Common Technical Document

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The Common Technical Document ( CTD ) is a prescribed document format in which a pharmaceutical company must document the pharmaceutical quality, safety and effectiveness of a drug within the scope of drug approval and submit it to the drug authorities .

History and meaning

The Common Technical Document was developed as part of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) to harmonize drug approval conditions in the European Union , the USA and Japan . A first version of the specification was adopted in 2000; the third revision from January 2004 is currently valid. The Common Technical Document is now mandatory for most submissions in all three regions; it has also been adopted by Canada and Switzerland . The harmonization makes it possible to submit largely identical approval documents for a new drug in different countries.

structure

Modular structure of an approval application

The structure of a CTD consists of five modules:

  • Module 1: Administrative Information
  • Module 2: Table of contents, overview and summaries of modules 3–5
  • Module 3: Pharmaceutical Quality (Proof of Quality)
  • Module 4: Preclinical study reports (proof of effectiveness and harmlessness)
  • Module 5: Clinical study reports (proof of effectiveness and harmlessness)

Module 1

In contrast to the other modules, module 1 contains different documents from region to region. Therefore module 1 is not considered part of the CTD. In Europe, the following elements can be found in Module 1:

  • 1.1 Comprehensive table of contents for the entire dossier
  • 1.2 Application form for admission
  • 1.3 Product information: Summary of Product Characteristics (SmPC), package insert , information on packaging
  • 1.4 Information about experts involved
  • 1.5 Specific requirements for different types of applications
  • 1.6 Assessment of environmental risks
  • 1.7 Information on market exclusivity for orphan drugs
  • 1.8 Information on the pharmacovigilance system
  • 1.9 Information on clinical studies conducted outside the EU

Module 2

Module 2 provides an overview of the information on the drug in the dossier and integrates it with assessments and conclusions.

  • 2.1 Table of contents of modules 2 to 5
  • 2.2 Introduction (one page): Brief description of the pharmaceutical class, the mechanism of action and the intended clinical application.
  • 2.3 Summary on pharmaceutical quality (no more than 40 pages; for biotechnological pharmaceuticals : 80 pages): Overview and summary of the data from Module 3.
  • 2.4 Non-clinical overview (no more than 30 pages): integrated analysis of the non-clinical information in the dossier (overviews of the non-clinical test strategy, pharmacology , pharmacokinetics and toxicology as well as an integrating overview and conclusions). It must be stated to what extent the studies were carried out in accordance with Good Laboratory Practice .
  • 2.5 Clinical overview (approx. 30 pages): integrated analysis of the clinical information in the dossier (justification for product development, overviews on biopharmacy , clinical pharmacology , effectiveness, safety and conclusions on benefits and risks). It must be stated to what extent the studies were carried out in accordance with Good Clinical Practice .
  • 2.6 Non-clinical summaries and table overviews of all non-clinical studies on pharmacology, pharmacokinetics and toxicology carried out and presented in module 4 (no more than 100–150 pages).
  • 2.7 Clinical summaries of biopharmaceutical studies, clinical pharmacological studies, clinical studies on efficacy, summaries of clinical safety, literature references and synopses of the individual clinical studies presented in module 5 (usually 50–400 pages).

Module 3

Module 3 presents in detail the chemical-pharmaceutical and biological data on the medicinal substance and the product in the form of a medicinal product. Alternatively, a certificate of conformity (CEP) from the EDQM can be submitted for the ingredients ; A detailed description of the production and quality control in module 3 is then not required for these substances. For data on drugs, reference can also be made to a Drug Master File if the drug manufacturer and the drug manufacturer are not identical.

  • 3.1 Table of contents for module 3
  • 3.2.S data on the substance, the structure, the substance properties, the manufacturer, the manufacturing process, the in- process control , the starting materials, the intermediate products, the process validation and the development of the manufacturing process, as well as information on substance characterization, impurities, specifications, analysis methods and their validation , reference substances and finally data on the stability of the substance under various environmental conditions.
  • 3.2.P data on the product; Description and exact composition of the drug for all dosage forms and dosages, including information on all auxiliary materials and, in turn, data on manufacture, process validation, analysis, primary packaging and stability of the finished product.
  • 3.2.A Appendices which, if applicable, contain the description of special process plants or equipment, the safety assessment of additives or the description of novel auxiliary materials.
  • 3.2.R Regional information, which is documents specific to the relevant region (European Union, USA or Japan) on the quality of the medicinal product or active ingredient.
  • 3.3 Bibliography

Module 4

Module 4 presents in detail all study reports on all non-clinical (= not performed in humans) studies.

Module 5

Module 5 presents in detail all study reports on all clinical (= human) studies.

  • 5.1 Table of contents for module 5
  • 5.2 Tabular overview of all clinical studies
  • 5.3 Study reports on biopharmacy, pharmacokinetics, pharmacodynamics, efficacy and safety, as well as information on experiences with the product already marketed (if available) and all case report forms and a list of all participating patients.
  • 5.4 Bibliography

Electronic filing

The Common Technical Document defines a paper format; a complete dossier often comprises tens of thousands of pages. In order to make these data volumes easier to handle for applicants and authorities, an electronic format, the eCTD , was defined within the framework of the ICH, the content of which is based on the CTD.

Other uses of the CTD format

In addition to the application for approval of a new drug, the CTD format is now also used to maintain the approval documents. Pharmaceutical companies must submit changes to approval data, so-called change notifications, in CTD format.

The Drug Master File , which is used when the manufacturer of the drug and the manufacturer of the drug are not identical, also uses the format of the CTD Part 3.2.S.

Finally, parts of the CTD format are used for approval applications for clinical studies. In these applications, a dossier on the investigational medicinal product , in Europe a so-called Investigational Medicinal Product Dossier (IMPD), must be submitted, the structure of which follows module 3 of the CTD.

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