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M4E – The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Efficacy
Guideline number: M4E(R2)
Status: Implementation (Step 5)
Adopted (Step 4): 15 June 2016
Module 2: Clinical Overview and Clinical Summary
Module 5: Clinical Study Reports. The clinical section of the Application.
Re-edited with Numbering and Section Headers changes, September 2002.
CTD Efficacy (M4E) describes the structure and format of the clinical data in an application, including summaries and detailed study reports. There are two high level clinical summaries in Module 2 of the CTD: the Clinical Overview, a short document that provides a critical assessment of the clinical data; and the Clinical Summary, a longer document that focuses on data summarisation and integration. Clinical Study Reports and raw data (where applicable) are included in Module 5 of the CTD.
The revised version of the ICH M4E(R1) Guideline on Enhancing the Format and Structure of Benefit-Risk Information in ICH, was approved by the Assembly under Step 4 of the ICH Process at the Lisbon meeting in June 2016. The M4E(R2) Guideline includes greater specificity on the format and structure of benefit-risk information, harmonising the presentation of this information in regulatory submissions. The document proposes a review and revision in some parts of the Section 2.5 Clinical Overview of the Module 2 of the Common Technical Document (CTD) (Section 2.5.1 and 2.5.6) to ensure the guideline is both Harmonised and sensible in its entirety.
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: M4E Q&As (R4)
Q+A Status: Implementation (Step 5)
Q+A Adopted (Step X): 10 June 2004
Q+A implementation
In order to facilitate the implementation of the CTD Efficacy (M4E) Guideline, the ICH Experts have developed a series of Q&As. The document reached Step 4 of the ICH Process in June 2004.
