eCTD 4.0: What Regulatory Teams Need to Know About the Transition

What's Changing: eCTD 3.x vs. 4.0

XML Structure

eCTD 3.x: Uses a Document Type Definition (DTD) to define the XML backbone. The DTD specifies elements, attributes, and their relationships in a relatively rigid structure.

eCTD 4.0: Uses XML Schema Definition (XSD), which provides stronger typing, more flexible validation, and better support for complex data structures. XSD is the modern standard for XML schema definition and is consistent with how other healthcare data standards (like HL7 FHIR) describe their data models.

What this means for teams: Publishing tools need to generate XSD-compliant XML instead of DTD-compliant XML. Validation engines need to check against XSD-based rules. Any custom scripts, templates, or workflows that interact directly with the XML backbone will need to be updated.

Data Model

eCTD 3.x: The submission backbone is primarily a document-centric structure — it describes files, their locations in the CTD hierarchy, and their lifecycle operations (new, append, replace, delete).

eCTD 4.0: Incorporates structured FHIR resources alongside the document structure. Submissions reference FHIR resources for product information, substance data, organization details, and other structured data that was previously embedded in documents or maintained separately.

What this means for teams: Regulatory teams will need to manage structured data (product definitions, substance identifiers, organization records) in addition to documents. This data will need to conform to FHIR resource specifications and be maintained consistently across submissions.

IDMP Alignment

eCTD 3.x: Product identification relies on application-specific identifiers with no standardized data model for product information.

eCTD 4.0: Aligns with ISO IDMP (Identification of Medicinal Products) standards. Product and substance data will need to conform to IDMP data elements, including standardized identifiers for medicinal products, pharmaceutical products, substances, and organizations.

What this means for teams: Organizations need to assess their current product data against IDMP requirements and plan for data enrichment or restructuring. This is particularly impactful for organizations with large product portfolios or products registered in multiple regions.

Validation Rules

eCTD 3.x: Regional validation criteria are defined by each health authority (FDA, EMA, Health Canada, etc.) based on the DTD structure.

eCTD 4.0: New validation criteria will reflect the XSD structure, FHIR resource requirements, and IDMP data quality expectations. Validation will cover both the structural correctness of the submission and the quality/completeness of structured data.

What this means for teams: Publishing platforms need to update their validation engines to support eCTD 4.0 criteria as agencies publish them. Expect a period where validation rules are evolving and being refined as agencies gain experience with 4.0 submissions.

Transition Period

Health authorities have signaled that there will be a dual-format period during which both eCTD 3.x and 4.0 submissions will be accepted. The exact timeline varies by region:

• FDA: Has been actively involved in eCTD 4.0 development through ICH M8. Specific mandatory adoption dates have not been finalized as of early 2026.
• EMA: Has been aligning eCTD 4.0 planning with IDMP implementation timelines.
• Health Canada, TGA, PMDA: Expected to follow ICH guidance on adoption timelines.

The dual-format period means organizations need publishing tools that can produce both eCTD 3.x and 4.0 outputs during the transition.

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What This Means for Your Publishing Platform

Not all platforms are equally prepared for eCTD 4.0. The degree of readiness depends on how the platform's architecture was designed:

Platforms Built Around eCTD 3.x Assumptions

Many legacy publishing tools were designed with the eCTD 3.x DTD structure deeply embedded in their data models, assembly workflows, and validation engines. For these platforms, supporting eCTD 4.0 requires significant re-architecture — not just an update to templates or configuration files.

Signs that a platform may struggle with the transition:

• The publishing engine generates XML directly from hard-coded DTD templates
• Validation is tightly coupled to specific DTD elements and attributes
• There's no abstraction layer between the business logic and the schema-specific output
• The platform has no FHIR capabilities or structured data management

Platforms with Schema-Agnostic Architecture

Modern platforms that separate business logic from schema-specific output are better positioned. If the platform uses a modular architecture where the submission structure, lifecycle rules, and output format are configurable rather than hard-coded, the transition to XSD-based output is a configuration change rather than a rewrite.

Questions to Ask Your Vendor

1. "What is your eCTD 4.0 roadmap?" Look for specific milestones, not vague promises.
2. "Can you demonstrate dual-format support?" The platform should produce both 3.x and 4.0 from the same source content.
3. "How do you handle FHIR resources?" Does the platform have any FHIR capabilities today?
4. "How will validation work for 4.0?" Will the platform support 4.0 validation criteria as agencies publish them?
5. "Will migration require reimplementation?" Ask whether existing submissions and workflows will carry forward.

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What Regulatory Teams Should Do Now

Even though mandatory eCTD 4.0 adoption dates aren't finalized, there are concrete steps teams can take today:

1. Audit Your Current Platform's 4.0 Readiness

Talk to your publishing vendor. Ask the questions listed above. Understand where they are on the 4.0 roadmap and whether their architecture can support the transition without a complete reimplementation.

If your vendor can't articulate a clear 4.0 strategy, that's a signal to start evaluating alternatives now — before the transition deadline creates urgency.

2. Assess Your Product Data Against IDMP

eCTD 4.0's alignment with IDMP means your product data needs to conform to ISO standards for medicinal product identification. Start by:

• Inventorying your current product data elements
• Mapping them against IDMP data requirements
• Identifying gaps that need to be addressed
• Planning for data enrichment or restructuring

This is typically a multi-month effort for organizations with large portfolios, so starting early gives you runway.

3. Understand the FHIR Resource Model

Even a basic understanding of FHIR resources will help your team prepare. FHIR uses a modular, RESTful approach to healthcare data — each resource (Patient, Organization, MedicinalProductDefinition, etc.) is a self-contained unit with standardized structure and relationships.

For regulatory teams, the most relevant FHIR resources will be those related to product definition, substance identification, and organization records. Understanding how these resources work will make the 4.0 transition more intuitive when it arrives.

4. Plan for Dual-Format Support

During the transition period, your organization will need to publish both 3.x and 4.0 submissions. This means your publishing platform needs to support both formats simultaneously. Plan your workflows and quality checks for producing and validating submissions in both formats.

5. Stay Connected to Agency Guidance

Monitor ICH M8 working group updates, FDA guidance documents, and EMA communications about 4.0 adoption timelines. These will provide the specific dates and requirements your team needs to plan against.

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How DnXT Is Preparing for eCTD 4.0

DnXT Solutions is building for the eCTD 4.0 transition with several architectural advantages:

Schema-agnostic architecture: DnXT's modular design separates business logic from schema-specific output. The publishing engine uses a configurable approach where submission structure, lifecycle rules, and output format are abstracted from the underlying schema. This means the transition from DTD-based to XSD-based output is a configuration change at the platform level, not a fundamental rewrite.

FHIR-ready data model: DnXT is integrating HL7 FHIR resource support into the submission pipeline, enabling the structured data management that eCTD 4.0 requires.

Dual-format support: DnXT will support both eCTD 3.x and 4.0 output simultaneously during the transition period, allowing teams to publish in either format from the same source content.

Validation engine updates: DnXT's real-time validation engine will support eCTD 4.0 criteria as agencies publish them, ensuring submissions are validated against the latest specifications.

IDMP integration: Product and substance data management is being structured for ISO IDMP compliance, so organizations using DnXT will have a clearer path to the data quality requirements that 4.0 introduces.

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The Competitive Opportunity

Organizations that prepare early for eCTD 4.0 gain a competitive advantage. When the mandatory adoption dates arrive, prepared teams will transition smoothly while others scramble to upgrade legacy tools, restructure product data, and retrain staff.

For biotechs and mid-size pharma companies, this is particularly strategic: you can leapfrog larger competitors who are locked into lengthy vendor upgrade cycles. A modern, cloud-native platform that's building for 4.0 from the start gets you ahead of the curve without the multi-million-dollar platform migration project that large pharma will face.

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→ See DnXT's eCTD 4.0 readiness
→ Request a demo

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DnXT Solutions is a cloud-native regulatory platform building for the future of eCTD submissions. Learn more at dnxtsolutions.com.