United States

FDA's CDER and CBER have accepted new regulatory applications in eCTD v4.0 format since 16 September 2024. Unlike v3.2.2, v4.0 removes the distinction between the ICH part and the regional part: modules 1–5 share a single backbone, with support for document reuse and fuller lifecycle management. Under the ICH regional implementation table, the US is planned to become mandatory in 2029. FDA has not announced a final cutover date; forward compatibility for applications originally established in v3.2.2 has been supported since 16 October 2026, and two-way communication is planned for later phases.

v4.0 remains voluntary. A clear transition window is widely expected ahead of the mandatory switch; plan your publishing toolchain, XML backbone and metadata practices early rather than waiting for the deadline to approach. Version note: the ICH endorsed IG v1.7 and CV v1.0.3 in June 2026, while FDA's table still lists IG v1.6 / CV v1.0 for the ICH packages — an ICH release does not mean FDA adoption; FDA's own regional files iterate separately, with the Regional M1 IG at v1.9 and the Regional CV package at v1.2 supported from 2026-09-28. Configure toolchains against the versions listed on FDA's page. Separately, FDA has announced that from 16 January 2027 it will technically reject v4.0 submissions failing the new high-severity criteria eCTD4-084, eCTD4-085 and US-eCTD4-561 through US-eCTD4-564.

The eCTD version FDA currently mandates, built on the eCTD specification v3.2.2 issued by the ICH M2 Expert Working Group. Since 5 May 2017, NDAs, ANDAs and BLAs must be submitted in eCTD format; from 5 May 2018 the requirement extends to commercial INDs and DMFs. Structurally, v3.2.2 splits the CTD into an ICH part (modules 2–5, harmonised globally) and a regional part (module 1, defined by each regulator).

This is the working format for the vast majority of live applications. The regional Module 1 specification, validation criteria and forms are collected on the FDA eCTD page; the submission channel is ESG NextGen. Provenance of 'Regional Module 1 v3.3': the version comes from the title of FDA's submission standards page, 'Submission Standards for eCTD v3.2.2 and Module 1 v3.3'. FDA publishes no standalone M1 v3.3 specification document; the Module 1 content is carried by the two Addenda to the eCTD Backbone Files Specification for Module 1 (both v2.3), Example Submissions v1.4, and the Comprehensive Table of Contents Headings and Hierarchy v2.3.5. Also note: FDA has announced it will technically reject, from 16 January 2027, submissions that fail the new high-severity validation criteria (2024 and 2025) — publishing toolchains must pass the new criteria before that date.