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M4S – The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Safety
Guideline number: M4S(R2)
Status: Implementation (Step 5)
Adopted (Step 4): 20 December 2002
Nonclinical Summaries and Organisation of Module 4
Re-edited with Numbering and Section Headers changes, September 2002.
The CTD Safety (M4S) Guideline delineates the structure and format of the nonclinical summaries in Module 2 of the Common Technical Document, and provides the organisation of Module 4, the Nonclinical Study Reports. The Nonclinical Overview should present an integrated and critical assessment of the pharmacologic, pharmacokinetic, and toxicologic evaluation of the pharmaceutical, and generally should not exceed 30 pages. The Nonclinical Written Summaries (100 – 150 pages) are recommended to provide more extensive summaries and discussion of the nonclinical information on pharmacology, pharmacokinetics and toxicology. Thirty-four templates are provided for the preparation of the Nonclinical Tabulated Summaries, and 31 example tables are provided. Finally, the organisation of the Nonclinical Study Reports in Module 4 is described. Preparation of the nonclinical sections of the Common Technical Document according to the M4S Guideline results in a single Harmonised dossier of the nonclinical information that is acceptable in all ICH regions.
Please note that a small typing mistake has been corrected on page 46. Read point 2.6.7.3 Toxicokinetics (instead of 2.7.7.3).
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).
Q+A
Q+A number: M4S Q&As (R2)
Q+A Status: Implementation (Step 5)
Q+A Adopted (Step X): 11 November 2003
Q+A implementation
In order to facilitate the implementation of the CTD Safety (M4S) Guideline, the ICH Experts have developed a series of Q&As. The document reached Step 4 of the ICH Process in November 2003.
