Common Technical Document CTD

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

The main feature of the harmonisation is guidelines and Common Technical Documents (CTD). The CTD gives a harmonised format and content for new product applications and in 2003 there was an agreement on implementation, in USA, Europe and Japan. 

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). 

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. 

Subsequently, following agreement on Common Technical Document (CTD) format for the dossier. Commission Directive 2003/63/EC of 25 June 2003, replaced Aimex 1 of Directive 2001/83/EC (detailing scientific and technical requirements) with a new Annex (detailing scientific and technical requirements in CTD terms). Provisions are made in the legislation for the omission of data in certain circumstances where information is already available to the regulatory authorities from other sources, for example. 

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). 

It was generally assumed that following the ICH 4 meeting in 1997 that International Harmonisation had reached an interim conclusion and that the future would focus on developing a Common Technical Document (CTD), to improve efficiency in documenting new medicines for regulatory purposes. However, the ICH process... 

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. 

Common Technical Document (CTD). The meeting discussed the implementation of both the paper and electronic versions of the CTD with particular relevance to biotech products and new chemical entities. 

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

The application should be in the format of common technical document (CTD), which became mandatory from July 2003. The regional specific requirements are in the Modules 1 and 5 of CTD, which are described below. 

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... 

FIGURE 10 Schematic illustration of the ICH M4 common technical document (CTD) the contents of the Quality Overall Summary (2.3) and Quality (3) modules are most relative to PAT. 

The U.S. Food and Drug Administration (FDA) defines novel (new) pharmaceutical excipients as those substances used in the United States for the first time in a human drug product or by a new route of administration (1). The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) includes sections in its Common Technical Document (CTD) that details the information required for the approval of novel (new) excipients. Information on the control of excipients is included in Section P.4 of the CTD, and any additional information that may be required should be included in Appendix A.3 of the CTD. 

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. 

Idanpaan-Heikkila, J.E. ICH and the common technical document (CTD). WHO Drug Information 1999, 13, 78-81. 

If harmonization can be achieved, as it has been, across sufficiently broad areas of quality, safety and efficacy, there is no logical reason why a common technical document (CTD) or dossier cannot be prepared that would be acceptable to all dmg regulatory authorities. Movement to a CTD would appear to be the next step toward further internationalization. 

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