Japan eCTD v4.0 Submission Checklist: A Step-by-Step Guide

Phase 1 – Gap Assessment & Planning (3–6 Months Out)

1. Understanding eCTD v4.0: Attend workshops and webinars, from expert third party partners, on major changes from v3.2.2 to v4.0 like UUID concepts, lifecycle changes, sequence numbers, CV updates, single-package submissions and other key concepts of eCTD v4.0 – both regional and ICH mandated.
2. Review existing PMDA/ Global process: Conduct detailed gap analysis on existing submission processes and systems. Identify current process that doesn’t comply with new eCTD v4.0 requirements
3. Technology Assessment & CV Management
   • Schema & Validation Tools: Verify if your existing RIMS supports HL7 v3 RPS schemas and PMDA CVs
   • CV Synchronization: Ideally your regulatory publishing software (e.g., freya.fusion) should have a built-in CV manager to automatically pull in the latest PMDA and ICH controlled vocabulary updates in real time—so you never have to worry about manual imports or keeping CVs up to date.
   • Regulatory Intelligence: You should be able to identify any change in global or regional changes in guidance which can have impact on your submission - so you can finalize SOPs based on the latest standards.

4. Team Training & Change Management

   • Tool-Specific Sessions: Your team should attend your selected publishing software specific training sessions to understand the workflows, regional nuances and validation features
   • SOP Updates: Changes to existing SOPs to train the regulatory teams to adopt current process

   Not only Freya.fusion offers access to a curated repository of 100000+ verified regulations across 200+ markets, it also uses AI and agentic workflows to reduce the manual workload on your teams.

Phase 2 – Partner Identification, System Implementation & Testing (2–3 Months Out)

1. Expert Partner Collaboration: Identity and partner with an end-to-end regulatory service provider. Engage with partners who also provide local regulatory operations and services alongside global expertise

2. Software Integration

   • Identify the right software tool or sub-modules which are the right fit for your team needs.
   • Connect to existing DMS for seamless metadata and document sync

   For example, our Ai first tool, Freya.Fusion, is cloud-based unified RIMS. You can chose which module is right for you instead of paying license fees for the whole suite.

3. Schema & CV Validation Testing
   • Run sample exchanges against PMDA validation rules using you’re a regulatory software’s Sequence-Level Publishing capabilities.
   • Test CV scenarios—Prepare new and lifecycle sequences to check different controlled vocabularies scenarios like adding new category-event types, document types, code system values to confirm controlled vocabularies update without code changes in the software
4. User Acceptance & Pilot Submissions
   • Conduct at least one end-to-end pilot submission by preparing the initial-b and initial-c or initial-a types as reference submission and submit to the PMDA vial Electronic Gateway system to iron out transmission and validation quirks
   • Build eCTD v4.0 PMDA submissions (like reference or original) to set up strong concrete to align with requirements and enhance submission process without any hurdles
   • Review and validate your eCTD v4.0 submission using a eCTD v4.0 complaint validator and Viewer to thoroughly view the submission output.

Phase 3 – Content Preparation (1–2 Months Out)

1. Regional Administrative Information
   • Collect all PMDA-specific forms (cover letter, application form, labeling annex)
   • You should use a fully complaint tool to tag each form with its UUID and assign Context-of-Use keywords. Also apply the right templates to ensure every field (product name, applicant details, etc.) matches PMDA requirements
2. CTD Summaries (Quality, Non-Clinical & Clinical Overviews)
   • Break the Quality Overall Summary, Non-Clinical Overview, and Clinical Overview into XML-ready sections
   • Store each section as a reusable component with its UUID
   • Validate section headings and controlled-vocabulary values via selected your tool
3. Quality/CMC
   • Assemble CMC documents (drug substance/product reports, batch records, stability data)
   • Assign UUIDs and map metadata to PMDA CVs (e.g., “stability study,” “specification”)
   • Run CV checks to confirm all CMC metadata values are current
4. Non-Clinical Study Reports
   • Organize toxicology and pharmacology reports into required study-group order
   • Tag each study and its appendices with UUIDs
   • Execute PDF checks (hyperlinks, bookmarks) before XML conversion
5. Clinical Study Reports
   • Compile pivotal and supportive CSR documents, synopses, and integrated summaries
   • Pre-validate the assembled XML and metadata to catch any missing tags or mismatches

Phase 4 – Final Submission Preparation (Weeks Out)

1. Final Checks & Audit Trail
   • Confirm all UUIDs are correctly linked and no orphaned files remain. Generate audit logs and complete with 21 CFR Part 11-compliant e-signatures
2. Submission Transmission & Acknowledgement
   • Upload the single XML package to PMDA’s eCTD Gateway
   • Track acknowledgements and publication status in via a dashboard for live insights

Freyr’s latest platform, freya.Fusion, our Cloud based regulatory tool is industry’s first tool which is live for customer use with eCTD v4.0 module for Japan. It has all of the above mentioned functionalities and more.