Granularity is the decision about how much content goes into each file. It is made once, usually in a hurry before the first submission, and then lived with for the life of the application. Getting it right is one of the cheapest investments a regulatory team can make.
Key takeaways
- Granularity is how many documents a CTD section is split into.
- ICH sets the expected level for each module; some sections allow a choice.
- Finer granularity makes later replacements smaller and clearer.
- Decide it before authoring, and keep it consistent across sequences.
What granularity means
Every eCTD section can hold one document or several. Granularity is the choice of how content is divided into files: one document for the whole of a drug product section, or one per subsection; one clinical study report, or a report body with its appendices as separate files. The ICH granularity guidance sets out what is expected for each part of the CTD, and in several places it leaves the choice to the applicant.
It looks like a formatting decision. It is really a lifecycle decision, because in eCTD the unit of change is the document. Whatever is in one file is replaced together.
Why it matters later
Take a drug product section submitted as one large document. A year later a single specification changes. With coarse granularity the whole document must be replaced, the reviewer has to find what changed inside it, and the history shows a replacement of everything. With one document per section, the sequence replaces only the specification document, and the current view shows exactly what is new.
The same applies to clinical and nonclinical study reports. When a report body and its appendices are separate files, an amended appendix can be replaced on its own, and the reviewer can go straight to the part they need.
In eCTD the unit of change is the document. Whatever you put in one file, you will replace together.
Practical rules by module
- Module 2. Follow the ICH structure for summaries and overviews. Keep each summary as its own document so that an update to one does not drag the others along.
- Module 3. Place documents at the lowest heading level the guidance allows, especially in sections that change often after approval: specifications, analytical procedures, stability, and container closure.
- Module 4. Treat each study report as its own unit. Separate the report body from appendices where the content is large or likely to be amended.
- Module 5. Split clinical study reports along the ICH E3 structure where that helps: the report body, the protocol and amendments, and appendices such as listings as separate files. In the US, study tagging files describe what each file is — see our guide to study tagging files.
Common mistakes
- Changing granularity mid-application. Splitting a document that was filed whole means deleting or replacing the original and introducing several new files. Done carelessly, two versions end up in force.
- Going too fine. Splitting a document across files where the guidance expects one makes the dossier harder to read and can fail regional checks.
- Letting authors decide alone. Medical writers and CMC authors write to their own templates. Granularity needs to be agreed with whoever publishes, before the first draft.
Decide early and write it down. A one-page granularity plan for each module, agreed between authoring and publishing before the first sequence, saves rework in every sequence after it.
How DnXT approaches it
DnXT Publisher builds each region’s CTD structure from its own specification, so documents are placed at the section level that region expects, and lifecycle is chosen per document against the current view. Our publishing desk agrees a granularity plan with each sponsor before the first sequence.
Plan granularity before the first sequence
Talk to our publishing team about structuring a new application so it stays easy to maintain.
