Investigator’s Brochure (IB)
An Investigator’s Brochure (IB) is a compilation of the clinical and non-clinical data on the investigational medicinal product or products which are relevant to the study of the product(s) in humans.
Chapter 7 of the Good Clinical Practice guideline (CHMP/ICH135/95) describes the requirements for an IB.
The IB shall be updated when new and relevant safety information becomes available, and shall be reviewed by the sponsor at least once per year (CTR article 55.2).
Reference Safety Information
Always indicate in the cover letter where the Reference Safety Information is located.
If the IB is not an SmPC (summary of product characteristics), it shall contain a clearly identifiable section called the ‘Reference Safety Information’ (RSI). The RSI contains an overview of expected Serious Adverse Reactions (SARs). Only SARs included in the approved RSI do not need to be submitted to the EudraVigilance CT module.
For an IMP with a marketing authorization (MA) in the EU, which is used according to the MA, section 4.8 of the SmPC can be used as RSI.
If it is proposed to use an IMP outside the (EU) indication of MA within the trial, section 4.8 of the SmPC for the IMP(s) could only be used as the RSI, if scientifically justified by the sponsor in the clinical trial application cover letter. Otherwise the RSI should always be a clearly separated specific section within the IB.
See further questions 7.7-7.21 of the Q&A CTR. The Q&A also describes what to do in case there are no expected SARs and the conditions for addition of a new SAR to the RSI.