FDA, EMA officials encourage companies to pilot eCTD 4.0

BETHESDA, MD – Companies should increase their efforts to address issues and test their electronic Common Technical Document (eCTD) Version 4.0 before it becomes mandatory, according to regulators with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
In the EU, eCTD submissions in Version 4 will become mandatory for all centrally authorized products in 2027. The FDA will require mandatory eCTD submissions in Version 4 by 2029.

Regulators from FDA, EMA and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) discussed their initiatives to prepare the industry for implementing eCTD Version 4 on Tuesday at DIA’s Regulatory Submissions, Information and Document Management Forum. They also shared their experiences in testing these systems with companies and outlined the benefits of Version 4.

The International Council for Harmonisation (ICH) approved eCTD Version 4 as Step 4 in December 2015. However, the implementation of this new version will differ by region following the conclusion of the voluntary phase.

“We all know that eCTD 4 has been a bit of a skeptical topic of conversation over many years, but today in 2026, it’s really no longer a concept that we talk about. It’s becoming part of our reality,” said panel moderator Lorelle Leonienco of LORENZ Life Sciences Group.

The US, Europe, and Japan are now accepting voluntary applications in the eCTD Version 4 format while Japan will require mandatory submissions of this version sometime this year, she said.

Jonathan Resnick, project management officer at the FDA's Office of Business Informatics (OBI) in the Center for Drug Evaluation and Research (CDER), discussed some of the key benefits of eCTD Version 4.0 compared to version 3.2.2.

One of the main benefits is that Version 4 “eliminates the need to generate separate XML or backbone files” for Module 1 and study data in Modules 4 and 5, and a single format can be used for multiple agencies. The latest version eliminates the need to maintain separate regional models or XML files.

Another benefit is that migrating to 4.0 involves a “seamless technology transition for end users.” The changes from Version 3.2.2 to Version 4 are primarily “under the hood” meaning the five modules and the headings are still the same as in the previous version. “For the end user it doesn’t really change.”

Resnick noted that the FDA now can take an application that has already been submitted and switch it over to Version 4.

“FDA has the software to do this and we’re trying it and we are going through our implementation cycle.” The agency is currently working on this compatibility function and plans to have this ready by the fall 2026. “After this, there is nothing to stop you from submitting your applications in 4.0.”

Resnick said that ICH published a CTD v4.0 Implementation Guide on V1.6 May 2024 and that FDA has accepted eCTD Version 4 since fall 2024.

Resnick told the gathering that “we are accepting 4.0 submissions, we want to allow people to start testing this out and to send it in.” He said that when glitches come up during this submission, “We work with our vendor community and fix it and move forward.”

In preparation for when eCTD Version 4 becomes mandatory, Resnick advised companies to engage in discussions with their vendors about their development plans. Companies should also create a transition plan to move to eCTD Version 4. He also recommended that sponsors send any questions they have to the ICH or FDA and take the time to familiarize themselves with the concepts and enhancements of this version.

Kristiina Puusaari, senior coordinator of EMA’s digital business transformation program, said that the agency is currently piloting eCTD Version 4 for companies that manufacture centrally authorized products (CAPs). The learnings from the pilot will be published at the end of March 2026. In the second quarter of 2026, the EMA will pilot more complex scenarios of using this version for CAPs.

She also stressed the importance of end-to-end testing, and this process should replicate the actual production process as much as possible.

She also highlighted several challenges in implementing Version 4 of the eCTD in the EU. These challenges include differences among member states that hinder the establishment of a single repository and a unified submission portal. Additionally, there are varying legal requirements across different member states, as well as the use of diverse review tools. Furthermore, the integration levels of review tools and case management systems differ across member states.

Andrea Johnson, deputy director of future system business requirements for the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA), told the meeting that “we are not quite as far along as my colleagues, but we are making headway” in adopting Version 4.

Johnson said the agency is supporting Version 3.2 of the eCTD before moving to Version 4. The MHRA will eventually move to the later version of the eCTD but did not mention a date.

She acknowledged that one of the obstacles to implementing the eCTD Version 4 is migrating to a system that is separate from the EU system after Brexit.

Johnson told the meeting that “we are still in planning phase. When ready, we will undertake pilots with industry. Within two to three years, after consultation on a suitable date, we will make this mandatory.”

FDA, EMA officials encourage companies to pilot eCTD 4.0

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