ICH Harmonised Tripartite Guideline - Safety - M4S(R2) - Nonclinical Overview and Nonclinical Summaries of Module 2, Organisation of Module 4 - Current Step 4 version

Oct 4, 2026

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ICH Harmonised Tripartite Guideline M4S(R2) defines Safety-focused requirements for the Common Technical Document used in the registration of pharmaceuticals for human use. The guideline details how Module 2 nonclinical overview and nonclinical summaries should be organized, presented, and structured within the CTD framework, including written and tabulated summaries. It specifies section-level content expectations and formatting principles for key subtopics such as general aspects, pharmacology summaries, pharmacokinetics summaries, and supporting tables and figures under the current Step 4 version.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages115

Reading Time4 h 50 min

AccessFree to download

MODULE 2 : COMMON TECHNICAL DOCUMENT SUMMARIES

General Principles of Nonclinical Overview and Summaries

2.4 NONCLINICAL OVERVIEW

General Aspects

Content and Structural Format

2.6 NONCLINICAL WRITTEN AND TABULATED SUMMARIES

Nonclinical Written Summaries

Introduction

General Presentation Issues

2.6.1 Introduction

2.6.2 Pharmacology Written Summary

2.6.2.1 Brief Summary

2.6.2.2 Primary Pharmacodynamics

2.6.2.3 Secondary Pharmacodynamics

2.6.2.4 Safety Pharmacology

2.6.2.5 Pharmacodynamic Drug Interactions

2.6.2.6 Discussion and Conclusions

2.6.2.7 Tables and Figures

2.6.3 Pharmacology Tabulated Summary (see Appendix B)

2.6.4 Pharmacokinetics Written Summary

2.6.4.1 Brief Summary

2.6.4.2 Methods of Analysis

2.6.4.3 Absorption

2.6.4.4 Distribution

2.6.4.5 Metabolism (interspecies comparison)

2.6.4.6 Excretion

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE THE COMMON TECHNICAL DOCUMENT FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE: SAFETY – M4S(R2) NONCLINICAL OVERVIEW AND NONCLINICAL SUMMARIES OF MODULE 2 ORGANISATION OF MODULE 4 Current Step 4 version dated 20 December 2002 This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA. M4S(R2) Document History | First
Codification | History | Date | New
Codification
November
2005 | | --- | --- | --- | --- | | M4S | Approval by the Steering Committee under Step 2 and release for public consultation. | 20
July
2000 | M4S | | --- | --- | --- | --- | | M4S | Approval by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies. | 8
November
2000 | M4S | | M4S | Approval by the Steering Committee of Numbering and Section Headers changes for consistency directly under Step 4 without further public consultation. | 12
September
2002 | M4S(R1) | Current Step 4 version | M4S | Approval by the Steering Committee of a minor editorial correction. | 20
December
2002 | M4S(R2) | | --- | --- | --- | --- | In order to facilitate the implementation of the M4S guideline, the ICH Experts have developed a series of Q&As which can be downloaded from the ICH web site: [http://www.ich.org](http://www.ich.org) M4S Questions & Answers History | M4S Q&As | Approval by the Steering Committee. | 24
May
2001 | M4S Q&As | | --- | --- | --- | --- | | M4S Q&As | Approval by the Steering Committee of the newly added questions. | 12
September
2002 | M4S Q&As
(R1) | | M4S Q&As | Approval by the Steering Committee of the newly added questions. | 6
February
2003 | M4S Q&As
(R2) | | M4S Q&As | Approval by the Steering Committee of the newly added questions. | 18
July
2003 | M4S Q&As
(R3) | Current M4S Questions & Answers posted on the web site | M4S Q&As | Approval by the Steering Committee of the newly added questions. | 11
November
2003 | M4S Q&As
(R4) | | --- | --- | --- | --- | THE COMMON TECHNICAL DOCUMENT FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE: SAFETY NONCLINICAL OVERVIEW AND NONCLINICAL SUMMARIES OF MODULE 2 ORGANISATION OF MODULE 4 ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 9 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICH (Numbering and Section Headers have been edited for consistency and use in e-CTD as agreed at the Washington DC Meeting, September 11-12, 2002) (This document includes the typographic correction on page 46 : to read point [2.6.7.3](2.6.7.3), agreed by the Steering Committee on 20 December 2002). TABLE OF CONTENTS MODULE 2 : COMMON TECHNICAL DOCUMENT SUMMARIES .................... 1 General Principles of Nonclinical Overview and Summaries............................................ 1 2.4 NONCLINICAL OVERVIEW ................................................................................ 1 General Aspects .......................................................................................................... 1 Content and Structural Format .......................................................................................... 2 2.6 NONCLINICAL WRITTEN AND TABULATED SUMMARIES ...................... 3 Nonclinical Written Summaries .......................................................................................... 3 Introduction.......................................................................

FAQs

What does ICH M4S(R2) cover in the CTD safety section?

It covers the nonclinical overview and nonclinical summaries required for Module 2, including how written and tabulated summaries should be organized and presented for pharmaceutical registration safety evaluation.

Which parts of the nonclinical overview and summaries are specified in the table of contents?

The guideline specifies General Principles, 2.4 Nonclinical Overview (General Aspects and Content/Structural Format), and 2.6 Nonclinical Written and Tabulated Summaries, including pharmacology and pharmacokinetics sub-sections.

What approval context and version information is provided for M4S(R2)?

The document states it reached Step 4 of the ICH Process, includes a current Step 4 version dated 20 December 2002, and notes approvals by the ICH Steering Committee for adoption to the three regulatory parties.

Oct 4, 2026

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