# ICH E6 Investigator Brochure (IB) Author

> Author and maintain ICH E6(R3)-compliant Investigator Brochures for investigational medicinal products, including Reference Safety Information, annual update/change-control summaries, and investigator-facing risk digests aligned with FDA IND, EU CTR, CIOMS V, and ICH E2A expectations.



Tags: ICH, E6(R3), Investigator Brochure, Clinical Trials, GCP, Pharmacovigilance, Regulatory Writing, FDA, EU CTR, RSI, SUSAR


## Example Prompts

- Draft a full ICH E6(R3) Investigator Brochure for our first-in-human oncology IMP, including RSI
- Prepare the annual IB update letter and change-control summary for our IND annual report
- Revise the Reference Safety Information after new SAE line-listing data and flag SUSAR expectedness impacts
- Create a one-page physician and CRA pocket guide from the approved IB

URL: https://rakenne.app/skills/ich-e6-investigator-brochure/index.md

Try this skill: https://rakenne.app/a/?skill=ich-e6-investigator-brochure


## Overview

Author and maintain ICH E6(R3)-compliant Investigator Brochures for investigational medicinal products, including Reference Safety Information, annual update/change-control summaries, and investigator-facing risk digests aligned with FDA IND, EU CTR, CIOMS V, and ICH E2A expectations.

## What It Covers

- Full Investigator Brochure drafts with the seven ICH E6 sections in order.
- Distinct Reference Safety Information (RSI) tables for SUSAR expectedness workflows.
- Annual update letters and change-control summaries for FDA IND and EU CTR contexts.
- Investigator-facing Q&A summaries and physician/CRA pocket guides tied to a controlled IB version.

## Example Conversation

> **You:** We are preparing our first IND for ABC-101 and need an Investigator Brochure template with RSI. We have nonclinical tox summaries but no human data yet.
>
> **Agent:** I’ll create a full ICH E6(R3) IB structure, preserve missing clinical data as `[PENDING]` placeholders, and add a controlled RSI section that only lists expected serious adverse reactions supported by your source data. I’ll also cite 21 CFR 312.55 and EU CTR Annex I Section J where they affect distribution and submission.
>
> **You:** We also need the annual update package once Phase 2 exposure is available.
>
> **Agent:** I’ll prepare a change-control summary mapped to ICH E6 §7 sections, include an RSI change table, and flag how the new safety information maps to 21 CFR 312.33 IND annual report categories and EU CTR/CTIS impact assessment.
> 

## Sample Output Excerpt

The excerpt below shows the style of a controlled RSI and annual update section generated by the skill.

---

### Reference Safety Information (RSI)

**Controlling document:** Investigator Brochure v4.0, effective 2026-04-30<br>
**Data lock point:** 2026-03-31<br>
**Use:** Expectedness assessment for SUSAR reporting under ICH E2A / CIOMS V and EU CTR practice.

| MedDRA SOC              | Preferred Term            | Expected serious adverse reaction                          | Evidence basis                                                                  | RSI change              |
| ----------------------- | ------------------------- | ---------------------------------------------------------- | ------------------------------------------------------------------------------- | ----------------------- |
| Immune system disorders | Anaphylactic reaction     | Expected SAR for IV administration                         | Study ABC-101-201 SAE narrative 014 and cumulative safety table, DLP 2026-03-31 | Added in v4.0           |
| Hepatobiliary disorders | Drug-induced liver injury | Expected SAR when ALT/AST >5× ULN with bilirubin elevation | Integrated Phase 1/2 safety analysis, hepatic signal evaluation memo            | Wording revised in v4.0 |

### Annual Update Change-Control Summary

- **ICH E6 §7 Section 4:** Updated repeat-dose toxicology exposure margin discussion.
- **ICH E6 §7 Section 5:** Added Phase 2 exposure and serious adverse reaction summary through the data lock point.
- **ICH E6 §7 Section 6 / RSI:** Added one expected SAR and revised one PT wording based on cumulative safety review.
- **Regulatory map:** Changes support the FDA IND annual report safety update under 21 CFR 312.33 and require investigator distribution under 21 CFR 312.55.

<!-- /excerpt -->

## Extension Tools

**`validate_investigator_brochure`** validates a Markdown or text IB, RSI-only revision, or annual update package. It checks for:

- ICH E6 section presence and order for full IBs.
- Distinct RSI label, MedDRA SOC/PT fields, expected serious adverse reaction language, source traceability, version control, and SUSAR expectedness basis.
- Annual update elements such as prior edition comparison, change log, 21 CFR 312.33 mapping, EU CTR/CTIS impact, and investigator distribution plan.
- Inline references to ICH E6(R3) §7, 21 CFR 312.55, and EU CTR Annex I Section J.

## Getting Started

Upload or paste the current IB, CMC/nonclinical summaries, clinical safety data, RSI table, SAE line listings, and any prior edition change logs. Tell the agent whether you need a full initial IB, an annual update package, an RSI-only revision, or a site-facing digest. The skill will draft the requested deliverable, mark missing evidence with clear placeholders, and run validation before finalizing.



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