# eCTD Cross-Module Verifier

> 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.



Tags: Healthcare, Pharmaceutical, Regulatory, Compliance, ICH GCP, FDA


## Example Prompts

- Verify that all studies in Module 2 summaries have matching CSRs in Module 5
- Check if p-values and sample sizes in my eCTD summary tables match the source CSR data
- Run a cross-module integrity check on my eCTD dossier before FDA submission

URL: https://rakenne.app/skills/ectd-cross-module-verifier/index.md

Try this skill: https://rakenne.app/a/?skill=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

| Module 2 Section | Status |
|-----------------|--------|
| 2.4 — Nonclinical Overview | OK |
| 2.5 — Clinical Overview | OK |
| 2.7.3 — Summary of Clinical Efficacy | OK |
| 2.7.4 — Summary of Clinical Safety | OK |
| 2.7.6 — Individual Study Summaries | OK |

| Module 5 Section | Status |
|-----------------|--------|
| 5.2 — Tabular Listing | OK |
| 5.3 — Clinical Study Reports | OK |
| 5.3.5 — Efficacy and Safety Reports | OK |

#### Cross-Module Consistency

| Check | Result |
|-------|--------|
| Study RKN-4012-201 (Module 2 → Module 5) | MATCH |
| Study RKN-4012-301 (Module 2 → Module 5) | MATCH |
| Study RKN-4012-302 (Module 2 → Module 5) | MATCH |
| Study RKN-4012-PK-01 (Module 5 only) | WARNING — not summarized in Module 2 |
| AE data: Module 2.7.4 ↔ Module 5 CSRs | MATCH |
| SAE counts: Module 2.7.4 ↔ Module 5 CSRs | MATCH |
| Deaths: Module 2.7.4 ↔ Module 5 CSRs | MATCH |

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

| Data Point | Summary | Source CSR | Status |
|-----------|---------|-----------|--------|
| ITT N (treatment) | N=287 | N=287 | MATCH |
| ITT N (placebo) | N=291 | N=291 | MATCH |
| ORR p-value | p=0.0021 | p=0.0021 | MATCH |
| PFS HR (95% CI) | 0.62 (0.49–0.78) | 0.62 (0.49–0.78) | MATCH |
| OS median (treatment) | 18.4 months | 18.4 months | MATCH |

**Result: PASS** — cross-module integrity appears sound.

<!-- /excerpt -->

## 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

| Check Category | `cross_module_verifier` | `data_sync_validator` |
|---------------|:-----------------------:|:---------------------:|
| **Module 2 section completeness** | All sections 2.2–2.7.6 | — |
| **Module 5 section completeness** | All sections 5.2–5.3.5 | — |
| **Study reference alignment** | Module 2 ↔ Module 5 cross-refs | — |
| **Endpoint consistency** | Primary/secondary endpoint matching | — |
| **Safety data cross-references** | AEs, SAEs, deaths, discontinuations | — |
| **Regulatory citations** | ICH GCP, E3, M4, 21 CFR 312 | — |
| **p-value matching** | — | Summary vs. source CSR p-values |
| **N-count matching** | — | Summary vs. source sample sizes |
| **Percentage cross-check** | — | Detects transcription issues |
| **Unfilled placeholders** | Flags remaining markers | — |

### 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.


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