eCTD Cross-Module Verifier

Overview

Verify consistency and data integrity of eCTD pharmaceutical dossiers. Cross-checks Module 2 (Summaries) against Module 5 (Clinical Study Reports) to ensure study references, p-values, N-counts, endpoints, and safety data are aligned before regulatory submission to FDA, EMA, or PMDA.

The skill targets the most common source of regulatory deficiency letters: inconsistencies between summary claims and source data. It addresses the ICH CTD structure (Modules 1–5) used globally by FDA, EMA, PMDA, Health Canada, and TGA.

• Cross-module integrity — Every study cited in Module 2 summaries must have a matching CSR in Module 5, and vice versa.
• Data synchronization — p-values, N-counts, and incidence rates in summary tables must exactly match the source CSR data.
• Regulatory compliance — Checks for ICH GCP (E6), ICH E3, ICH M4, and FDA 21 CFR Part 312 references.

Getting Started

Add your eCTD dossier content to the project workspace — either as a single structured markdown file with Module 2 and Module 5 sections, or as a directory with module-2/ and module-5/ subdirectories. Then activate the eCTD Cross-Module Verifier skill. The agent will guide you through cross-module verification, data sync validation, and report generation.

Example Conversation

Below is an example of how a typical cross-module verification session unfolds. The agent verifies dossier structure, checks data consistency, and helps resolve discrepancies.

You: I need to verify our eCTD dossier for compound RKN-4012 before we submit the NDA to FDA. The dossier files are in the workspace under ectd-rkn4012/.

Agent: I’ll run a cross-module integrity check on your dossier. Let me start by scanning the module-2/ and module-5/ subdirectories.

I found 3 files in module-2/ and 5 files in module-5/. Running the cross-module verifier now.

The verification found 2 errors and 3 warnings:

• ERROR: Study “RKN-4012-301” is referenced in Module 2.7.3 (Clinical Efficacy Summary) but has no corresponding CSR in Module 5.3.
• ERROR: “Deaths / mortality” is mentioned in Module 2.7.4 safety summary but not found in any Module 5 CSR.
• WARNING: Study “RKN-4012-PK-01” exists in Module 5 but is not referenced in Module 2 summaries.
• WARNING: ICH E3 CSR structure reference not found in dossier.
• WARNING: Endpoint “Overall Survival at 24 months” in Module 2 not matched in Module 5 endpoints.

The most critical issue is the missing CSR for study RKN-4012-301. Do you have that report available?

You: Yes, I forgot to add it. I’ve placed the CSR at module-5/rkn4012-301-csr.md. Can you re-run and also check the data sync between the efficacy summary and this CSR?

Agent: Re-running cross-module verification… The missing CSR error is resolved. Now running the data sync validator between your Module 2 efficacy summary and the new CSR.

The data sync found 1 mismatch:

• ERROR: p-value 0.0023 (summary line 47, primary endpoint ORR) → source CSR reports p=0.0021 (line 312).

This looks like a transcription rounding difference. The CSR uses 4 decimal places (0.0021) while the summary rounds to 0.0023. Should I update the summary to match the CSR value?

You: Yes, use the CSR value — it’s the source of truth.

Agent: Updated. Re-running validation — all clean now: 0 errors, 1 warning remaining (the PK study not yet summarized in Module 2). I’ve generated a verification checklist at output/ectd-verification-checklist.md for your records.

Sample Output Excerpt

Below is a representative excerpt from a cross-module verification report, showing the key sections reviewers care about most — study reference alignment and data consistency.

eCTD Cross-Module Verification Report — RKN-4012

Module 2 content: 45,230 chars | Module 5 content: 187,450 chars Studies in Module 2: 4 | Studies in Module 5: 5

Section Completeness

Cross-Module Consistency

Data Sync: Efficacy (Study RKN-4012-301)

Result: PASS — cross-module integrity appears sound.

Built-in Validation Tools

The skill includes two extension tools that automate the most labor-intensive parts of eCTD dossier QC.

What the tools check

Severity levels

• ERROR — A data mismatch or missing study/section that must be resolved before submission.
• WARNING — A potential gap or inconsistency that should be reviewed depending on context.
• INFO — Unfilled placeholders or source data not referenced in summaries (informational).

Example validation output

======================================================================
eCTD CROSS-MODULE VERIFICATION REPORT
======================================================================
Path: ectd-rkn4012/
Module 2 content: 45,230 chars
Module 5 content: 187,450 chars
Studies in Module 2: 4
Studies in Module 5: 5

--- SECTION COMPLETENESS ---
  All expected Module 2 and Module 5 sections found.

--- CROSS-MODULE CONSISTENCY ---
  [WARNING] Study "RKN-4012-PK-01" present in Module 5 but not
            referenced in Module 2 summaries.

--- REGULATORY REFERENCES ---
  Key regulatory references found.

--- UNFILLED PLACEHOLDERS ---
  Found 3 unfilled placeholder(s).
  [INFO] line 24: Unfilled placeholder: [SPONSOR NAME]
  [INFO] line 31: Unfilled placeholder: [SUBMISSION DATE]
  [INFO] line 89: Missing value: [VALUE]

--- SUMMARY ---
  Errors:   0
  Warnings: 1
  Info:     3

RESULT: REVIEW NEEDED — check warnings for potential gaps.
======================================================================

The agent runs both tools iteratively — first the cross-module verifier for structural integrity, then the data sync validator for each study pair — and surfaces findings inline so you can resolve issues before submission.