S2 – Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use

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The ICH Harmonised Guideline was finalised under Step 4 in November 2011. It replaces and combines the ICH S2A and S2B Guidelines.

The S2A Guideline on Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals was finalised under Step 4 in July 1995. This document provided specific guidance and recommendations for in vitro and in vivo tests and on the evaluation of test results. It includes a glossary of terms related to genotoxicity tests to improve consistency in applications.

The S2B Guideline on Genotoxicity: A Standard Battery for Genotoxicity Testing for Pharmaceuticals was finalised under Step 4 in July 1997. This document addressed two fundamental areas of genotoxicity testing: the identification of a standard set of assays to be conducted for registration, and the extent of confirmatory experimentation in any particular genotoxicity assay in the standard battery. The purpose of the revision is to optimise the standard genetic toxicology battery for prediction of potential human risks, and to provide guidance on interpretation of results, with the ultimate goal of improving risk characterisation for carcinogenic effects that have their basis in changes in the genetic material. The revised guidance describes internationally agreed upon standards for follow-up testing and interpretation of positive results in vitro and in vivo in the standard genetic toxicology battery, including assessment of non-relevant findings.

The ICH Harmonised Guideline was finalised under Step 4 in July 1997. This document covers the preclinical safety testing requirements for biotechnological products. It addresses the use of animal models of disease, determination of when genotoxicity assays and carcinogenicity studies should be performed, and the impact of antibody formation on duration of toxicology studies.

An addendum was proposed to provide clarification on S6 and an update of the following topics discussed in the original ICH S6 Guideline: species selection, study design, immunogenicity, reproductive and developmental toxicity and assessment of carcinogenic potential. The Harmonised addendum provides further complementary guidance to the S6 Guideline and helps to define the current recommendations and reduce the likelihood that substantial differences will exist among regions.

The addendum reached Step 4 of the harmonisation process in June 2011 and was integrated as part II in the core Guideline that was then renamed S6(R1).

Annexes

No results found.

Guideline implementation

ANMAT, Argentina

Not yet implemented;

ANVISA, Brazil

Implemented; Date: 1 January 2013; Reference: Guideline for Toxicological Non-Clinical Studies and Pharmacological Safety required for the development of medicines

COFEPRIS, Mexico

Implemented; Date: 9 October 2024; Reference: Guideline on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use

EC, Europe

Implemented; Date: 1 June 2012; Reference: CHMP/ICH/126642/2008

EDA, Egypt

Implemented; Date: 1 January 2011; Reference: Regulatory Guide for mechanisms, procedures and rules of implementing the Decree of Egyptian Drug Authority No.343 of 2021

FDA, United States

Implemented; Date: 1 June 2012; Reference: Vol. 77, No. 110, p. 33748-9

HSA, Singapore

Implemented; Date: 1 November 2011; Reference: HSA, Singapore webpage: Guidance documents for clinical trials

Health Canada, Canada

Implemented; Date: 21 January 2016; Reference: File #: 15-114028-981

JFDA, Jordan

Implemented;

MFDS, Republic of Korea

Implemented; Date: 30 August 2017; Reference: Standard for Toxicity Study of Pharmaceuticals, etc. [MFDS, Republic of Korea Notification]

MHLW/PMDA, Japan

Implemented; Date: 1 December 2012; Reference: PFSB/ELD Notification No. 0920-2

MHRA, UK

Implemented; Date: 18 December 1995;

NAFDAC, Nigeria

Not yet implemented;

NMPA, China

Implemented; Date: 1 May 2020; Reference: NMPA, China Announcement No. 89 (2019)

SAHPRA, South Africa

In the process of implementation;

SFDA, Saudi Arabia

Implemented; Date: 7 January 2024;

Swissmedic, Switzerland

Implemented; Date: 9 November 2011; Reference: Swissmedic, Switzerland press release

TFDA, Chinese Taipei

Implemented; Date: 7 July 2014; Reference: 1. Guidance on Pharmacetutical Non-clinical Safety V5 2. Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use

TITCK, Türkiye

Implemented; Date: 6 October 2020; Reference: Guideline on Non-Clinical Evaluation of Human Vaccines 6.10.2020