SC IV F. Pharmacopoeial Harmonisation

(Ph. Eur. general texts 5.8)

This general chapter is included for guidance of users.

It provides information on the degree of harmonisation of various general chapters and monographs of the European Pharmacopoeia and those of the Japanese Pharmacopoeia and United States Pharmacopeia.

This information reflects:

— for certain general chapters, the status observed for a given edition of the corresponding regional texts and any notification of regulatory acceptance by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH);

— for other general chapters and for monographs on excipients, the decision taken by the 3 regional pharmacopoeias when the harmonised text was signed off.

However, it remains the ultimate responsibility of the user to verify the current content of the texts in force in the respective pharmacopoeias.

The chapter does not affect in any way the status of the monographs and general chapters as the authoritative reference in any case of doubt or dispute where compliance with the European Pharmacopoeia is required.

The European Pharmacopoeia Commission recognises the utility of working with other pharmacopoeial bodies to develop harmonised monographs and general chapters. Such harmonisation is fully compatible with the declared aims of the Commission and has benefits of different kinds, notably the simplification and rationalisation of quality control methods and licensing procedures. Such harmonisation also enhances the benefits of the work of ICH and the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), since some of the guidelines developed depend on pharmacopoeial general chapters for their application.

Work on harmonisation is carried out by a well-defined but informal process in the Pharmacopoeial Discussion Group (PDG), in which the European Pharmacopoeia, the Japanese Pharmacopoeia and the United States Pharmacopeia are associated. Information is given in this general chapter on items that have been dealt with by the PDG:

— where harmonisation of general chapters is carried out, the aim is to arrive at interchangeable methods or requirements so that demonstration of compliance using a general chapter from one of the 3 pharmacopoeias implies that the same result would be obtained using the general chapter of either of the other pharmacopoeias; when a formal declaration of interchangeability has been recommended by ICH, it will be indicated in this general chapter;

— where harmonisation of monographs is carried out, the aim is to arrive at identical requirements for all attributes of a product; for some products it can be extremely difficult to achieve complete harmonisation, for example because of differences in legal status and interpretation; it has therefore appeared worthwhile to the PDG to approve and publish monographs in which as many attributes as possible are harmonised.

Information on any non-harmonised attributes/provisions and on any local requirements, i.e. attributes/provisions that are present only in the Ph. Eur. text, is included in this general chapter. The non-harmonised attributes/provisions are placed between black diamonds (♦♦) in the corresponding Ph. Eur. texts, while the local requirements are placed between white diamonds (♢♢).

The non-mandatory Functionality-related characteristics section is specific to the Ph. Eur.; it is not subject to pharmacopoeial harmonisation and is therefore not placed between black or white diamonds.

The 3 pharmacopoeias have undertaken not to make unilateral changes to harmonised monographs and general chapters but rather to apply the agreed revision procedure whereby all partners adopt a revision simultaneously.

General Chapters

The documents signed-off by the PDG cover the technical content of the text and each party adapts them as necessary to conform to the usual presentation of the pharmacopoeia in question; such adaptation includes stipulation of the particular pharmacopoeia′s reference materials and general chapters.

2.2.31. Electrophoresis

The following comparative commentary refers to the texts 23. SDS-Polyacrylamide Gel Electrophoresis in the Japanese Pharmacopoeia XV and <1056> Biotechnology-derived Articles – Polyacrylamide Gel Electrophoresis in the United States Pharmacopeia USP31 NF26 2^nd Supplement, and chapter 2.2.31. Electrophoresis in the European Pharmacopoeia.

In the Ph. Eur. the harmonised chapter has been included as a section entitled Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), within a more general chapter entitled Electrophoresis. The general chapter includes other parts: General principle, Free or moving boundary electrophoresis, Zone electrophoresis using a supporting medium, and Polyacrylamide rod gel electrophoresis, which are not within the scope of pharmacopoeial harmonisation. The corresponding parts have been placed between black diamonds (♦♦).

The above differences in the Ph. Eur. text do not affect harmonisation as the general chapter provides additional information.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

2.2.34. THERMAL ANALYSIS

As a result of the process of pharmacopoeial harmonisation, the following reflects the agreement reached by the Ph. Eur., the JP and the USP.

Harmonised provisions

Non-harmonised provisions

Local requirements

Thermogravimetry can be used as an alternative method for 2.41 Loss on Drying Test or 2.48 Water Determination (Karl Fischer Method). However, it must be confirmed beforehand that no volatile component except for water is included in the test specimen when thermogravimetry is used as an alternative method for water determination (Karl Fischer method). (JP)

(sign-off date: 26 June 2014)

2.2.47. Capillary electrophoresis

As a result of an evaluation of the texts 4. Capillary Electrophoresis in the Japanese Pharmacopoeia XV and <1053> Biotechnology-derived articles – Capillary Electrophoresis in the United States Pharmacopeia USP33 NF28, and chapter 2.2.47. Capillary electrophoresis in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

2.2.54. Isoelectric focusing

As a result of an evaluation of the texts 9. Isoelectric Focusing in the Japanese Pharmacopoeia XV and <1054> Biotechnology-derived articles – Isoelectric Focusing in the United States Pharmacopeia USP33 NF28, and chapter 2.2.54. Isoelectric focusing in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

2.2.55. Peptide mapping

The following comparative commentary refers to the texts 15. Peptide Mapping in the Japanese Pharmacopoeia XV and <1055> Biotechnology-derived Articles – Peptide Mapping in the United States Pharmacopeia USP31 NF26 2^nd Supplement, and chapter 2.2.55. Peptide mapping in the European Pharmacopoeia.

Validation (USP)

The USP has entitled this part System Suitability. This terminology has been accepted by the 3 pharmacopoeias.

The use of peptide mapping for genetic stability evaluation (USP)

This additional section does not impact harmonisation since it is used only in development.

The above differences in the USP text do not affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

2.2.56. Amino acid analysis

The following comparative commentary refers to the texts 1. Amino Acid Analysis in the Japanese Pharmacopoeia XV and <1052> Biotechnology-derived Articles – Amino Acid Analysis in the United States Pharmacopeia USP31 NF26 1^st Supplement, and chapter 2.2.56. Amino acid analysis in the European Pharmacopoeia.

Methodologies of amino acid analysis: general principles (USP)

The USP has replaced ‘6-aminoquinolyl-N-hydroxysuccinimidyl carbamate or o-phthalaldehyde’ with ‘6-aminoquinolyl-N-hydroxysuccinimidyl carbonate’.

These reagents are different but compatible and the use of one or the other does not affect harmonisation.

The USP has added a detailed example to describe each method listed below:

— Method 1: post-column ninhydrin detection;

— Method 2: post-column OPA derivatisation;

— Method 3: pre-column PITC derivatisation;

— Method 4: pre-column AQC derivatisation;

— Method 5: pre-column OPA derivatisation;

— Method 6: pre-column DABS-Cl derivatisation;

— Method 7: pre-column FMOC-Cl derivatisation;

— Method 8: pre-column NBD-F derivatisation.

The above examples are given for further information and do not affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

2.4.14. Sulfated ash

The following comparative commentary refers to the texts 2.44 Residue on Ignition Test in the Japanese Pharmacopoeia XV and <281> Residue on Ignition in the United States Pharmacopeia USP32 NF27 1^st Supplement, and chapter 2.4.14. Sulfated ash in the European Pharmacopoeia.

The JP has added a non-harmonised introductory part, included between black diamonds, at the beginning of this chapter. It is given for further information and therefore does not affect harmonisation.

The USP text allows for the test to be performed at an ignition temperature other than 600 ± 50 °C if prescribed in an individual monograph. In the same way, a sample mass different from the usual quantity of 1-2 g can be used if prescribed in an individual monograph.

The USP has added a section, included between black diamonds, on the use of a muffle furnace and its calibration.

The above differences in the USP text do not affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

NOTE ICH has declared this method interchangeable within the ICH regions.

2.6.1. STERILITY

The following comparative commentary refers to the texts 4.06 Sterility Test in the partial revision of the Japanese Pharmacopoeia XV made official March 31, 2009, by the Ministry of Health, Labour and Welfare Ministerial Notification No. 190 and <71> Sterility Tests in the United States Pharmacopeia as presented in Pharmacopeial Forum, Volume 34(6), Interim Revision Announcement No. 6, December 1, 2008, official on May 1, 2009, and chapter 2.6.1. Sterility in the European Pharmacopoeia.

The USP has added requirements that cover either pharmacy bulk packages of antibiotics or medical devices. The corresponding parts, which are not within the scope of pharmacopoeial harmonisation, have been placed between black diamonds (♦♦).

The JP has deleted the requirements for ‘Catgut and other surgical sutures for veterinary use’ in Table 2, in the section ‘Direct inoculation of the culture medium’ and in Table 3. Catgut and other surgical sutures are outside the scope of the JP.

The above differences in the JP and USP texts do not affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

NOTE ICH has declared this method interchangeable within the ICH regions.

2.6.12. Microbiological examination of non-sterile products: microbial enumeration tests

As a result of an evaluation of the texts 4.05 Microbiological Examination of Non-sterile Products: I. Microbiological Examination of Non-sterile Products – Microbial Enumeration Tests in the Japanese Pharmacopoeia XV 1^st Supplement and <61> Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests in the United States Pharmacopeia USP30 NF25, and chapter 2.6.12. Microbiological examination of non-sterile products: microbial enumeration tests in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

NOTE ICH has declared this method interchangeable within the ICH regions.

2.6.13. Microbiological examination of non-sterile products: test for specified micro-organisms

As a result of an evaluation of the texts 4.05 Microbiological Examination of Non-sterile Products: II. Microbiological Examination of Non-sterile Products – Test for Specified Micro-organisms in the Japanese Pharmacopoeia XV 1^st Supplement and <62> Microbiological Examination of Non-sterile Products: Test for Specified Micro-organisms in the United States Pharmacopeia USP30 NF25, and chapter 2.6.13. Microbiological examination of non-sterile products: test for specified micro-organisms in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

NOTE ICH has declared this method interchangeable within the ICH regions.

2.6.14. BACTERIAL ENDOTOXINS

As a result of an evaluation of the texts 4.01 Bacterial Endotoxin Test in the Japanese Pharmacopoeia XVI and <85> Bacterial Endotoxin Test in the United States Pharmacopoeia USP33, and chapter 2.6.14. Bacterial endotoxins in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

NOTE ICH has declared these texts interchangeable within the ICH regions subject to the conditions detailed below.

1. Any of the 3 techniques can be used for the test. In the event of doubt or dispute, the gel-clot limit test should be used to make the final decision on compliance for the product being tested.

2. The USP, JP and Ph. Eur. reference standards are considered interchangeable as they have been suitably calibrated against the WHO (World Health Organization) International Standard for Endotoxin.

3. In the section Photometric quantitative techniques - Preparatory testing - Test for interfering factors, the user should perform the test on solutions A, B, C and D on at least 2 replicates using the optimal conditions as recommended by the lysate manufacturer.

2.9.1. DISINTEGRATION OF TABLETS AND CAPSULES

The following comparative commentary refers to the texts 6.09 Disintegration Test in the Japanese Pharmacopoeia XV and <701> Disintegration in the United States Pharmacopeia USP32 NF27 1^st Supplement, and chapter 2.9.1. Disintegration of tablets and capsules (Test A) in the European Pharmacopoeia.

In the Ph. Eur. chapter, test A corresponds to the harmonised chapter while test B does not and is intended for tablets and capsules that are greater than 18 mm long. Test B is not within the scope of pharmacopoeial harmonisation and has been placed between black diamonds (♦♦).

The JP and USP specify procedures and acceptance criteria for different types of dosage forms. The equivalent statements are included in the Ph. Eur. general monographs on dosage forms. These statements are not within the scope of pharmacopoeial harmonisation.

In addition, the JP describes an auxiliary tube, and a metal plate to secure the glass tubes. This has been placed between black diamonds (♦♦). The use of this tube and this plate may have an impact on hydrodynamics and thus may affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

NOTE ICH has declared this method interchangeable within the ICH regions subject to the conditions detailed below.

For tablets and capsules larger than 18 mm long, for which a different apparatus is used, the disintegration test is not considered to be interchangeable in the 3 regions.

The test for disintegration is not considered to be interchangeable in the 3 regions for dosage forms referred to in the pharmacopoeias as delayed-release, gastro-resistant or enteric-coated.

2.9.3. DISSOLUTION TEST FOR SOLID DOSAGE FORMS

As a result of the process of pharmacopoeial harmonisation, the following reflects the agreement reached by the Ph. Eur., the JP and the USP.

Harmonised provisions

Local requirements

— Where dissolution failure occurs for dosage forms employing gelatin, the test may be repeated with the addition of enzymes (USP)

— The use of USP calibrators for the calibration of dissolution apparatus is specified (USP)

— Neither Apparatus 3, nor sections related to delayed-release dosage forms are included (JP)

— Procedure, Apparatus 1 and 2: “The test may also be carried out with the thermometer in place, provided it is shown that results equivalent to those obtained without the thermometer are obtained.” ( Ph. Eur.)

— The procedure and acceptance criteria for pooled dissolution are specified (USP)

— The use of larger vessels in Apparatus 1 and 2 is accepted: “for a nominal volume of 2 L, the height is 280 mm to 300 mm and its inside diameter is 98 mm to 106 mm; and for a nominal capacity of 4 L, the height is 280 mm to 300 mm and its inside diameter is 145 mm to 155 mm.” (USP)

Local requirements have been placed between white diamonds (♢♢) in Ph. Eur. chapter.

The terminology used to describe the dosage forms has not been harmonised:

NOTE ICH has declared this method interchangeable within the ICH regions subject to the conditions detailed below.

1. The declaration of interchangeability applies to the Basket Apparatus (Apparatus 1), the Paddle Apparatus (Apparatus 2), and the Flow-Through Cell. The Flow-Through Cell should be referred to in the dossier by an unambiguous descriptive title or compendial reference because it is referred to by different numbers in the three pharmacopoeias.

2. The Dissolution Test is not considered to be interchangeable in the ICH regions when enzymes are used in the media.

3. The dissolution apparatus should be appropriately calibrated to ensure compliance with regional good manufacturing practice (GMP) requirements. For example, an appropriately designed and executed mechanical calibration strategy should be in compliance with good manufacturing practice requirements.

4. The Dissolution Test is not considered to be interchangeable in the three ICH regions for dosage forms referred to in the regional compendia as delayed-release, gastro-resistant, or enteric-coated.

5. Validation studies should be conducted to demonstrate that the test results are not adversely affected if the thermometer is to remain in the dissolution vessel per regional good manufacturing practice (GMP).

6. The Dissolution Test is not considered to be interchangeable in the ICH regions for JP Interpretation 2.

7. The Dissolution Test is not considered to be interchangeable in the ICH regions for use of large vessels (greater than 1 litre).

8. Product-specific parameters such as media, stirring rate, sampling time, and the use and type of sinkers should be specified and justified in the application dossier.

(Sign-off date: 10 June 2010)

2.9.7. Friability of uncoated tablets

As a result of an evaluation of the texts 26. Tablet Friability Test in the Japanese Pharmacopoeia XV and <1216> Tablet Friability in the United States Pharmacopeia USP31 NF26 1^st Supplement, and chapter 2.9.7. Friability of uncoated tablets in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

2.9.17. Test for extractable volume of parenteral preparations

The following comparative commentary refers to the texts 6.05 Test for Extractable Volume of Parenteral Preparations in the Japanese Pharmacopoeia XV and <1> Injections in the United States Pharmacopeia USP32 NF27 1^st Supplement, and chapter 2.9.17. Test for extractable volume of parenteral preparations in the European Pharmacopoeia.

The JP has added a non-harmonised introductory part, included between black diamonds, at the beginning of this chapter. It is given for further information and does not affect harmonisation.

The USP has included this test in general chapter <1> Injections, under a specific part entitled Determination of Volume of Injection in Containers. This does not affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

NOTE ICH has declared this method interchangeable within the ICH regions.

2.9.19. PARTICULATE CONTAMINATION: SUB-VISIBLE PARTICLES

The following comparative commentary refers to the texts 6.07 Insoluble Particulate Matter Test for Injections in the Japanese Pharmacopoeia XV (corrected version dated September 2007) and <788> Particulate Matter in Injections in the United States Pharmacopeia USP32 NF27 2^nd Supplement, and chapter 2.9.19. Particulate contamination: sub-visible particles in the European Pharmacopoeia.

The USP specifies that system suitability can be verified using USP Particle Count RS. This statement is not within the scope of pharmacopoeial harmonisation. It has been placed between black diamonds (♦♦) and it does not affect harmonisation.

The JP includes a detailed section on calibration of the apparatus. In particular, requirements for the quality of particle-free water are given, which differ from those stated in the USP (see section Reagents, Indicators and Solutions) and in the Ph. Eur. (see chapter 4.1.1). The section on calibration is not within the scope of pharmacopoeial harmonisation. It has been placed between black diamonds (♦♦) and it does not affect harmonisation.

In addition, the JP describes more stringent acceptance criteria for parenteral preparations having a nominal volume of 100 mL. This was acknowledged by the PDG as a non-harmonised item. It has been placed between black diamonds (♦♦). The acceptance criteria for parenteral preparations having a nominal volume of 100 mL are therefore considered non-harmonised.

The texts of the 3 pharmacopoeias are therefore considered harmonised except for the acceptance criteria for parenteral preparations having a nominal volume of 100 mL.

NOTE ICH has declared this method interchangeable within the ICH regions except the acceptance criteria for parenteral preparations having a nominal volume of 100 mL.

2.9.26. Specific surface area by gas adsorption

The following comparative commentary refers to the texts 3.02 Specific Surface Area by Gas Adsorption in the Japanese Pharmacopoeia XV and <846> Specific Surface Area in the United States Pharmacopeia USP31 NF26 1^st Supplement, and chapter 2.9.26. Specific surface area by gas adsorption in the European Pharmacopoeia.

The JP has chosen to express all the temperatures of this chapter in degrees Celsius.

Multi-point measurement (JP)

The JP does not state the meaning of the 22400 constant in the definition of the specific surface area S and does not require a test to determine the linearity of the method.

Single-point measurement (JP)

The JP does not state the equivalent quantity of gas corresponding to the value of P/P₀, which is less precise (0.30) than in the other pharmacopoeias (0.300).

The JP does not assume the material constant C to be invariant.

Measurements (JP)

The JP does not specify the temperature required to perform the test for either method.

The JP limits its volumetric method to classical instruments and does not take alternative instruments into account.

The above differences in the JP text might affect harmonisation.

Therefore only the texts of the Ph. Eur. and the USP are considered harmonised.

2.9.36. Powder flow

The following comparative commentary refers to the texts 18. Powder Flow in the Japanese Pharmacopoeia XV and <1174> Powder Flow in the United States Pharmacopeia USP31 NF26 1^st Supplement, and chapter 2.9.36. Powder flow in the European Pharmacopoeia.

Flow through an orifice (JP)

The JP limits the use of orifices to classical ones and does not allow vibrators or moving orifices. A test result using the JP method will be compatible with the Ph. Eur. and the USP. A Ph. Eur. or USP test result will not comply with the JP when a vibrator or moving orifice is used.

2.9.37. Optical microscopy

As a result of an evaluation of the texts 3.04 Particle Size Determination in the Japanese Pharmacopoeia XV and <776> Optical Microscopy in the United States Pharmacopeia USP31 NF26 2^nd Supplement, and chapter 2.9.37. Optical microscopy in the European Pharmacopoeia, the texts of the 3 pharmacopoeias are considered harmonised.

2.9.38. Particle-size distribution estimation by analytical sieving

The following comparative commentary refers to the texts 3.04 Particle Size Determination in the Japanese Pharmacopoeia XV and <786> Particle-size Distribution Determination by Analytical Sieving in the United States Pharmacopeia USP31 NF26 1^st Supplement, and chapter 2.9.38. Particle-size distribution estimation by analytical sieving in the European Pharmacopoeia.

Sieving methods - Dry sieving method (JP)

The JP permits any powder on the down surface of the sieve to be brushed and combined with the fraction of the next sieve.

The above difference in the JP text might affect harmonisation.

Therefore only the texts of the Ph. Eur. and the USP are considered harmonised.

2.9.40. UNIFORMITY OF DOSAGE UNITS

As a result of the process of pharmacopoeial harmonisation, the following reflects the agreement reached by the Ph. Eur., the JP and the USP.

Harmonised provisions

Non-harmonised provisions

The following statement in the introduction is not accepted and will not be included by the USP.

“Alternatively, products listed in item (4) above that do not meet the 25 mg/25% threshold limit may be tested for uniformity of dosage units by Mass Variation instead of the Content Uniformity test if the concentration relative standard deviation (RSD) of the drug substance in the final dosage units is not more than 2%, based on process validation data and development data, and if there has been regulatory approval of such a change. The concentration RSD is the RSD of the concentration per dosage unit (w/w or w/v), where concentration per dosage unit equals the assay result per dosage unit divided by the individual dosage unit weight. See the RSD formula in Table 2.”

The corresponding statement in the Ph. Eur. has been placed between black diamonds (♦♦).

Local requirements

The Ph. Eur. prescribes in its relevant general monographs on dosage forms that preparations supplied in single-dose containers that represent 1 dose of medicinal product and are intended for transdermal delivery of the active substance(s) in view of a systemic effect comply with general chapter 2.9.40. Uniformity of dosage units. Therefore the wording has been adapted as follows:

“Unless otherwise stated, the uniformity of dosage units specification is not intended to apply to solutions, suspensions, emulsions or gels in single-dose containers intended for local action following cutaneous administration.”

The Ph. Eur. excludes multivitamin, single-vitamin and trace-element preparations from the test for content uniformity.

In the Ph. Eur. section on mass variation the procedure for liquid dosage forms also applies to semi-solid dosage forms.

All local requirements have been placed between white diamonds (♢♢) in Ph. Eur. chapter.

NOTE ICH has declared this method interchangeable within the ICH regions subject to the conditions detailed below.

1. Unless the 25 mg/25% threshold limit is met, the use of the Mass/Weight Variation test as an alternative test for Content Uniformity is not considered interchangeable in all ICH regions.

2. For specific dosage forms that appear in local text in the pharmacopoeias by enclosing the text in black diamond symbols, application of the Uniformity of Dosage Units test is not considered interchangeable in all ICH regions.

3. If a correction factor is called for when different procedures are used for assay of the preparation and for the Content Uniformity test, the correction factor should be specified and justified in the application dossier.

(sign-off date: 4 November 2015)

5.1.4. Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use

The following comparative commentary refers to the texts 12. Microbial Attributes of Non-sterile Pharmaceutical Products in the Japanese Pharmacopoeia XV 1^st Supplement and <1111> Microbiological Attributes of Non-sterile Pharmaceutical Products in the United States Pharmacopeia USP30 NF25, and chapter 5.1.4. Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use in the European Pharmacopoeia.

Two special Ph. Eur. provisions are included within Table 5.1.4.-1: for oral dosage forms containing raw materials of natural origin and for premixes for medicated feeding stuffs for veterinary use. Also, a reference to chapter 5.1.8 giving recommended acceptance criteria for the microbiological quality of herbal medicinal products for oral use and extracts used in their preparation is included in the text. The corresponding parts, which are not within the scope of pharmacopoeial harmonisation, have been placed between black diamonds (♦♦).

The above differences in the Ph. Eur. text do not affect harmonisation.

The texts of the 3 pharmacopoeias are therefore considered harmonised.

NOTE ICH has declared these texts interchangeable within the ICH regions.

Monographs

As a result of the process of pharmacopoeial harmonisation, the following reflects the agreement reached by the Ph. Eur., the JP and the USP.

Reagents and reference materials

Each pharmacopoeia adapts the text to take account of local reference materials and reagent specifications.

CARMELLOSE (2360)

Harmonised attributes

Non-harmonised attributes

Characters/Description, Heavy metals, Storage/Containers and storage/Packaging and storage

Local requirements

(sign-off date: 9 November 2011)

CELLULOSE ACETATE (0887)

Harmonised attributes

JP will not include this monograph and has therefore not participated in the harmonisation.

Non-harmonised attributes

Local requirements

Characters ( Ph. Eur.)

(sign-off date: 26 May 2016)

CELLULOSE ACETATE PHTHALATE (0314)

Harmonised attributes

Non-harmonised attributes

Characters/Description and solubility/Description, Heavy metals, Packaging and storage

(sign-off date: 9 November 2010)

ETHANOL (96 PER CENT) (1317)

Harmonised attributes

Definition and Relative density

Each pharmacopoeia specifies a different range for the content; the values for relative density vary accordingly and, in addition, are expressed at different temperatures.

Non-harmonised attributes

Characters/Description

Local requirements

Identification tests C and D ( Ph. Eur.), List of impurities (Ph. Eur.), Expiration date (JP)

(sign-off date: 7 November 2012)

ETHANOL, ANHYDROUS (1318)

Harmonised attributes

Definition and Relative density

Each pharmacopoeia specifies a different range for the content; the values for relative density vary accordingly and, in addition, are expressed at different temperatures.

Non-harmonised attributes

Characters/Description

Local requirements

Identification tests C and D ( Ph. Eur.), List of impurities (Ph. Eur.), Expiration date (JP)

(sign-off date: 7 November 2012)

ETHYLCELLULOSE (0822)

Harmonised attributes

Non-harmonised attributes

Characters/Description, Containers and storage/Packaging and storage

Local requirements

Identification (compliance with limits of assay) (Ph. Eur.), Heavy metals (JP)

(sign-off date: 26 May 2016)

GELATIN (0330)

Gelling grade

Harmonised attributes

Non-harmonised attributes

Definition (JP) ‘and/or enzymatic hydrolysis’ not included

Characters/Description

Local requirements

Heavy metals (JP), Arsenic (JP), Containers (JP), Labelling (method of hydrolysis) (USP)

(sign-off date: 26 October 2016)

Non-gelling grade

Harmonised attributes

JP has signed the draft for non-gelling grade but will not implement it as this grade is hardly ever used in Japan.

Non-harmonised attributes

Characters

Local requirements

Labelling (method of hydrolysis) (USP)

(sign-off date: 26 October 2016)

GLUCOSE (0177)

Harmonised attributes

Non-harmonised attributes

Characters/Description, Heavy metals, Containers and storage/Packaging and storage, Labelling

Local requirements

First identification (specific optical rotation) ( Ph. Eur.), Second identification (TLC, colour reaction) ( Ph. Eur.), Pyrogens ( Ph. Eur.), Identification (colour reaction) (JP), Specific optical rotation (JP), Identification (infrared absorption spectrophotometry) (USP)

(sign-off date: 4 November 2015)

GLUCOSE MONOHYDRATE (0178)

Harmonised attributes

Non-harmonised attributes

Characters/Description, Heavy metals, Containers and storage/Packaging and storage, Labelling

WHEAT STARCH (0359)

Harmonised attributes

Non-harmonised attributes

Characters/Description, Packaging and storage/Containers and storage

Local requirements

Foreign matter ( Ph. Eur.), Absence of Salmonella ( Ph. Eur.), Total protein (catalyst: TiO₂ instead of Se) (JP)

(sign-off date: 4 November 2015)