The Common Technical Document

The common technical document (CTD) is a method of submitting an NDA. It is a very useful outcome of ICH discussions regarding the creation and implementation of standardized document formats. While individual regulatory agencies still have different requirements of specific content of various documents, this standardized format is a considerable step forward in the harmonization of submissions to multiple agencies. This guideline, adopted by the ICH regions (Europe, Japan, and the United States) in 2000, has subsequently been implemented, and other countries may continue to adopt it. 

The CTD consists of five modules, although it must be noted that module 1 is technically not part of the CTD since it is region specific and may contain quite different information from one regulatory submission to another. Module 2 contains a brief general introduction and summary information addressing manufacturing issues (quality) and the safety and efficacy of the drug. Module 3 contains information on quality, and modules 4 and 5 contain individual study reports for nonclinical studies and clinical studies, respectively. 

A further development related to the CTD is the move toward submitting it electronically, a submission format called e-CTD that was initiated through the ICH. In this format, information is contained in individual files that are associated with a backbone. In this way, information that is submitted as part of one application can be used in another application simply by providing information concerning where it is located in the sponsor s accumulating database. The FDA actively encourages NDA submission in the e-CTD format. ICH Guideline M4, The CTD, provides more information on this submission format. 

New Drug Development Design, Methodology and Analysis. By J. Rick Turner Copyright 2007 John Wiley Sons, Inc. 

Biopharmaceuticals comprise another very important category of molecules that have beneficial therapeutic properties. Biopharmaceuticals will be considered separately for several reasons. First, the drug discovery process is different. Second, there are important differences in the pharmacokinetics and pharmacodynamic properties of traditional small-molecule drugs and biopharmaceuticals. While general pharmacokinetic and pharmacodynamic principles apply equally to small-molecule drugs and biopharmaceutical drugs, biopharmaceuticals often exhibit unique pharmacokinetic and pharmacodynamic properties (Meibohm, 2006). Discussion of biopharmaceuticals starts in Section 3.6. 

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Some internationally harmonized guidelines regarding specifications and tests, impurities and validation of analytical methods have particular relevance to the development of chiral drugs and are discussed below. In addition, the impact of work on the common technical document is considered. 

Figure 6.1 Diagrammatic representation of the organization of the Common Technical Document (CTD) (from ICH M4 Guide).

Readers may also be aware that under the auspices of the ICH a document is being developed on the organization of the Common Technical Document. It is intended that this will result in a common format (and, to at least some extent, content) of marketing authorization applications in the jurisdictions of those party to the ICH process (Japan, the EEA, and the United States). At the time of writing, a draft document had been circulated for comment. When adopted and implemented, this will result in a considerable amendment to the format and sequencing of information in a marketing authorization application. 

The Common Technical Document for the Registration of Pharmaceuticals for Human use 08-24-00... 

Figure 7.1 Common technical documentation. (Source ICH Harmonised Tripartite Guideline. Organisation of the Common Technical Document for the Registration of Pharmaceuticals for Human Use, M4, Step 4 Version (2004).)...

A Sponsor submits a clinical trial application to the Competent Authority in each member state where the trials are to be conducted. The Competent Authority has 60 days to review and approve or reject the application. Application is in prescribed forms and covers the proposed clinical trial protocol, manufacturing, and quality controls on the drug, and supporting data, such as (1) chemical, pharmaceutical, and biological data, (2) nonclinical pharmacological and toxicological data, and (3) clinical data and previous human experience. The supporting data are submitted in the Common Technical Document (CTD) format (see Section 7.11). 

International Conference on Harmonization. Organization of the common technical document for the registration of pharmaceuticals for human use, in Harmonized Tripartite Guideline, ICH, 2002. 

The common technical document (CTD) (ICH M4) is now a requirement. The CTD is the agreed common format for the preparation of a well-structured application to the regulatory authorities and has had an impact on all organisations as database integration and electronic submissions become more common. 

Directive 75/318/EEC required that the dossier be presented in four highly structured parts Parts I, II, III, and IV. Directive 83/570/EEC was the amending Directive, which introduced the requirements for a draft SPC to be produced by the applicant. Volume 2B of The Rules Governing Medicinal Products in the European Union gave a detailed breakdown of the structure of a European regulatory dossier. This format was accepted until the end of June 2003 when a new format known as the Common Technical Document (CTD) became mandatory (see later). 

Information on the Common Technical Document Presentation and format of the dossier CTD http //pharmacos.eudra.org/F2/eudralex/vol-2/ B/ctd2003july.pdf. 

ICHM4 Organisation including the granularity documents that provides guidance on document location and paginations (The common technical document) (Revised annex granularity document, November 20(B) Step 5... 

Prior to the Conference, during which the ICH Expert Working Group and Steering Committee met, the ultimate objective of ICH 5 was achieved. The Common Technical Document (CTD) was agreed (see Table 19.6 for finalised CTD), setting out a harmonised format (see below) for regulatory submissions. 

Zahn M. The Common Technical Document (CTD) Post-ICH 5. The Regulatory Affairs Journal-Pharma 2001 12 113-7. 

In June 2004 the Australian Regulatory Guidelines for Prescription Medicines (ARGPM) were issued by the TGA to replace the AGRDl. Under the ARGPM the format for registration applications in Australia is the Common Technical Document (CTD) developed through the International Conference on Harmonisation (ICH). 

As more than 95% of new medicines are worked out in the ICH regions the technical requirements for the safety, efficacy and quality of new medicines is determined at large by ICH technical guidelines. The application format for registration (marketing authorization) of new medicines in ICH and associated countries (such as Canada, Switzerland and Australia) has to follow The Common Technical Document (CTD) which provides harmonized structure and format for new product applications. This Common Technical Document is divided into four separate sections and 5 modules (see Fig. 1). The four sections address the application organization (M4 Organization), the Quality section (M4Q), the... 

The ICH Q8 guidance is currently being developed and is expected to reach the ICH Step 2 in November 2004. It is intended to provide guidance on the contents of Section State-of-the-the-Art Pharmaceutical Science. P.2 (Pharmaceutical Development) for drug products as defined in the scope of Module 3 of the Common Technical Document (ICH topic M4). 

Guidelines have been established to assist sponsors in the preparation of applications to register new prescription or other high-risk medicines for human use. The format for applications is the Common Technical Document. It is a format that is also used in other parts of the world. 

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