12 December 2024

EMA/CHMP/ICH/222007/2006
Committee for Human Medicinal Products

ICH Q4B(R1) Guideline on evaluation and

recommendation of pharmacopoeial texts for use in the
ICH regions
Step 5

Release for information 18 December 2024

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Document history

Code * History Date

Q4B Approval by the Steering Committee under Step 2 and 8 June 2006
release for public consultation.
Q4B Approval by the Steering Committee under Step 4 and 1 November 2007
recommendation for adoption to the three ICH regulatory
bodies.

Current Step 4 version

Q4B(R1) Revised by the PDG following endorsement of the 5 June 2024

maintenance procedure to reflect that responsibility for
the maintenance of Q4B and its annexes was handed
over to the PDG. Process and individual
interchangeability statements taken out and transferred
to the ICH SOP or specific Q4B annexes.

ICH Q4B(R1) Guideline on evaluation and recommendation of pharmacopoeial texts for

use in the ICH regions
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Q4B(R1) Guideline on evaluation and recommendation of
pharmacopoeial texts for use in the ICH regions
Table of contents
1. Introduction ....................................................................................................................... 4
1.1. Objective(s) of the guideline ............................................................................................. 4
1.2. Background .................................................................................................................... 4
1.2.1. The pharmacopoeial discussion group ........................................................................... 4
1.2.2. The Q4B expert working group (EWG) .......................................................................... 4
1.2.3. Extension of the Q4B maintenance procedure to non-PDG pharmacopoeias. ...................... 5
2. Guidelines .......................................................................................................................... 5
2.1. Scope............................................................................................................................. 5
2.2. Q4B Maintenance process ................................................................................................. 5
2.3. Annex contents ............................................................................................................... 5
2.4. Use of the pharmacopoeial text ......................................................................................... 5
2.4.1. Considerations for implementation ............................................................................... 5
3. Glossary ............................................................................................................................. 6
Attachment I: List of general test chapters within the scope of the ICH Q4B guideline ......... 7

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1. Introduction
1.1. Objective(s) of the guideline

This document describes the process for the evaluation and recommendation of selected
pharmacopoeial texts to facilitate their recognition by regulatory authorities for use as interchangeable
by the ICH regulatory members.

This process was initially under the responsibility of the ICH Q4B Expert Working Group (EWG) until it
was disbanded at the end of 2010. The Pharmacopoeial Discussion Group (PDG) took over this
responsibility in November 2018.

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 had recognised that full use and value
of both ICH Guidelines would depend on the successful harmonisation of pharmacopoeial procedures
and encouraged the work of the PDG.

1.2.1. The pharmacopoeial discussion group

The PDG, founded in 1989, consists of representatives from the European Directorate for the Quality of
Medicines and HealthCare (EDQM) of the Council of Europe; the Ministry of Health, Labour and Welfare
(MHLW) of Japan; and the United States Pharmacopoeial Convention (USP). Since 2001, WHO has
been an observer to the PDG. The Indian Pharmacopeia Commission (IPC) has participated in an
expansion pilot of PDG since October 2022 and has been welcomed as a member of PDG in October
2023.

In November 2018, ICH and the PDG agreed to collaborate on the maintenance of the current ICH Q4B
Annexes, following the maintenance procedure described in Annex 5 of the Standard Operating
Procedure of the ICH Working Groups. At the June 2023 ICH meeting in Vancouver, the ICH Assembly
endorsed the maintenance procedure proposed by PDG.

1.2.2. The Q4B expert working group (EWG)

In November 2003, ICH had established the Q4B EWG to evaluate and recommend pharmacopoeial
texts to be proposed for interchangeable use in the three founding ICH regions (USA, European Union,
Japan).

The Q4B EWG had evaluated pharmacopoeial text proposals and assessed their regulatory impact.
Following its evaluation, the Q4B EWG had made a recommendation on the interchangeable use of the
text in the founding ICH regions which had been transmitted to the ICH Steering Committee. For each
proposal that had been favourably evaluated, the Q4B EWG had developed a topic-specific annex to
the Q4B Guideline. The annex provided information on how the pharmacopoeial texts can be used in
the founding ICH regions. Each annex was issued as a stand-alone companion document to the Q4B
guideline.

The Annexes were subsequently revised to include the interchangeability statement from Health
Canada.

After completion of the evaluation of the regulatory interchangeability of 16 General Test Chapters,
resulting in 16 Q4B Annexes, the Q4B EWG was disbanded, in 2010.

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1.2.3. Extension of the Q4B maintenance procedure to non-PDG pharmacopoeias.

Since 2010, new regulatory members, some of which have a pharmacopoeia, have joined ICH.
Therefore, careful consideration of the impact of the maintenance of the Q4B Annexes on those
regulatory members (and their pharmacopoeias) as well as of the impact of the General Test Chapters
of those pharmacopoeias on the Q4B Annexes is essential.

To take into consideration this increased membership, a new maintenance procedure had been
proposed by the PDG to the ICH Assembly and approved by the latter. This procedure is described in
Annex 5 of the Standard Operating Procedure of the ICH Working Groups.

2. Guidelines
2.1. Scope

The Q4B process focuses on evaluating and maintaining the 16 Q4B Annexes referred to in Attachment
I.

2.2. Q4B Maintenance process

The process is described in Annex 5 of the Standard Operating Procedure of the ICH Working Groups.

2.3. Annex contents

The Q4B annexes 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

2.4. Use of the pharmacopoeial text

After a regulatory ICH member has implemented the Q4B annex, the official pharmacopoeial texts
referenced in the annex can be used as interchangeable in accordance with the member’s legal
framework. The pharmacopoeial references used for the PDG review are specified in the Q4B annexes.
However, it is recommended to refer to the current official pharmacopoeial texts when using the
annexes. Any general and/or specific implementation recommendations for a regulatory member 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:

2.4.1. 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

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change notification, variation, and/or prior approval procedures should be handled in accordance with
established national/regional regulatory mechanisms pertaining to compendial changes.

In addition to these general considerations, implementation status for each regulatory member is
provided in each annex and specific information for each regulatory member is also provided to assist
the implementation in that country/region. Each regulatory member will provide such notification to its
stakeholders in conjunction with regional implementation of the annex.

3. Glossary
Interchangeable – Where such status is indicated, any of the official texts from JP, Ph. Eur., USP or
from the other pharmacopoeias referenced in the Q4B Annex can be substituted one for the other
(appropriately referenced) in the ICH countries/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 pharmacopoeia referenced in the Q4B Annex is
used.

Q4B Outcome – Produced by the Q4B evaluation; 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.

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Attachment I: List of general test chapters within the scope
of the ICH Q4B guideline
List of general test chapters within the scope of the ICH Q4B guideline

Residue on Ignition/Sulphated Ash

Extractable Volume

Particulate Contamination: Sub-visible particles

Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests

Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms

Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical

Preparations and Substances for Pharmaceutical Use
Disintegration

Uniformity of Dosage Units

Dissolution

Sterility Test

Tablet Friability

Polyacrylamide Gel Electrophoresis

Capillary Electrophoresis

Analytical Sieving

Bulk Density of Powders

Bacterial Endotoxins

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