1. INTRODUCTION
1.1 Objective(s) of the Guideline
This document describes a process for the evaluation and recommendation by the Q4B Expert Working Group (EWG) of selected pharmacopoeial texts to facilitate their recognition by regulatory authorities for use as interchangeable in the ICH regions. Following favourable evaluations, ICH will issue topic-specific annexes with information about these texts and their implementation (the Q4B Outcomes). Implementation of the Q4B annexes is intended to avoid redundant testing by industry.
1.2 Background
When issuing Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances, and Q6B: Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, ICH recognized that full use and value of both ICH Guidelines would depend on the successful harmonisation of pharmacopoeial procedures and encouraged the work of the Pharmacopoeial Discussion Group (PDG).
1.2.1 The Pharmacopoeial Discussion Group (PDG)
The PDG, founded in 1990, consists of representatives from the European Directorate for the Quality of Medicines (EDQM) in the Council of Europe; the Ministry of Health, Labour and Welfare (MHLW) of Japan; and the United States Pharmacopoeial Convention, Inc (USP). The PDG produces harmonised pharmacopoeial texts through independent public comment and consultation. The PDG reports on the status of its harmonisation efforts at ICH meetings as appropriate.
1.2.2 The Q4B Expert Working Group (EWG)
In November 2003, ICH established the Q4B EWG to evaluate and recommend pharmacopoeial texts that are proposed for use in the three ICH regions. The Q4B EWG anticipates that the PDG will be the principal source of pharmacopoeial text proposals. There might be an occasion where not all three parties of the PDG participate in a harmonisation effort for a specific pharmacopoeial text. In such a case, the Q4B EWG can accept proposals from one or two PDG pharmacopoeias.
1.3 Scope of the Guideline
Initially, the Q4B process will focus on evaluating the 11 General Test Chapters discussed during the development of ICH Q6A (refer to Attachment I). Many other pharmacopoeial harmonisation proposals are being developed and could also be considered for Q4B evaluation.
1.4 General Principles
The EWG will evaluate pharmacopoeial text proposals and assess the regulatory impact of the proposals. The Q4B EWG will continue its dialogue with the PDG as necessary during the Q4B process. Following its evaluation, the Q4B EWG will reach a conclusion and make a recommendation on the use of the text in the ICH regions which will be conveyed to the ICH Steering Committee. For each proposal that is favourably evaluated, the Q4B EWG intends to develop a topic-specific annex to the Q4B Guideline following the ICH step process. The annex will provide information on how the pharmacopoeial texts can be used in the ICH regions. Each annex will be issued as a stand-alone companion document to the Q4B guideline.
To preserve transparency, the Q4B EWG should be notified of any revisions to a pharmacopoeial text that has been submitted to the Q4B evaluation process. Any change to pharmacopoeial text that has been proposed to, or recommended through, the Q4B evaluation process will prompt a Q4B EWG review to assess both the merit of the change and the appropriateness of any subsequent Q4B activity related to that text.
2. GUIDELINES
2.1 Q4B Evaluation Process
The process begins with a document submission to the Q4B EWG. For PDG proposed pharmacopoeial text, the document submission should be provided as soon as possible after PDG Stage 5B sign-off (refer to Attachment II). The document submission should outline any issues for resolution and should contain any appropriate supporting data.
When the Q4B evaluation process results in a conclusion and recommendation that the pharmacopoeial text can be used as interchangeable in the ICH regions, a topic-specific Q4B annex will be issued following the steps in the ICH process as detailed below.
2.1.1 Step 1
Each Q4B party independently evaluates the documents for regulatory impact. Additional discussion within the Q4B EWG, and/or communication/dialogue with the submitting party (e.g., the PDG), might be warranted to resolve any issues that surfaced during the evaluation (see example in the figure below).
When the Q4B evaluation process results in a recommendation that the pharmacopoeial text can be used as interchangeable in the ICH regions, the Q4B EWG prepares and signs off on a draft Q4B annex, which is submitted to the Steering Committee for adoption at Step 2.
2.1.2 Step 2
The Steering Committee agrees, based on the report of the Q4B EWG, that there is sufficient scientific consensus on the technical issues for the draft annex to proceed to Step 3 regulatory consultation and discussion.
2.1.3 Step 3
The draft Q4B annex is made available for regulatory consultation in the three regions (generally for 3 months). The regulatory consultation and discussion should focus on the Q4B Outcome in the annex. The Q4B EWG can revise the annex based on comments received and submits a final draft of the annex to the ICH Steering Committee.
2.1.4 Step 4
The ICH Steering Committee adopts the annex and issues it as a stand-alone companion document to the ICH Q4B guideline.
2.1.5 Step 5
The annex moves to the regional regulatory implementation step.
2.2 Annex Contents
The Q4B annexes will contain the following information at a minimum. Other information might be incorporated on a case-by-case basis.
• Topic title;
• Introduction;
• Q4B Outcome;
• As appropriate, statements that will assist in the use of the referenced pharmacopoeial text by stakeholders;
• Implementation timelines indicating regulators' advice on when stakeholders can begin using the pharmacopoeial text as interchangeable;
• References to methods and acceptance criteria, as appropriate.
2.3 Use of the Pharmacopoeial Text
After a regulatory ICH region has implemented the Q4B annex, the official pharmacopoeial texts referenced in the annex can be used as interchangeable in that region. Any general and/or specific implementation recommendations for a regulatory region will be provided in the Q4B topic specific annex as part of Section 4. Considerations for Implementation. The basic information will be as provided below:
2.3.1 Considerations for Implementation
General consideration: When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2 of the annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
In addition to these general considerations, specific information for each regulatory region can assist the implementation in that region. Each regulatory region will provide such notification to its stakeholders in conjunction with regional implementation of the annex.
FDA consideration: Based on the recommendation above, and in accordance with the conditions set forth in the annex, the pharmacopoeial texts as referenced in Section 2 of the annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
EU consideration: For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2 of the annex, in accordance with the conditions set out in the annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter [chapter name and Ph. Eur. Reference], on the basis of the declaration of interchangeability made above.
MHLW consideration: The pharmacopoeial texts as referenced in Section 2 of the annex can be used as interchangeable in accordance with the conditions set out in the annex. Details of implementation requirements will be provided in the notification by MHLW when the specific annex is implemented.
3. GLOSSARY
Document Submission
The working documents received from the PDG or one or more pharmacopoeial sources (USP, Ph. Eur., or JP) that contain the proposed pharmacopoeial text and any other support documents provided for Q4B evaluation.
Interchangeable
Where such status is indicated, any of the official texts from JP, EP, or USP can be substituted one for the other (appropriately referenced) in the ICH regions for purposes of the pharmaceutical registration/approval process. Using any of the interchangeable methods, an analyst will reach the same accept or reject decisions irrespective of which PDG pharmacopeia is used.
PDG
The three-party Pharmacopoeial Discussion Group consisting of representatives from the European Directorate for the Quality of Medicines (EDQM) in the Council of Europe; the Ministry of Health, Labour and Welfare (MHLW) of Japan, and the United States Pharmacopoeial Convention, Inc (USP).
Pharmacopoeial text
The pharmacopoeial monographs, general test chapters, and analytical methods emanating from the three regional pharmacopoeias.
Q4B Outcome
Produced by the Q4B evaluation process; information concerning how the evaluated pharmacopoeial text can be used. The Q4B Outcome is included as part of the topic-specific Q4B annex developed as a result of each favourable evaluation.
Attachment I
General Chapters Discussed During ICH Q6A Development
Attachment II
PDG Document Submission Provided for ICH Q4B EWG Evaluation
This is an example of a document submission from the PDG:
The Coordinating Pharmacopoeia, on behalf of PDG, is asked to provide, as soon as possible after PDG Stage 5B sign-off and usually within six months, the following texts and information (termed the "document submission" as defined in the Guideline) to the Q4B EWG, via the ICH secretariat, with a copy to the Q4B EWG Rapporteur (for awareness):
1) The PDG sign-off document containing the PDG-harmonised text (PDG Stage 5B).
2) A Briefing Note dealing in particular with:
a. Residual differences between one or more of the pharmacopoeias, to include a commentary on any difference from the point of view of harmonisation;
b. Any specific issues relating to publication;
c. If any equivalency study was conducted, a summary of the outcome;
d. The projected publication and implementation schedule in each pharmacopoeia; and
e. Any additional information not covered above.
3) The texts as intended for adoption and publication in each pharmacopoeia together with a statement of any local differences with respect to the sign-off text.
4) Additional clarifying information is incorporated by one or more of the PDG pharmacopoeias in their respective information chapters on pharmacopoeial harmonisation. Therefore, the revised information chapter on harmonisation from each pharmacopoeia incorporating such information (in draft form where this is available) should accompany the provided documents.
If any changes occur or additional differences are discovered after submission to Q4B for evaluation, the Q4B EWG should be informed promptly by the pharmacopoeia concerned.
Q4B Annex 1 (R1)
EVALUATION AND RECOMMENDATION OF PHARMACOPOEIALTEXTS FOR USE IN THE ICH REGIONS ONRESIDUE ON
IGNITION/SULPHATED ASH GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Residue on Ignition/Sulphated Ash. The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 20414 Sulphated Ash, JP 2.44 Residue on Ignition Test, and USP <281> Residue on Ignition can be used as interchangeable in the ICH regions given the following:
2.1.1
2.1.1 Unless otherwise specified in a monograph, an appropriate sample weight is chosen, typically 1-2 g, to result in a level of residue sufficient to be accurately measurable by weight (typically 1 mg). If not specified in the monograph, the appropriate sample weight should be justified, and the sample weight and the acceptance criteria should be specified in the application dossier.
2.1.2
The muffle furnace should be appropriately calibrated to ensure compliance with regional GMP requirements.
2.2 Acceptance Criteria
The proposed texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. iming may differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1
General consideration: When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2
FDA consideration: Based on the recommendation above, and in accordance with the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3
EU consideration: For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter, Sulphated Ash: 20414, on the basis of the declaration of interchangeability made above.
4.4
MHLW consideration: The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5
In Canada, any of the pharmacopoeial texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES USED FOR THE Q4B EVALUATION
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum Volume 14, Number 4 (December 2005). (Note: the PDG cover letter published in this volume was subsequently changed based on Q4B comments.)
5.2
The pharmacopoeial references for Residue on Ignition/Sulphated Ash for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 5.6 (official on January 2007) (reference Sulphated Ash 01/2007:20414);
5.2.2
Japanese Pharmacopoeia (JP): 2.44 Residue on Ignition Test as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285);
5.2.3
United States Pharmacopeia (USP): <281> Residue on Ignition official in USP 29, 2nd Supplement, August 2006.
Q4B Annex 2 (R1)
EVALUATION AND RECOMMENDATION OF PHARMACOPOEIALTEXTS FOR USE IN THE ICH REGIONS ON
TEST FOR EXTRACTABLE VOLUME OF PARENTERALPREPARATIONS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Test for Extractable Volume of Parenteral Preparations General Chapter. The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.9.17. Test for Extractable Volume of Parenteral Preparations, JP 6.05 Test for Extractable Volume of Parenteral Preparations, and the section in USP <1> Injections General Chapter entitled "Volume in Containers” can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The acceptance criteria are the same in the three pharmacopoeias.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex has been implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1
General consideration: When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2
FDA consideration: Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3
EU consideration: For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter, Test for Extractable Volume of Parenteral Preparations: 2.9.17., on the basis of the declaration of interchangeability made above.
4.4
MHLW consideration: The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5
In Canada, any of the texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 13, Number 3 (August 2004).
5.2
The pharmacopoeial references for Test for Extractable Volume of Parenteral Preparations:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 5.3 (official on January 2006), Test for Extractable Volume of Parenteral Preparations (reference 01/2006:20917);
5.2.2
Japanese Pharmacopoeia (JP): 6.05 Test for Extractable Volume of Parenteral Preparations as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285);
5.2.3
United States Pharmacopeia (USP): official text published in the Revision Bulletin issued November 14, 2006, and as appeared in USP 30, 2nd Supplement, official December 1, 2007. The official text is incorporated in <1> Injections General Chapter as the section entitled "Volume in Containers".
Q4B Annex 3 (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
TEST FOR PARTICULATE CONTAMINATION:
SUB-VISIBLE PARTICLES GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Test for Particulate Contamination: Sub-Visible Particles. The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.9.19. Particulate Contamination: Sub-visible Particles, JP 6.07 Insoluble Particulate Matter Test for Injections, and USP <788> Particulate Matter in Injections can be used as interchangeable in the ICH regions subject to the following condition:
2.1.1
Instrument calibration and system suitability measurements should follow regional good manufacturing practice (GMP) requirements.
2.2 Acceptance Criteria
Except for nominal 100-milliliter (mL) parenteral products, the acceptance criteria are interchangeable. At the 100-mL nominal volume, the criteria specified in JP are more stringent than those in the other two pharmacopoeias; therefore, the criteria are not interchangeable in all three regions at that volume.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1
General consideration: When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2
FDA consideration: Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method. For nominal 100-mL parenteral products, the FDA considers testing criteria from all three pharmacopoeias as interchangeable.
4.3
EU consideration: For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter, Particulate Contamination: Sub-visible Particles: 2.9.19., on the basis of the declaration of interchangeability made above. For nominal 100-mL parenteral products, the EU considers testing criteria from all three pharmacopoeias as interchangeable.
4.4
MHLW consideration: The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5
In Canada, any of the texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
For nominal 100 mL parenteral products, Health Canada considers the testing criteria from all three pharmacopoeias to be interchangeable.
5. REFERENCES USED FOR THE Q4B EVALUATION
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 13, Number 3 (August 2004).
5.2
The pharmacopoeial references for Particulate Matter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): 5th Edition (official on January 2005) Particulate Contamination: Sub-visible Particles (reference 01/2005: 20919);
5.2.2
Japanese Pharmacopoeia (JP): 6.07 Insoluble Particulate Matter Test for Injections as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285). The method was changed in September 2007 to correct a sentence in the introduction as underlined in the text that is provided by MHLW which is appended;
5.2.3
United States Pharmacopeia (USP): <788> Particulate Matter in Injections, Revision Bulletin, April 4, 2007.
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Q4B Annex 4A (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.6.12. Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests, JP 4.05 Microbiological Examination of Non-Sterile Products: I. Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests, and USP <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The proposed texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.6.12. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 14, Number 4 (December 2005).
5.2
The pharmacopoeial references for Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): 6.3 Edition (official on January 2009) Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests (reference 01/2009: 20612);
5.2.2
Japanese Pharmacopoeia (JP): 4.05 Microbiological Examination of Non-Sterile Products: I. Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests as it appears in Supplement I to the Japanese Pharmacopoeia Fifteenth Edition (September 28, 2007, The Ministry of Health, Labour and Welfare Ministerial Notification No. 316). The English version was published on January 9, 2008;
5.2.3
United States Pharmacopeia (USP): <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests official in USP 30, January 2007.
Q4B Annex 4B (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.6.13. Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms, JP 4.05 Microbiological Examination of Non-Sterile Products: II. Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms, and USP <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The proposed texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.6.13. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 14, Number 4 (December 2005).
5.2
The pharmacopoeial references for Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): 6.3 Edition (official on January 2009) Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms (reference 01/2009: 20613);
5.2.2
Japanese Pharmacopoeia (JP): 4.05 Microbiological Examination of Non-Sterile Products: II. Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms as it appears in Supplement I to the Japanese Pharmacopoeia Fifteenth Edition (September 28, 2007, The Ministry of Health, Labour and Welfare Ministerial Notification No. 316). The English version was published on January 9, 2008;
5.2.3
United States Pharmacopeia (USP): <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms official in USP 30, January 2007.
Q4B Annex 4C (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use.
For each regulatory region, the pharmacopoeial text is non-mandatory and is provided for informational purposes only.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 5.1.4. Microbiological Quality of Non-Sterile Pharmaceutical Preparations and Substances for Pharmaceutical Use, JP General Information 12. Microbial Attributes of Non-sterile Pharmaceutical Products, and USP <1111> Microbiological Attributes of Nonsterile Pharmaceutical Products, can be used as interchangeable in the ICH regions.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 5.1.4. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the texts cited in section 2 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES USED FOR THE Q4B EVALUATION
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 14, Number 4 (December 2005).
5.2
The pharmacopoeial references for Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): 6.3 Edition (official on January 2009) Microbiological Quality of Non-Sterile Pharmaceutical Preparations and Substances for Pharmaceutical Use (reference 01/2009: 50104);
5.2.2
Japanese Pharmacopoeia (JP): JP General Information 12. Microbial Attributes of Non-sterile Pharmaceutical Products as it appears in Supplement I to the Japanese Pharmacopoeia Fifteenth Edition (September 28, 2007, Notification PFSB No. 0928001). The English version was published on January 9, 2008;
5.2.3
United States Pharmacopeia (USP): <1111> Microbiological Attributes of Nonsterile Pharmaceutical Products official in USP 30, January 2007.
Q4B Annex 5 (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Disintegration Test General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that for tablets and capsules, the official pharmacopoeial texts, Ph. Eur. 2.9.1. Disintegration of Tablets and Capsules, JP 6.09 Disintegration Test, and USP <701> Disintegration, can be used as interchangeable in the ICH regions subject to the conditions detailed below. Testing conditions for specific dosage forms are outside the scope of the harmonization of this chapter.
2.1.1
For tablets and capsules larger than 18 millimeters (mm) long for which a different apparatus is used, the Disintegration Test is not considered to be interchangeable in the three regions.
2.1.2
The Disintegration Test is not considered to be interchangeable in the three regions for dosage forms referred to in the regional compendia as delayed-release, gastro-resistant, or enteric-coated.
2.1.3
Product-specific parameters such as media and the use of discs should be specified in the application dossier.
2.2 Acceptance Criteria
Acceptance criteria are outside the scope of the harmonization of this chapter and should be specified in the application dossier.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.9.1. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the pharmacopoeial texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document (Rev. 1): Japanese Pharmacopoeial Forum, Volume 16, number 4 (December 2007).
5.2
The pharmacopoeial references for Disintegration Test General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.3 (official January 2009) Disintegration of Tablets and Capsules (reference 01/2009: 20901);
5.2.2
Japanese Pharmacopoeia (JP): 6.09 Disintegration Test as it appeared in the partial revision of the JP 15th edition made official March 31, 2009, by the Ministry of Health, Labour and Welfare Ministerial Notification No. 190;
5.2.3
United States Pharmacopeia (USP): Revision Bulletin <701> Disintegration issued June 6, 2008, and official August 1, 2008.
Q4B Annex 6
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Uniformity of Dosage Units General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph. Eur. 2.9.40. Uniformity of Dosage Units, JP 6.02 Uniformity of Dosage Units, and USP General Chapter <905> Uniformity of Dosage Units, can be used as interchangeable in the ICH regions subject to the following conditions:
2.1.1
Unless the 25 milligrams (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.
2.1.2
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.
2.1.3
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.
2.2 Acceptance Criteria
The acceptance criteria are harmonized between the three pharmacopoeias.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
FDA finds unsuitable for regulatory purposes the not more than 2% Relative Standard Deviation (RSD) exception to the 25 mg/25% threshold that appears in the JP and the Ph. Eur. Therefore, in accordance with the official text in the USP, for those items below the 25 mg/25% threshold, testing by Content Uniformity should be performed.
4.3 EU Consideration
For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.9.40. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada any of the pharmacopoeial texts cited in Section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES USED FOR THE Q4B EVALUATION
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 13, number 2 (May 2004).
5.2
The pharmacopoeial references for Uniformity of Dosage Units for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.1 (official April 2008) Uniformity of Dosage Units (reference 04/2008:20940). Further changes to the official text were made in Supplement 7.4, official April 1, 2012.
5.2.2
Japanese Pharmacopoeia (JP): 6.02 Uniformity of Dosage Units, as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285), officially updated by errata published by MHLW at http://www.pmda.go.jp/english/pharmacopoeia/pdf/ jpdata/H201105_jp15_errata.pdf on November 5, 2008. Further changes were implemented via MHLW Ministerial Notification No. 190 on May 31, 2013 (see http://www.pmda.go.jp/english/pharmacopoeia/pdf/jpdata/JP16-1en.pdf).
5.2.3
United States Pharmacopeia (USP): <905> Uniformity of Dosage Units, Pharmacopeial Forum, Volume 35, Number 3, official in USP 33-Reissue [October 2010]. USP provided notification on February 25, 2011, (see http://www.usp.org/usp-nf/harmonization/stage-6/uniformity-dosage-units) to implement requirements set forth in the 2nd paragraph of Section 4.2 of this Annex and other changes. These changes made official on December 1, 2011, concurrent with USP 34 – NF 29, 2nd Supplement.
Q4B Annex 7 (R2)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for Dissolution Test.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.9.3. Dissolution Test for Solid Dosage Forms, JP 6.10 Dissolution Test, and USP <711> Dissolution can be used as interchangeable in the ICH regions subject to the following conditions:
2.1.1
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.
2.1.2
The Dissolution Test is not considered to be interchangeable in the ICH
regions when enzymes are used in the media.
2.1.3
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.
2.1.4
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.
2.1.5
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).
2.1.6
The Dissolution Test is not considered to be interchangeable in the ICH
regions for JP Interpretation 2.
2.1.7
The Dissolution Test is not considered to be interchangeable in the ICH regions for use of large vessels (greater than 1 liter).
2.1.8
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.
2.2 Acceptance Criteria
Acceptance criteria should be specified in the application dossier.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
An appropriately rigorous mechanical calibration method, 1 when properly executed, should satisfy the current good manufacturing practice (CGMP) requirement for dissolution apparatus calibration under § 211.160(b)(4) of Title 21 of the Code of Federal Regulations.
4.3 EU Consideration
For the European Union, regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.9.3. on the basis of the declaration of interchangeability made above.
EU considers that it could accept the approach to the dissolution test for delayed-release products, as published in the USP, as meeting the criteria of the Ph. Eur. The validation studies referred to in Section 2.1.5 of this annex would normally be submitted in the marketing authorisation dossier.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
MHLW considers that it could accept the approach to the dissolution test for reciprocating cylinder apparatus as published in Ph. Eur. and USP, if the validation studies have been submitted in the marketing authorization dossier.
4.5 Health Canada Consideration
In Canada any of the pharmacopoeial texts cited in Section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
The dissolution tests for delayed-release/enteric coated products as published in the USP and in the Ph. Eur. can be considered interchangeable in Canada.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document (Rev. 2): Japanese Pharmacopoeial Forum, Volume 18, number 1 (April 2009).
5.2
The pharmacopoeial references for Dissolution Test for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.6 (official January 2010),
5.2.2
Japanese Pharmacopoeia (JP): 6.10 Dissolution Test as it appears in Supplement I to the JP Fifteenth edition (September 28, 2007, The Ministerial Notification No. 316), in the partial revision of the JP Fifteenth edition made official March 31, 2009, by the Ministry of Health, Labour and Welfare Ministerial Notification No. 190, and in the partial revision of the JP Fifteenth edition made official July 30, 2010, by the Ministry of Health, Labour and Welfare Ministerial Notification No. 322.
5.2.3
United States Pharmacopeia (USP): <711> Dissolution as presented in Pharmacopeial Forum, Volume 35(3), May/June 2009, published in USP 33-Reissue, official October 1, 2010.
Q4B Annex 8 (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Sterility Test General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, Ph. Eur. 2.6.1. Sterility, JP 4.06 Sterility Test, and USP <71> Sterility Tests, can be used as interchangeable in the ICH regions subject to the conditions detailed below. Testing conditions for medical devices, such as sutures, are outside the scope of the ICH recommendation.
2.1.1
Diluting and rinsing fluids should not have antibacterial or antifungal properties if they are to be considered suitable for dissolving, diluting, or rinsing an article under test for sterility.
2.1.2
When testing liquid parenteral preparations with a nominal volume of 100 milliliters in batches of more than 500 containers, the test is considered interchangeable if the minimum number of containers selected is either 20 or is 2 percent of the total number of containers, whichever is lower.
2.2 Acceptance Criteria
The acceptance criteria are harmonized between the three pharmacopoeias.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, the monographs of the Ph. Eur. have mandatory applicability. Regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter, Sterility: 2.6.1., on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the pharmacopoeial texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 16, number 4 (December 2007).
5.2
The pharmacopoeial references for Sterility Test for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.3 (official in January 2009), Sterility (reference 01/2009:20601);
5.2.2
Japanese Pharmacopoeia (JP): The 4.06 Sterility Test as it appeared in the partial revision of the JP 15th edition made official March 31, 2009, by the Ministry of Health, Labour and Welfare Ministerial Notification No. 190;
5.2.3
United States Pharmacopeia (USP):<71> Sterility Tests as presented in Pharmacopeial Forum, Volume 34(6), Interim Revision Announcement No. 6, December 1, 2008, official on May 1, 2009.
Q4B Annex 9 (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Tablet Friability General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the analytical procedures described in the official pharmacopoeial texts, Ph.Eur. 2.9.7. Friability of Uncoated Tablets, JP General Information 26. Tablet Friability Test, and USP <1216> Tablet Friability, can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
For interchangeability, the loss of mass for a single determination should be not more than 1.0 percent, unless otherwise specified in the dossier. When three determinations are conducted, then the mean loss of mass for the three determinations should be not more than 1.0 percent, unless otherwise specified in the dossier.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
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4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the pharmacopoeial texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 14, number 1 (March 2005).
5.2
The pharmacopoeial references for Tablet Friability General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.6 (published June 2009, official January 2010), Friability of Uncoated Tablets (reference 01/2010:20907);
5.2.2
Japanese Pharmacopoeia (JP): The JP General Information 26. Tablet Friability Test as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285), officially updated by errata published by MHLW at http://www.std.pmda.go.jp/jpPUB/Data/ENG/jpdata/H201105_jp15_errata.pdf on November 5, 2008;
5.2.3
United States Pharmacopeia (USP): <1216> Tablet Friability, official in USP 32, May 1, 2009.
Q4B Annex 10 (R1)
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
MICROBIOLOGICAL EXAMINATION OF NON-STERILE PRODUCTS:
MICROBIAL ENUMERATIONS TESTS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Polyacrylamide Gel Electrophoresis General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the official pharmacopoeial texts, the Section in Ph.Eur. 2.2.31. Electrophoresis entitled Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE), JP General Information 23. SDS-Polyacrylamide Gel Electrophoresis, and USP <1056> Biotechnology-derived Articles – Polyacrylamide Gel Electrophoresis, can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.2.31. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada, any of the pharmacopoeial texts cited in section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 9, number 1 (January 2000).
5.2
The pharmacopoeial references for Polyacrylamide Gel Electrophoresis General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): 6th Edition (official in January 2008), Electrophoresis (reference 01/2008:20231);
5.2.2
Japanese Pharmacopoeia (JP): The JP General Information 23. SDS-Polyacrylamide Gel Electrophoresis as it appears in the Japanese Pharmacopoeia Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285);
5.2.3
United States Pharmacopeia (USP): <1056> Biotechnology-derived Articles – Polyacrylamide Gel Electrophoresis official in USP 32, May 1, 2009.
Q4B Annex 11
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
CAPILLARY ELECTROPHORESIS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Capillary Electrophoresis General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the analytical procedures described in the official pharmacopoeial texts, Ph.Eur. 2.2.47. Capillary Electrophoresis, JP General Information 4. Capillary Electrophoresis, and USP General Information Chapter <1053> Biotechnology-derived Articles – Capillary Electrophoresis,1 can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.2.47. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada any of the pharmacopoeial texts cited in Section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES USED FOR THE Q4B EVALUATION
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 11, number 4 (October 2002).
5.2
The pharmacopoeial references for Capillary Electrophoresis General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.6 (published June 2009, and official January 1, 2010), Capillary Electrophoresis (reference 01/2008:20247);
5.2.2
Japanese Pharmacopoeia (JP): General Information 4. as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial Notification No. 285). The English text was officially updated by errata published by MHLW at http://www.std.pmda.go.jp/jpPUB/Data/ENG/jpdata/H201105_jp15_errata.pdf on
May 28, 2010;
5.2.3
United States Pharmacopeia (USP):2 <1053> Biotechnology-derived Articles – Capillary Electrophoresis, USP Revision Bulletin posted May 29, 2009, official July 1, 2009.
Q4B Annex 12
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
ANALYTICAL SIEVING GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Analytical Sieving General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the analytical procedures described in the official pharmacopoeial texts, Ph.Eur. 2.9.38. Particle-size Distribution Estimation by Analytical Sieving, JP 3.04 Particle Size Determination entitled Method 2. Analytical Sieving Method, and USP General Chapter <786> Particle Size Distribution Estimation by Analytical Sieving, can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.9.38. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada any of the pharmacopoeial texts cited in Section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 16, number 2 (June 2007).
5.2
The pharmacopoeial references for the Analytical Sieving General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.2 (published December 11, 2007, and official July 2008), Particle-size Distribution Estimation by Analytical Sieving (reference 07/2008:20938);
5.2.2
Japanese Pharmacopoeia (JP): 3.04 Particle Size Determination as it appeared in Supplement II to the JP Fifteenth Edition (September 30, 2009, The Ministerial Notification No. 425). The English version of the JP text was published June 4, 2010, and is available at www.std.pmda.go.jp/jpPUB/index_e.html;
5.2.3
United States Pharmacopeia (USP): <786> Particle Size Distribution Estimation by Analytical Sieving, USP 32 Supplement 2 (official 12/1/09), and Errata in Interim Revision Announcement to USP 32 appearing in Pharmacopeial Forum, Vol. 35, no. 5, released September 1, 2009, and official October 1, 2009.
Q4B Annex 13
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
BULK DENSITY AND TAPPED DENSITY OF POWDERS GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Bulk Density and Tapped Density of Powders General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the analytical procedures described in the official pharmacopoeial texts, Ph.Eur. 2.9.34. Bulk Density and Tapped Density of Powders, JP 3.01 Determination of Bulk and Tapped Densities, and USP General Chapter <616> Bulk Density and Tapped Density of Powders, can be used as interchangeable in the ICH regions.
2.2 Acceptance Criteria
The texts evaluated did not contain acceptance criteria.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.9.34. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada any of the texts cited in Section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document (Rev. 1 – Corr. 1): Japanese Pharmacopoeial Forum, Volume 18, number 3 (September 2009).
5.2
The pharmacopoeial references for the Bulk Density and Tapped Density of Powders General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.8 to Ph.Eur. 6th Edition (official July 2010), Bulk Density and Tapped Density of Powders (reference 07/2010:20934).
5.2.2
Japanese Pharmacopoeia (JP): 3.01 Determination of Bulk and Tapped Densities as it appears in the JP Sixteenth Edition (March 24, 2011, The Ministry of Health, Labour and Welfare Ministerial Notification No. 65).
5.2.3
United States Pharmacopeia (USP): <616> Bulk Density and Tapped Density of Powders, USP 34, 2nd Supplement official December 1, 2011).
Q4B Annex 14
Evaluation and Recommendation of Pharmacopoeial Text for Use in the ICH Regions on
BACTERIAL ENDOTOXINS TEST GENERAL CHAPTER
1. INTRODUCTION
This annex is the result of the Q4B process for the Bacterial Endotoxins Test General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
2. Q4B OUTCOME
2.1 Analytical Procedures
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group (EWG), recommends that the analytical procedures described in the official pharmacopoeial texts, Ph.Eur. 2.6.14. Bacterial Endotoxins, JP 4.01 Bacterial Endotoxins Test, and USP General Chapter <85> Bacterial Endotoxins Test, can be used as interchangeable in the ICH regions subject to the following conditions:
2.1.1
Any of the three 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.
2.1.2
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.
2.1.3
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.
2.2 Acceptance Criteria
The evaluated texts did not contain acceptance criteria. Endotoxin limits should be specified in the application dossier unless otherwise specified in an individual monograph.
3. TIMING OF ANNEX IMPLEMENTATION
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a region, it can be used in that region. Timing might differ for each region.
4. CONSIDERATIONS FOR IMPLEMENTATION
4.1 General Consideration
When sponsors or manufacturers change their existing methods to the implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, any change notification, variation, and/or prior approval procedures should be handled in accordance with established regional regulatory mechanisms pertaining to compendial changes.
4.2 FDA Consideration
Based on the recommendation above, and with reference to the conditions set forth in this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be considered interchangeable. However, FDA might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.
4.3 EU Consideration
For the European Union, regulatory authorities can accept the reference in a marketing authorisation application, renewal or variation application citing the use of the corresponding text from another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter 2.6.14. on the basis of the declaration of interchangeability made above.
4.4 MHLW Consideration
The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as interchangeable in accordance with the conditions set out in this annex. Details of implementation requirements will be provided in the notification by MHLW when this annex is implemented.
4.5 Health Canada Consideration
In Canada any of the pharmacopoeial texts cited in Section 2.1 of this annex and used in accordance with the conditions set out in this annex can be considered interchangeable.
5. REFERENCES
5.1
The PDG Stage 5B sign-off document (Rev. 1 – Correction 1): Japanese Pharmacopoeial Forum, Volume 18, number 4 (December 2009).
5.2
The pharmacopoeial references for the Bacterial Endotoxins Test General Chapter for this annex are:
5.2.1
European Pharmacopoeia (Ph. Eur.): Supplement 6.6 (official January 1, 2010), Bacterial Endotoxins (reference 01/2010:20614).
5.2.2
Japanese Pharmacopoeia (JP): General Test 4.01 Bacterial Endotoxins Test as it appears in the JP Sixteenth Edition (March 24, 2011, The Ministry of Health, Labour and Welfare Ministerial Notification No.65).
5.2.3
United States Pharmacopeia (USP): Text for <85> Bacterial Endotoxins Test, USP 33 Reissue (published April 2010 and official October 1, 2010).
