What is it? Why is it important?

The Investigator Brochure (IB):
  • Contains a compilation of an investigational product’s safety data
  • Provides up to date safety data obtained during product development
  • Enables the Site-INV to make an unbiased risk-benefit assessment of a study

In certain circumstances when the IMP or IMD is a marketed product the IB can be replaced by:

  • The Summary of Product Characteristics (SmPC) for marketed MPs:
    • Describes relevant properties of the MP (including safety data)
    • Describes the approved conditions of use
    • Enable healthcare professionals to safely and effectively use the medicine
    • Is also named “Product Information” in Switzerland
  • The Instruction for Use (IFU) for marketed MD:
    • Is provided to users by the MD manufacturer to safely and effectively use the MD
    • Provides information on MD intended purpose, proper use, including any required precautionary measures
    • Contains (among others) a summary of available safety data

More

The IMP/IMD manufacturer performs yearly IB updates. More frequent updates are triggered if new safety relevant information become available from ongoing clinical studies. The IB:

  • Is used for IMPs with no marketing authorisation, or marketed (I)MPs not used in accordance with the terms of its authorisation (e.g. a new route / new dosage / new indication, etc.), or
  • Provides a description regarding the nature, seriousness, and frequency of AEs
  • Provides a cumulative list of expected SARs for IMP (included in the RSI chapter), and foreseeable SAEs and IMD potential risks

The Reference Safety Information (RSI) is a cumulative list of IMPs expected SA(D)R. RSI can be found:

  • In a separate section of the IB
  • In section 4.8 of the SmPC / Product Information (e.g. for marketed MPs used in accordance with its authorisation)

RSI is used by the study SP-INV in order to determine the expectedness of SARs during study conduct (i.e. not used for investigator decision-making during study conduct).

In the event of a SAR occurrence that is not listed in the RSI, then it is classified as unexpected and is thus a SUSAR (e.g. requiring expedited reporting to EC/RA).

Prior to study start, the study relevant RSI is approved by RA.

For IMDs, expectedness of SADE occurring in the study is determined by the SP-INV of the study, based on the list of foreseeable SAEs and potential risks mentioned in:

  • Risk Analysis Report
  • Clinical Investigation Plan (CIP), or
  • IB

What do I need to do?

As a Site-INV:

  • Read the IB, Product information or IFU provided by the SP-INV to familiarize yourself with the safety concerns regarding the product under investigation

As a SP-INV:

  • Ensure to distribute a current and updated IB in due time to participating Site-INV(s) and EC/RA
  • Identify the RSI applicable to your IMP study
  • Use the RSI to assess SARs expectedness, if potentially occurring during study conduct

As a SP-INV manufacturing the product under investigation:

  • Ensure product IB is updated on a yearly basis
  • Initiate more frequent updates in the event any relevant preclinical or clinical safety data become available. The inclusion of a new expected SA(D)R in the RSI, must be accompanied by a risk-benefit assessment of the IMP (e.g. whether its risk is still acceptable). The updated RSI (including the new SA(D)R) should be submitted to RA for approval

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

Reference

ICH GCP E6(R2) – see in particular guideline

  • 7 Investigator’s Brochure

ISO 14155:2020 –Medical device (access liable to costs) – see in particular section

  • 6.5 Investigator’s brochure

MDCG 2020-10 / 1Safety reporting in clinical investigations of medical device under the Regulation (EU)

Swiss Law

FEDLEX – law is available online under number

  • 810.305 ClinO

ClinO – see in particular annex

  • Annex 4 Application dossier and investigator brochure
Abbreviations
  • CIP – Clinical Investigation Plan
  • ClinO - Clinical Trials Ordinance
  • CTU – Clinical Trials Unit
  • EC/RA – Ethic Committee / Regulatory Authorities
  • EU – European Union
  • FEDLEX – Publication Platform for Federal Laws
  • IB – Investigator’s brochure
  • ICH GCP – International Council for Harmonisation Good Clinical Practice
  • IFU – Instructions for Use
  • IMD – Investigational Medical Device
  • IMP – Investigational Medicinal Product
  • ISO – International Organization for Standardization
  • MD – Medical Device
  • MDCG – Medical Device Coordination Group
  • MP – Medicinal Product
  • RA – Regulatory Authorities
  • RSI – Reference Safety Information
  • SADE – Serious Adverse Device Effect
  • SA(D)R – Serious Adverse (Drug) Reaction
  • Site-INV – Site Investigator
  • SmPC - Summary of Product Characteristics
  • SP-INV – Sponsor Investigator
Basic ↦ Safety ↦ Study Information ↦ Investigator Brochure
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Basic ↦ Safety ↦ Study Information ↦ Investigator Brochure

Please note: the Easy-GCS tool is currently under construction.