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). In accordance with paragraphs 10 and 11 of Annex III CTR, the RSI shall contain product information on the investigational medicinal product and on how to determine what adverse reactions are to be considered as expected, and on the frequency and nature of those adverse reactions.
For an IMP with a marketing authorization (MA) in the EU, which is used according to the MA, the RSI should be section 4.8 of the SmPC.
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 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 7.7-7.20 of the Q&A CTR.