Common Technical Document (CTD): The Five Modules, Explained

The Common Technical Document is the agreed structure for a marketing application, developed through ICH as guideline M4.

Before the CTD, the same program had to be reassembled differently for FDA, the EU and Japan. The CTD harmonizes the format; the requirements still differ by region. The same study report sits in the same place whoever is reading it.

The five modules

Module 1 is not part of the CTD. It is region-specific by design, which is why the CTD is often drawn as a triangle with Module 1 sitting outside it. Modules 2 to 5 are common; Module 1 is what each authority adds on top.

Module 2: summaries

Reviewers typically read Module 2 first, and many application problems surface there.

• 2.1 Table of contents
• 2.2 Introduction
• 2.3 Quality Overall Summary
• 2.4 Nonclinical Overview
• 2.5 Clinical Overview
• 2.6 Nonclinical Written and Tabulated Summaries
• 2.7 Clinical Summary: 2.7.1 Biopharmaceutics, 2.7.2 Clinical Pharmacology, 2.7.3 Efficacy, 2.7.4 Safety

Module 2 summarizes what Modules 3 to 5 already contain, without new argument. Every number in it should be traceable to a source document. When a reviewer checks a figure in 2.7.4 against the study report and they disagree, the result is an information request at best.

Module 3: quality

Module 3 carries the CMC content, and it is the largest part of most applications:

• 3.2.S Drug substance: general information, manufacture, characterization, control, reference standards, container closure, stability
• 3.2.P Drug product: description, pharmaceutical development, manufacture, control of excipients, control of drug product, reference standards, container closure, stability
• 3.2.A Appendices: facilities and equipment, adventitious agents safety, excipients
• 3.2.R Regional information

For a biologic Module 3 weighs more still, because the license covers the manufacturing establishment as well as the product.

CTD and eCTD

The CTD is the structure. The eCTD is the electronic format used to submit it: an XML backbone describing the files, their placement in the module hierarchy, and their lifecycle across sequences.

Each sequence declares whether a document is new, replaces an earlier one, or is being deleted. The current dossier is the accumulated result of every sequence. Getting lifecycle operators wrong is how a supplement ends up referencing a superseded specification.

eCTD v4.0 is the successor format, based on HL7 RPS. FDA has accepted v4.0 submissions since September 2024, and EMA opened optional v4.0 use from December 2025. FDA's projected date for requiring it is 2029, so both formats will coexist for years. v4.0 is not urgent, but it belongs in the decision when choosing a publishing vendor.

Applications that use the CTD

CTD structure applies to marketing applications: NDAs, BLAs, ANDAs and their supplements in the US, and MAAs in the EU. INDs are not required to be in CTD format, though many sponsors build them that way anyway so the content carries straight through to the NDA rather than being reorganized later.