Regulatory glossary

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

The Common Technical Document is the agreed structure for a marketing application. It was developed through ICH as guideline M4, and it settled a question that used to cost sponsors months: what shape should a dossier be in.

Before the CTD, the same programme had to be reassembled differently for FDA, the EU and Japan. The CTD does not harmonise the requirements — those still differ by region — but it harmonises the container, so the same study report sits in the same place whoever is reading it.

The five modules

The distinction in that last column is the one people miss.

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: the summaries reviewers read first

Module 2 is where a reviewer forms their first impression, and it is disproportionately where applications go wrong.

• 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 is not a place for new argument. It summarises what Modules 3 to 5 already contain, and 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, characterisation, 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 this is the heart of the review, because the licence 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.

That lifecycle is the part worth understanding. An eCTD submission is not a snapshot; 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. Do not treat v4.0 as urgent, and do not treat it as far enough away to ignore when choosing a publishing vendor.

Which applications use it

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 reorganised later.