CTD New Codification as per November 2005

In November 2005, the ICH Steering Committee adopted a new codification system for ICH Guidelines. The purpose of this new codification is to ensure that the numbering / coding of ICH Guidelines is more logical, consistent and clear. Because the new system applies to existing as well as new ICH Guidelines a history box has been added to the beginning of all Guidelines to explain how the Guideline was developed and what is the latest version. With the new codification revisions to an ICH Guideline are shown as (R1), (R2), (R3) depending on the number of revisions. Annexes or Addenda to Guidelines have now been incorporated into the core Guidelines and are indicated as revisions to the core Guideline (e.g., R1). For implementation reasons, the Regulatory Authorities working within the ICH Regions (European Commission, Food and Drug Administration and Ministry of Health, Labor and Welfare) may not change the codification retrospectively. The tables below are intended to clarify the old/new ICH Guidelines codification, with effect November 2005.

M4 : The Common Technical Document

The compiled text of the draft Common Technical Document reached Step 2 of the ICH process at the Steering Committee Meeting in July 2000. The full draft Common Technical Document was released for public consultation, with the deadline for comments for the end of September 2000. A final Common Technical Document was completed in November 2000. 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.

The Common Technical Document is divided into 5 Sections :

Organisation / General

Quality Safety Efficacy Electronic

More information on the CTD :

CTD Links (including the Regional Questions & Answers) CTD General Information (powerpoint slides), June 13, 2002

Status of the Common Technical Document Guidelines

Ask the ICH Secretariat for a CD-ROM containing the Word documents, or the printed (A4 paper) Guidelines. The order form here. (Handling costs are charged), or : Download here the CTD Guidelines

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

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

The Common Technical Document provides for a harmonised structure and format for new product applications. The Common Technical Document was agreed upon in November 2000, in

San Diego, USA. This Common Technical Document is divided into four separate sections. The four sections address the application organisation (M4 : Organisation), the Quality section (M4Q), the Safety section (M4S) and the Efficacy section (M4E) of the harmonised application. The agreed upon implementation date for the Common Technical Document in the three regions was July 2003.

M4 (R3) Organisation With Revised Annex: Granularity Document November 2003 The Annex has been corrected on January 13, 2004 (as per detail on page 1). The M4 General Questions & Answers (R3)

Implementation (Step 5) of the re-edited version : EU : Adopted by CPMP, November 2003, issued as CPMP/ICH/2887/99 rev.2 Organisation CTD (including the revised Granularity) MHLW : Adopted May 25, 2004, PFSB/ELD Notification n. 0525003 (including the revised Granularity) FDA : The revised M4 Granularity Annex is available from: http://www.fda.gov/cder/guidance/7042fnl.pdf

Status : Step 5 September 2002

Implementation (Step 5) status of the June 2004 version : 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 at http://www.fda.gov/cder/guidance/6674fnl.pdf, December 22, 2004

Status : Step 5 June 2004

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M4Q (R1): Quality 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. M4Q (R1) Implementation (Step 5) of the Re-edited version : 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 Implementation (Step 5) of the July 2003 version : 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 [Word] or [PDF] or [HTML] (Issued 6/2004, Posted 6/8/2004) http://www.fda.gov/cder/guidance/5951fnl.pdf Status : Step 5 September 2002

The M4 Quality Questions & Answers (R1)

Status : Step 5 July 2003

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M4S (R2) SAFETY 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) M4S (R2) Implementation (Step 5) of the Re-edited version : 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 Implementation (Step 5) status of the November 2003 version : Status : Step 5 September 2002

The M4 Safety Questions EU: Adopted by CPMP, 20 November 2003, issued as & Answers (R4) CPMP/ICH/5549/02 MHLW: Adopted May 24, 2004, PFSB/ELD Notification FDA: To be notified Back to top

Status : Step 5 November 2003

M4E (R1): EFFICACY 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. M4E (R1) Implementation (Step 5) of the Re-edited version : EU: Adopted by CPMP, March 2003, issued as CPMP/ICH/2887/99 rev.1 Efficacy MHLW: Adopted on July 1, 2003, PFSB/ELD Notification No. 0701004 Status : Step 5 September 2002

The M4 Efficacy Questions & Answers (R4)

FDA: To be notified Implementation (Step 5) status of the June 2004 version : 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 at http://www.fda.gov/cder/guidance/6673fnl.pdf December 22, 2004 NEW ! : 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

Status :Step 5 June 2004

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eCTD The electronic CTD This specification has been developed by the ICH M2 Expert Working Group and maintained by the eCTD Implementation Working Group in accordance with the ICH Process as pertains to the M2 EWG and eCTD change control as it pertains to the eCTD IWG. eCTD Specs.v.3.2 Implementation (Step 5): Status : Step 5 November 2003 EU: Published on the EMEA eSubmission website MHLW: Adopted May 27, 2004, PFSB/ELD Notification n 0527001 FDA: Posted on the FDA website at http://www.fda.gov/cder/guidance/6339fnl.pdf March 14, 2005 Open the complete eCTD page from here