Basic↦Safety↦Safety Information↦Investigator Brochure
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
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 (e.g. IMP=AE; IMD=AE/ADE)
- 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 (e.g. Swissmedic).
Prior to study start, the study relevant RSI is approved by RA (e.g. Swissmedic).
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
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 (e.g. Swissmedic).
- 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
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
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)
ClinO – see in particular annex
- Annex 4 Application dossier and investigator brochure