The CTD triangle. Click to view PDF.
The CTD triangle. Click to view PDF.

M4 : The Common Technical Document

The agreement to assemble all the Quality, Safety and Efficacy information in a common format (called CTD - Common Technical Document ) has revolutionised the regulatory review processes, led to harmonised electronic submission that, in turn, enabled implementation of good review practices. For industries, it has eliminated the need to reformat the information for submission to the different ICH regulatory authorities.

The CTD is organised into five modules. Module 1 is region specific and Modules 2, 3, 4 and 5 are intended to be common for all regions. In July 2003, the CTD became the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA.

More information: An electronic version of the Common Technical Document (eCTD) can be produced using the information developed by the eCTD Implementation Working Group.

  • M4(R3): Organisation

    Finalised Guideline: September 2002

    M4 (R3): Organisation Including the Granularity document that provides guidance on document location and paginations.

    The overall organisation of the CTD is presented here.

    The CTD is organised into five modules:

    Module1 is for administrative information and prescribing information, and should contain documents that are specific to each region; for example, application forms or the proposed label for use in the region. Module 2 contains the CTD summaries and should begin with a general introduction to the drug, including its pharmacological class, mode of action and proposed clinical use. Module 2 should also provide the overall summary of the ‘quality’ information provided, the non-clinical overview and the clinical overview, as well as the non-clinical written summaries and the tabulated summaries, and the clinical summary. As a foundation for the aforementioned material, module 3 contains information on quality topics, module 4 contains the nonclinical study reports and module 5 contains the clinical study reports.
    The organisation of summaries in module 2 is described in Guidelines for M4Q, M4S, M4E.

    The Common Technical Document was agreed upon in November 2000 and re-edited with Numbering and Section Headers changes, September 2002.

    Implementation:

    Step 5

    EU:

    Adopted by CPMP, November 2003, issued as CPMP/ICH/2887/99 rev.2 Organisation CTD (including the revised Granularity)

    MHLW:

    Adopted 25 May 2004, PFSB/ELD Notification No. 0525003 (including the revised Granularity)

    FDA:

    Posted on the FDA website 18 Ocober 2005

    M4 Q&As Document (R3)

    Finalised Q&As:
    June 2004

    In order to help users deal with issues which may arise during attempts to use the CTD, the ICH has supplied a Questions & Answers section on the ICH web site to answer most, if not all, questions anyone may have. If issues arise that are not answered on the web site, additional questions can be submitted for a formal response.

    Implementation:

    Step 5

    EU:

    Released for information as CHMP/ICH/5552/02, June 2004.

    MHLW:

    Adopted 24 November 2004, PFSB/ELD Notification

    FDA:

    Posted on the FDA website 22 December 2004

  • M4Q(R1): Quality

    Finalised Guideline: September 2002

    Module 2 : Quality Overall Summary (QOS)

    Module 3 : Quality

    The section of the application covering chemical and pharmaceutical data including data for biological/ biotechnological products.

    Re-edited with Numbering and Section Headers changes, September 2002

    The Quality section of the Common Technical Document (M4Q) provides a harmonised structure and format for presenting CMC (Chemistry, Manufacturing and Controls) information in a registration dossier. The table of contents includes sections on Drug Substance and Drug Product. There are also sections for regional specific information as well as some appendices. Due to the fact that many CMC topics have not yet been the subject of ICH guidelines (e.g. drug substance synthesis, drug product manufacture, container closure), the content of M4Q is not totally harmonised. A new section on Pharmaceutical Development has been included to replace the Development Pharmaceutics Report (currently a part of the EU submission requirements). Also, a new CMC summary document, the Quality Overall Summary, has been developed.

    Implementation:

    Step 5

    EU:

    Adopted by CPMP, March 2003, issued as CPMP/ICH/2887/99 rev.1 Quality

    MHLW:

    Adopted on July 1, 2003, PFSB/ELD Notification No. 0701004

    FDA:

    To be notified

    M4Q Q&As Document (R1)

    Finalised Q&As:
    July 2003

    Implementation:

    Step 5

    EU:

    Adopted by CPMP, August 2003, issued as Location Issues Quality CPMP/ICH/4680/02

    MHLW:

    Questions and Answers / Location Issues adopted on 5 November 2003, PFSB/ELD Notification

    FDA:

    Quality Questions and Answers /Location Issues (Issued 6/2004, Posted 6/8/2004) on FDA website

  • M4S(R2): Safety

    Finalised Guideline: September 2002

    Nonclinical Summaries and Organisation of Module 4

    The non-clinical section of the application.

    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 Nonclincal 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 three 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)

    Implementation:

    Step 5

    EU:

    Adopted by CPMP, March 2003, issued as CPMP/ICH/2887/99 rev.1 Safety

    MHLW:

    Adopted on July 1, 2003, PFSB/ELD Notification No. 0701004

    FDA:

    To be notified

    M4S Q&As Document (R2)

    Finalised Q&As: November 2003

    Implementation:

    Step 5

    EU:

    Q&As Adopted by CPMP, 20 November 2003, issued as CPMP/ICH/5549/02

    MHLW:

    Adopted May 24, 2004, PFSB/ELD Notification

    FDA:

    To be notified

  • M4E(R1): Efficacy

    Finalised Guideline: September 2002

    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.

    Implementation:

    Step 5

    EU:

    Adopted by CPMP, March 2003, issued as CPMP/ICH/2887/99 rev.1 Safety

    MHLW:

    Adopted on July 1, 2003, PFSB/ELD Notification No. 0701004

    FDA:

    To be notified

    M4E Q&As Document (R1)

    Finalised Q&As:
    June 2004

    Implementation:

    Step 5

    EU:

    Released for information as CHMP/ICH/5551/02, June 2004.

    MHLW:

    Adopted 24 November 2004, PFSB/ELD Notification

    FDA:

    Posted on the FDA website, September 12, 2006
    Clarification for Q&A 10 on submitting integrated summaries of safety and effectiveness (ISS/ISE) in the eCTD format (esrs/eCTD page). http://www.fda.gov/cder/regulatory/ersr/ISS_ISE_clarification.htm