Sub-committee on the Principles of Revisions; First Sub-committee on Crude Drugs.

In November 2001, the JP Expert Committees were reorganized into the following eleven Panels in accordance with the recommendation of the PAFSC: Panel on the Principles of Revisions; Panel on Nomenclature; Panel on Pharmaceutical Excipients; Panel on Physico-Chemical Methods; Panel on Medicinal Chemicals; Panel on Biologicals; Panel on Biological Tests; Panel on Antibiotics; Panel on Crude Drugs; Sub-committee on the Principles of Revisions; Panel on International Harmonization (Pharmacopoeial Discussion Group (PDG) related Panel). Thereafter, the Panel on Pharmaceutical Water, Panel on Reference Standards, and three working groups under the Panel on Medicinal Chemicals were established to expedite discussion of revision drafts of Monographs.

In the Committee on JP, Mitsuru Uchiyama took the role of chairman from January 2001 to December 2002, Tadao Terao from January to June 2003, and Takao Hayakawa from July 2003 to March 2006.

i JP XVPreface

In addition to the regular revision every ve years in line with the basic principles for the preparation of the JP, it was agreed that partial revision should be done as necessary to take account of recent progress of science and in the interests of international harmonization.

In accordance with the above principles, the expert committees initiated deliberations on selection of articles, and revisions for General Notices, General Rules for Preparations, General Tests, Monographs ands o n.

Draft revisions covering subjects, the addition to

General Notices of a sentence In principle, unless otherwise specied, animals used as a source of materials for preparing pharmaceutical preparations must be healthy'' and the deletion of a monograph Phenacetin'' were examined by the Committee on JP in November 2001, followed by the PAFSC in December 2001, and then submitted to the MHLW.

Ther evisionw as promulgatedo nM arch 29, 2002 by

Ministerial Notication No.151 of the MHLW.

For draft revisions covering subjects in General

Notices, General Rules for Preparations, General Rules for Crude Drugs, General Tests and Monographs, deliberations were continued between June 2000 and February 2002, prepared for a supplement to the JP 14, examined by the Committee on JP in September 2002, followed by the PAFSC in December 2002, and then submitted to the Minister of MHLW. The supplement was named Supplement I to the JP 14th Edition'' and promulgated on December 27, 2002 by Ministerial Notication No. 395 of MHLW.

(Parte 1 de 12)