Your First IND in eCTD: A Sequence 0000 Checklist

For a small biotech the first IND is often the first eCTD submission the company has ever made. The science has had years of attention. The submission mechanics get a few weeks — and that is where avoidable delays come from.

Why sequence 0000 deserves a plan

Since 2018, FDA has required commercial INDs to be submitted electronically in eCTD format. The first submission is sequence 0000, and everything that follows — protocol amendments, information amendments, safety reports, annual reports — is built on top of it. Decisions made now about structure, naming and granularity will be inherited by every later sequence. A little planning makes the next hundred submissions easier.

1. Get the application number early

An eCTD envelope needs the application number. For a new IND, request a pre-assigned application number from FDA ahead of time, and record it once in the place your submission is built from. Typing it by hand into several places is how envelope errors start — and envelope errors are among the most common high-severity validation findings.

2. Set up the gateway and test it

Submissions reach FDA through its Electronic Submissions Gateway. Setting up an account, obtaining a digital certificate and sending a test submission takes time, and it involves people outside the regulatory team. Start weeks before you plan to submit, not days. If a publishing partner will transmit for you, confirm whose account will be used and how acknowledgements will reach you.

3. Know what goes in Module 1

Module 1 is the US regional module. For an initial IND it typically holds the Form FDA 1571, the certification of compliance with ClinicalTrials.gov requirements (Form FDA 3674), the cover letter and the investigator’s brochure, along with other administrative documents your IND needs. The rest of the IND content — the protocol, chemistry, manufacturing and controls information, pharmacology and toxicology data and previous human experience — goes in Modules 2 to 5 under the CTD headings. Our page on eCTD Module 1 explains the regional structure.

4. Agree the plan before documents are final

List every document, the CTD section it belongs in, and its owner. Agree granularity — how each section is split into files — with whoever will publish, before authors finish writing. Settle file naming and PDF settings at the same time: embedded fonts, searchable text, bookmarks to the expected depth, and hyperlinks that point to the right page. Fixing these during publishing week is where time goes.

Decisions made in sequence 0000 are inherited by every sequence after it.

5. Build, validate, fix, re-run

Assemble the sequence and validate it against FDA’s current eCTD criteria at FDA’s own severity. Any high-severity finding means a technical rejection: the submission is not filed and nothing starts until a corrected sequence arrives. Fix the cause at the source, rebuild, and run again until the report is clean. Keep the final report with the sequence you transmit.

6. After you send it

Watch for the gateway acknowledgements, which confirm receipt and, later, whether the sequence passed FDA’s checks. Under FDA’s regulations a clinical investigation may begin 30 days after FDA receives the IND, unless FDA tells you otherwise. Keep a record of what was sent and when — the next sequence will need to reference it.

How DnXT can help

Our publishing desk prepares and publishes first INDs for sponsors that would rather not build a publishing team: you review the plan for your sequence through a secure link, confirm or flag each document, and receive the validated sequence and its report. The same work runs on DnXT Publisher if you prefer to do it yourself. See how one IND sequence was assembled from a client-reviewed plan.