Prepare for eCTD v4: Lessons from the EMA Technical Pilot

September 2025 marked a milestone as the European Medicines Agency’s (EMA) eCTD v4 technical pilot came to an end. As the proud provider of choice for the EMA's eCTD v4 submission process and validation solution, we take the opportunity to review the course of events so far and summarize them for you. That is why in this blog post, we navigate you through...

• The EMA Pilot objectives,
• The different Pilot Phases,
• Participating stakeholders,
• Technical findings
• Practical implications for both regulators and life sciences companies. It highlights key milestones, validation updates and readiness actions that regulatory information management (RIM) teams should prioritize as eCTD v4 adoption advances.

Background: why eCTD v4 matters

eCTD v4 (the Electronic Common Technical Document, version 4.0) is the next step in electronic submissions worldwide. It makes managing document lifecycles easier, organizes metadata more clearly, and improves how content management systems interact with regulatory review tools. To ensure a smooth transition, major authorities and software vendors worldwide have been taking part in pilot programs and technical readiness tests.

What the EMA eCTD v4 pilot set out to do

The European Medicines Agency (EMA) set up a phased technical pilot starting at the end of 2024 to make sure submission tools work well together, are compatible with the agency’s review systems, and can handle real-world submission scenarios - ranging from simple test packages to more complex lifecycle cases. By running the pilot in stages, the EMA can identify and resolve technical issues before making any official requirements.    

The four phases of EMA’s eCTD v4 pilot
The EMA’s eCTD v4 pilot was designed to test every step of the submission process in a structured, practical way. By breaking the pilot into phases, both authorities and applicants could identify issues early and ensure a smooth transition to the new standard:    .

Phase 1 – Testing EMA eCTD v4 Submission Management Process and mock packages

The journey began with vendors submitting test packages and metadata to confirm they followed the eCTD v4 schema and used the correct controlled vocabularies. Applicants then put the system to the test with four realistic scenarios: converting an existing eCTD v3 submission to v4, submitting a duplicate application, creating a validation response (Submission Unit 2), and handling post-authorization documents (Submission Unit 3). This phase ensured that the tools and metadata were ready for real-world submissions.

Phase 2 – Mock submissions and system checks

Next, applicants and vendors ran mock submissions to see how packages would perform in the EMA’s review systems. Almost all submissions could have been viewed by the EMA using EXTEDO’s viewing solution, EURSnext. As eCTD v4 submissions are no longer readable by humans, using a viewer is necessary to ensure continued regulatory compliance.
To smooth out initial issues with some submissions not passing the required validation criteria, EMA and EXTEDO worked together on an enhancement of the EMA internal validation. This enhanced validator allows to display errors even better and provides more detailed feedback to the piloting companies. This phase was extended until the end of September 2025, giving participants extra time to test, provide feedback, and help refine the review tools.

Phase 3 – Preparing for lifecycle continuity and grouped submissions

The final focus of the pilot is on managing lifecycles and grouped submissions, ensuring that dossiers transition smoothly from eCTD 3.2 to v4. Attention is also given to forward compatibility of metadata. If all goes as planned, initial Go-Live will begin by the end of 2025 with centrally authorized products (CAPs), marking the first official use of eCTD v4 in practice.

Who participated in EMA’s eCTD v4 pilot

• EMA - leading the EU technical pilot, coordinating with national authorities and looking at alignment with other major health authorities
• Regulatory software vendors like EXTEDO whose customers submit using the respective solution.
• Industry sponsors and applicants who supplied submissions and tested real-world scenarios. EXTEDO had the opportunity to accompany several customers from all over the world, e. g. Veristat, Asphalion or Groupe ProductLife, while they were preparing their submissions. We are happy that all of them submitted successfully to EMA during the pilot.
  
  

Key technical findings & updates

• Validation criteria and controlled vocabularies:
  EMA has published draft validation criteria and updated controlled vocabularies for eCTD v4, which are a central input for authoring tools and RIM systems. These criteria incorporate legacy rules where applicable and include new schema checks specific to v4.

• Interoperability gaps: Pilot submissions revealed issues with metadata mapping, such as context groups, keyword lifecycles, and priority numbers, as well as problems with the interaction between content management systems and compilation components. These issues can be resolved through updates to tooling and internal processes.
  
  
• Rendering and agency ingestion improvements: Continued pilot submissions and repeated fixes to the EMA review tool resolved rendering issues and clarified the handling of Module 1 and other region-specific elements.

Practical implications for regulators and industry

• For regulators: The pilot helps authorities fine-tune validation rules and submission checks. Ongoing dialogue with industry and other stakeholders is important to ensure everyone is aligned on how document lifecycles and grouped submissions should be handled.

• For industry sponsors: Now is the time to check that internal processes, systems, and metadata are ready for eCTD v4. Engaging with vendors and authorities will help ensure a smooth transition. Find a quick check list here:

• Validate systems: Ensure CMS, RIM, and validation tools are eCTD v4-ready.
• Align metadata: Map internal fields to EMA's controlled vocabularies and validation criteria.
• Run mock submissions: Test packages with vendor tools and EMA environments.
• Plan migration: Define steps to transition lifecycles from eCTD 3.2 to v4.
• Train teams: Build understanding of new tagging and lifecycle concepts.
• Engage partners: Work with vendors and authorities to share feedback and stay aligned.
  
  

If you would like to learn in detail about the next steps towards eCTD v4 and how you can support a smooth transition in your organization, please read our blog post Navigating the Transition Between eCTD v3.2 and eCTD v4 | EXTEDO.

EMA eCTD v4 Pilot: Live Testing, Evolving Rules, and Time to Prepare

The EMA’s eCTD v4 pilot has transitioned to the technical interoperability and mock submission phases, and the timeline has been extended to allow for additional testing and refinement. The exact timing is still uncertain as the validation rules and processes are being adjusted. Therefore, it is important to closely monitor the EMA eSubmission pages and updates to the validation criteria to stay informed about milestones and deadlines.

The pilot is functioning as intended. It is iteratively identifying gaps, strengthening validation rules, and encouraging both tools and sponsors to prepare. This iterative process means that change is coming - not overnight, but steadily - and organizations that act early will have the advantage.

Regulatory teams need to prepare now. Review your processes, update your submission tools, and build internal readiness for evolving validations. With our comprehensive offering, EXTEDO is ready to support you through migration and the implementation of compliant tools to enable a smooth and safe transition for your regulatory business processes.