---
title: "Investigator's Brochure Authoring, Linked to the Protocol | Trelice"
description: "One Investigator's Brochure per product in Trelice: protocols prefilled from it, editions with a generated summary of changes, and a structured RSI table."
canonical_url: "https://www.trelice.com/investigator-brochure"
---

Investigator's Brochure

# One brochure per product, every protocol in step

The Investigator's Brochure is the document every protocol for a product depends on, and in most organizations it is a 100 to 300 page Word file rebuilt once a year by five departments. Trelice keeps one brochure per investigational product, links it to every protocol that uses the product, and carries each year's update as an edition whose summary of changes is generated.

[Book a demo](/contact) [Read the docs](/docs)

## What an Investigator's Brochure is

The Investigator's Brochure (IB) is the sponsor's compilation of the nonclinical and clinical data on an investigational product that is relevant to its study in humans. Investigators and ethics committees read it to judge whether the dose, the monitoring and the risks in a protocol are justified by what is known about the product. ICH E6(R3) Appendix A sets its contents, from a title page carrying the product's codes and names, the edition number, the release date and the edition it supersedes, through the nonclinical and clinical data, to a closing summary of data with guidance for the investigator.

The same document serves other regimes. In the United States, 21 CFR 312.23(a)(5) lists the five elements an IND must carry about the drug, from substance and formulation to the risks and precautions to expect, and 312.55 requires the sponsor to keep investigators informed through periodically revised brochures. In the European Union, Regulation 536/2014 Annex I asks for a brochure per ICH E6 with a clearly identified Reference Safety Information section. All of them expect the brochure to be reviewed at least once a year and revised whenever significant new information appears.

In practice it is a 100 to 300 page Word file. Nonclinical, CMC, clinical pharmacology, drug safety and medical writing each own a part, the annual revision is assembled by hand from study reports and the previous edition, the summary of changes is written from memory, and the protocols that quote it are checked against it by whoever remembers to. Trelice treats the brochure as a structured, reviewed document, the way it treats the protocol.

## One brochure per product, shared by every study

A brochure describes a product, not a study, so Trelice keeps it at the level of your organization rather than inside any one protocol. The anchor is an investigational product registry: each compound, biologic or device you study is an entry, with its sponsor code, names and kind, and each carries its own brochure line. An organization running five compounds has five brochures, each with its own edition history, pending updates and annual review date.

Studies link to the products they use, with a role: investigational product, comparator, background therapy. The brochure follows the product across those links, so each protocol knows which brochure, and which edition of it, describes the product it studies.

Editions are the unit of versioning. Each carries its edition number, release date and data cut-off date, and names the edition it supersedes, as the ICH title page asks. A released edition is immutable; the next one starts as a draft copied from it. Addenda between editions, for significant safety information that cannot wait a year, go through the same machinery as a short document of their own.

## The first study: brochure from the protocol, or protocol from the brochure

The first protocol for a new product can start from either side. If the brochure already exists in Trelice, the protocol is prefilled from it, as the next section describes. If the protocol is written first, the brochure can be created from it: product identity, formulation, mechanism of action, background summaries, dose rationale and adverse events of special interest are copied across deterministically, once, into the brochure’s structured fields, which are the source of truth for those facts from then on. Either way nothing is retyped and no AI invents anything.

Creating a protocol includes a guided step for the brochure. It asks which investigational product the study uses, or lets you register one, then shows what exists for that product: a released edition ready to prefill, a draft edition that will prefill once released, or no brochure yet, in which case it offers to create one first. Continuing without a brochure is always available; the step never blocks a protocol.

## The second study: the protocol starts from the brochure

The second protocol for a product is where the shared brochure pays for itself. When it is created, Trelice fills its product facts from the current released edition: names and codes, formulation and storage, mechanism of action, the nonclinical and clinical summaries, dose rationale, overdose management (which the ICH M11 template itself says must be consistent with the brochure), adverse events of special interest, a reference safety line in the adverse events section naming the edition used for expectedness, and a citation of the edition in the reference list. The table below shows where each lands.

The prefill fills empty fields only, unless you ask it to overwrite, respects the protocol’s document standard (fields that exist only in the ICH M11 layout are filled only there) and skips whatever the study type removes. Each filled field stays linked to the brochure section it came from, which is what makes the next section possible. A protocol created before the brochure existed gets the same result on demand with **Import from brochure** in the editor.

Brochure sections and the protocol fields they fill
| Brochure section | Protocol section |
| --- | --- |
| **Title page: product identity and codes** | Title Page and Study Treatments: investigational product, sponsor codes, proprietary and nonproprietary names |
| **Physical, chemical and pharmaceutical properties: formulations** | Study Treatments and Synopsis: dosage form, strength, route, storage and handling |
| **Introduction: mechanism of action** | Background and Rationale: mechanism of action |
| **Summary: nonclinical summary** | Background and Rationale: nonclinical data |
| **Summary: clinical summary** | Background and Rationale: clinical experience |
| **Summary of data and guidance: dose rationale** | Background and Rationale, and the M11 intervention section: dose and regimen rationale |
| **Summary of data and guidance: overdose** | M11 intervention section: overdose management |
| **Summary of data and guidance: adverse events of special interest** | Adverse Events: adverse events of special interest |
| **Reference Safety Information: edition and effective date** | Adverse Events: the reference safety information line used for expectedness |
| **Edition identity** | Reference list: citation of the brochure edition |

## Kept in step both ways

A link between a brochure field and a protocol field is not a one-time copy. When a new edition is released and a linked value changed, every protocol still carrying the old value shows the change beside the field, with three choices. **Take theirs** writes the brochure's value into the protocol through the normal edit path, so review status and amendment rules apply. **Keep mine** records that the difference is intended. **Unlink** stops tracking that one field. A protocol section with an unresolved brochure change cannot be approved until someone has chosen; overdose management and nonclinical findings are not things to discover after approval.

The other direction runs on protocol approval. When a protocol is approved or an amendment is implemented, Trelice assembles the study facts the brochure's clinical experience table needs (study number, title, phase, design, indication, population, countries, planned sample size, regimen and status) and queues them as a proposed update on the product's brochure. Nothing rewrites a released edition: the proposals wait for the brochure's author, who accepts them into the next draft edition or dismisses them with a reason. A later change in the study's status updates the proposal rather than duplicating it.

The brochure is the source of truth for product facts, and the protocols are the source of truth for study facts. Each side proposes, a person decides, and the decision is audited.

## The annual edition without the annual rebuild

Starting a new edition copies the current released one into a draft. The pending updates queued from approved protocols are accepted in bulk, or one by one, into the clinical experience section. The sections that changed are edited and reviewed; the ones that did not are carried forward with their content intact.

The Summary of Changes section is generated, not written. Trelice compares the draft with the edition it supersedes and lists each change by section, with its type, a description, whether it affects the Reference Safety Information, and a rationale the author completes. The edition history accumulates beneath it, and while the draft is being worked on, the superseded edition can be shown read-only beside it, so reviewers see exactly what they are replacing.

A year in which nothing changed still needs a documented review. Each brochure carries a next review date derived from its release date and review cadence; Trelice reminds the owner as it approaches, and **Reviewed, no changes required** records the review in an audited log without opening an edition. The cadence can be aligned with the IND anniversary or the DSUR data lock point.

## Reference Safety Information as a table

The Reference Safety Information (RSI) is the part of the brochure regulators read most closely. Under EU Regulation 536/2014 and the CTFG question-and-answer document that interprets it, the RSI is a clearly identified section listing the expected serious adverse reactions by MedDRA Preferred Term with their frequency and nature: only reactions observed more than once with reasonable evidence of causality, so no class effects, animal-only findings or non-serious reactions. Any change to it is a substantial modification, and the RSI in force when a suspected reaction occurs decides whether it is expected, which is why regulators cite inconsistent RSI as a frequent reason for rejection.

In Trelice the RSI is a structured table rather than prose: one row per expected serious adverse reaction, with the Preferred Term and an optional code, system organ class, frequency category, nature and severity, and notes, plus the RSI version, its effective date and the products or formulations it applies to. Drug Safety is a required reviewer role on the section by default. When a new edition changes the table, the edition is flagged as RSI-affecting, the summary of changes marks the rows, and an RSI changed notice reminds the team that in the EU such a change is a substantial modification.

The protocol side keeps the reference. The adverse events section carries the brochure edition, section and effective date used for expectedness, filled by the prefill and updated when the team takes a new edition's value. Keeping the RSI as rows rather than prose also keeps it checkable: each change to it is itemized in the generated Summary of Changes instead of hiding in a paragraph.

## Section review, roles and signatures

The brochure is authored the way protocols are authored in Trelice. Each section has an assigned writer, due dates and required reviewer roles: nonclinical reviewers on the nonclinical sections, CMC on the formulation section, Drug Safety on the RSI, and a medical expert wherever the organization requires one. Review follows the same configurable workflows and levels as protocols, with the same [approval queue](/docs/approval-queue) and [pending-tasks page](/docs/pending-tasks) (see [setting up review workflows](/docs/review-workflows-and-approvals-setup)).

Every approval, request for changes, withdrawal, release and periodic review is recorded in the permanent [audit trail](/docs/audit-trail) with the deciding user and the time, and releasing an edition is a guarded permission of its own. A released edition is a frozen snapshot with a content hash, so a later export of that edition always prints exactly what was released; the next edition begins as a copy of it.

## How it reaches the downstream documents

The consent form's risks section is where brochure and protocol drift has always shown first. In Trelice, consent risk language draws on the brochure's identified and potential risks and its RSI, through the protocol, and when a new edition changes the guidance or the RSI, the consent forms of every linked study are flagged as stale with a banner naming the edition, so an outdated consent version cannot circulate quietly (see [consent form generation](/downstream-documents#icfs)).

The rest of the chain follows the protocol. The adverse events section's expectedness reference and the reference-list citation travel into the exported protocol. Editions export to Word and PDF with a title page, table of contents and running header naming the product, the edition and its release date, ready to send to investigators and ethics committees. After a release, the **Impact** view answers the question every release raises: it lists every linked study, each protocol with the edition it was prefilled from and any open brochure changes to review, and each consent form flagged for an update, so the follow-through is a worklist rather than a memory exercise.

## Starting from what you already have

Most products already have a brochure, and most organizations already have protocols. When the first protocol for a product exists in Trelice, **New brochure, from a protocol** builds the first edition from it: product identity, formulation, mechanism of action, the background summaries, dose rationale and adverse events of special interest are copied across deterministically into the brochure's structured sections, which become the source of truth for those facts from then on. Nothing is retyped and no AI invents anything.

A brochure can also be authored directly against the outline, section by section, with each section owner filling their own part: nonclinical, CMC, clinical pharmacology, drug safety. AI-assisted import of an existing Word or PDF brochure, on the pattern of [protocol import](/protocol-authoring#protocol-import), is on the roadmap.

## Medical device brochures

A device investigation needs an Investigator's Brochure too, but a different one. ISO 14155 Annex B, MDR Annex XV Chapter II and MDCG 2024-5 set its contents: identification and description of the device (intended purpose, indications, target population, classification, design and materials, software, accessories); the manufacturer's instructions, storage, training requirements and device-specific precautions; the pre-clinical evaluation, from bench testing and biocompatibility to software verification and animal or in-silico studies, with the justification for use in humans; existing clinical data from the literature, prior investigations and post-market surveillance; a risk management summary per ISO 14971 with residual risks, anticipated adverse device effects and reportable device deficiencies; and the regulatory status with the applicable standards.

Trelice ships that outline as a second layout alongside the pharmaceutical one, with its own structured sections for device identification, instructions and training, the pre-clinical evaluation, existing clinical data, risk management and regulatory status. There is no RSI in a device brochure, and none is shown. Editions, review, the summary of changes and the link to device protocols work the same way. Cosmetic studies have no Investigator’s Brochure, since their safety data lives in the Product Information File, so the module does not appear for them.

## Regulatory expectations at a glance

The table below lists what each guidance expects of the brochure and where that expectation is met in Trelice.

Regulatory expectations at a glance
| Guidance | What it expects | Where it lives in Trelice |
| --- | --- | --- |
| **ICH E6(R3) Appendix A** | The brochure’s contents; a title page with edition number, release date and the superseded edition; review at least annually, with revision when significant new information appears; medical expert review | The pharmaceutical layout and its section outline; the edition fields on the title page; the annual review reminder and the reviewed-no-change record; required reviewer roles per section |
| **21 CFR 312.23(a)(5), 312.55 and 312.33** | The five IND elements about the drug; investigators kept informed through revised brochures; each brochure revision described and attached to the IND annual report | The formulation, nonclinical, clinical and guidance sections; exported editions ready to send to investigators; the generated Summary of Changes listing each revision |
| **EU CTR 536/2014 Annex I section D, with the CTFG RSI Q&A** | A brochure per ICH E6 with a clearly identified RSI listing expected serious adverse reactions by MedDRA term; RSI changes are substantial modifications; the RSI in force decides expectedness | The structured RSI table with version and effective date; Drug Safety as required reviewer; the RSI-affecting flag and substantial-modification banner; the protocol’s reference safety line |
| **ICH E2F (DSUR)** | The DSUR uses the RSI in effect at the start of the reporting period; brochure updates aligned with the DSUR schedule | A review cadence that can follow the DSUR data lock point; the RSI changed notice; the structured RSI table with version and effective date |
| **ISO 14155 Annex B, MDR Annex XV and MDCG 2024-5** | Device identification, instructions and training, pre-clinical evaluation, existing clinical data, an ISO 14971 risk summary and regulatory status; no RSI | The device layout with its pre-clinical evaluation, clinical data, risk management and standards sections; the same editions and review |

## Getting started

The Investigator's Brochure is a separate Trelice product that stands on its own: brochure authoring, editions, the generated Summary of Changes, periodic reviews and exports need only the brochure product. The link to protocols (prefill, change tracking and proposed updates) appears when an organization holds both the brochure and protocol authoring products. [Pricing](/pricing) is scoped to your program rather than per seat, so every section owner can be invited.

In the app, start from the investigational product registry: register the product, then create its brochure from the outline, or create it from a protocol once one exists. When a protocol is created for a study that uses the product, the guided step offers the brochure and the prefill. The guides cover each step: [the Investigator’s Brochure](/docs/investigator-brochures), [investigational products](/docs/investigational-products), and [editions and updates](/docs/ib-editions-and-updates).

**Related:** [Protocol authoring](/protocol-authoring)[Downstream documents](/downstream-documents)[Collaboration](/collaboration)[Pricing](/pricing)[Documentation](/docs)

## See it on *your* brochure.

Bring your current Investigator's Brochure and one protocol that uses the product. We will show the prefill, the change tracking and the next edition's summary of changes.

[Book a demo](/contact)