Every US eCTD submission starts and ends with forms. The application form is literally the first thing an FDA reviewer expects to find, and a missing or misplaced form is one of the fastest ways to earn a refuse-to-file or a technical rejection. Yet forms are also one of the most misunderstood parts of eCTD structure — partly because of where they live in Module 1, and partly because the modern versions of these forms are dynamic XFA documents that behave nothing like ordinary PDFs.
This guide covers the forms you will actually use, where each one belongs in the eCTD structure, what happens to form leaves across submission lifecycles, and why so many teams discover — usually at the worst possible moment — that their PDF viewer cannot open the very forms they just submitted.
The FDA Forms You Will Actually Use
The forms that appear in day-to-day regulatory operations cluster around a handful of numbers:
| Form | Purpose | Used With |
|---|---|---|
| FDA 1571 | Investigational New Drug application cover form | INDs — every submission |
| FDA 1572 | Statement of Investigator | INDs — clinical site documentation |
| FDA 356h | Application to market a new drug or biologic | NDAs, BLAs, ANDAs and their supplements |
| FDA 2253 | Transmittal of advertisements and promotional labeling | Post-approval promotional submissions |
| FDA 3674 | Certification of compliance with ClinicalTrials.gov requirements | INDs, NDAs, BLAs — alongside the application form |
| FDA 3792 | User fee cover sheet | Fee-bearing applications |
The pattern worth internalizing: the application form (1571 or 356h) plus form 3674 travel together at the front of nearly every significant submission, while forms like 2253 define entire submission types of their own — a promotional-materials submission is essentially a 2253 plus attachments.
Where Forms Live in eCTD Module 1
US Module 1 is region-specific — its structure comes from the FDA’s us-regional specification rather than the ICH backbone that governs Modules 2 through 5. Forms belong in section 1.1 Forms, and the us-regional XML carries each form as its own leaf with a form-type attribute identifying which form it is. If you are new to how the regional backbone and the ICH backbone fit together, our guide to what eCTD actually is covers the architecture in detail, and the Module 1 deep-dive walks through the full US regional structure.
Three practical rules keep form placement clean:
- One leaf per form. Each form is an individual leaf in 1.1 with its own metadata — do not concatenate the 1571 and the 3674 into a single PDF.
- The form-type attribute matters. Validation engines and agency loaders read the machine-readable form type, not the filename. A correctly named file with the wrong form-type attribute is still wrong.
- Fillable means fillable. FDA expects the actual completed form, not a scan of a printout. Flattened scans lose the embedded data the agency’s systems extract automatically.
Why FDA Forms Break Standard PDF Viewers
Here is the part that surprises almost everyone. Open a recent FDA 1571 or 356h in most browser PDF viewers — including the open-source rendering engines embedded in many eCTD review tools — and you will not see the form. You will see a single page reading something like “Please wait… If this message is not eventually replaced by the proper contents of the document, your PDF viewer may not be able to display this type of document.”
That happens because modern FDA forms are XFA (XML Forms Architecture) documents, built originally in Adobe LiveCycle. An XFA form is not a fixed page of drawn text; it is an XML template plus a data layer that the viewer must execute to lay the form out. Dynamic XFA forms can grow and shrink — add a second investigator to a 1571 continuation section and the form inserts new rows at render time. The static “Please wait” page is just a fallback placeholder for viewers that cannot run the template.
The consequences for regulatory teams are real:
- Reviewers inside your own company cannot open the forms in the submission archive without desktop Adobe Acrobat.
- Web-based review portals silently show the placeholder page, and people assume the file is corrupt.
- QC steps that rely on visual inspection quietly skip the forms entirely.
This is why XFA support belongs on the checklist when you evaluate any eCTD viewer. DnXT Reviewer renders dynamic XFA forms natively in the browser — including dynamically generated rows — so a 1571, 356h, 2253 or 3674 opens as the actual form, exactly as an FDA reviewer sees it, without anyone installing desktop software.
Forms Across the Submission Lifecycle
Forms are also where eCTD lifecycle operations get subtle. Every sequence you submit — the original, each amendment, each annual report — typically carries a fresh application form leaf, because the form captures sequence-specific information such as the serial number and submission contents. That means the cumulative view of section 1.1 accumulates forms over time rather than replacing them, unlike, say, a protocol that gets replaced when amended.
Two failure modes to watch for:
- Wrong operation attribute. Submitting a new form with a replace operation against the previous sequence’s form rewrites history — the earlier sequence’s cumulative record loses its form. New sequence, new form, new operation.
- Cumulative-view gaps. If your publishing tool builds its cumulative and current views incorrectly, form leaves can disappear from the display even though the files are on disk and were accepted by the agency. When your reviewers say “the 356h is missing from sequence 0003,” verify against the raw sequence before assuming the submission itself was defective.
DnXT Publisher treats form leaves as first-class lifecycle citizens: the eCTD publishing engine assigns form-type metadata at placement time, carries forms correctly through new/replace/append operations, and the validation layer checks form presence per submission type before you publish — the same class of checks covered in our eCTD validation rules guide.
Practical Checklist Before You Submit
- Application form (1571 or 356h) present, completed, and not flattened
- Form 3674 included where clinical trials certification applies
- Each form is its own leaf in 1.1 with the correct form-type attribute
- Operation attribute is new for the sequence’s own forms
- Forms open correctly in an XFA-capable viewer — verify what the agency will actually see
- User fee form matches the fee status of the application
Frequently Asked Questions
Why does my FDA form show “Please wait…” instead of the form?
The form is a dynamic XFA document and your viewer cannot execute the XFA template. Open it in Adobe Acrobat or an XFA-capable review platform like DnXT Reviewer.
Does every eCTD sequence need a new application form?
Every submission to an application generally includes its cover form (1571 for INDs, 356h for marketing applications) reflecting that sequence’s contents and serial number.
Can I scan a signed paper form into the eCTD?
Wet-signature scans are generally discouraged; FDA expects completed electronic forms, and flattened scans lose the machine-readable data layer. Use electronic signatures on the electronic form.
See Your Forms the Way FDA Does
The fastest way to find form problems is to look at your submission through a viewer that renders exactly what the agency renders. Book a demo and we will load one of your own sequences — XFA forms included — into DnXT and walk through it together.
