Integrated Summary of Safety

The format of the integrated summary of safety is provided in the following outline. 

The adverse experiences reported in the new investigations should be analyzed and displayed as outlined in the integrated summary of safety. If the extent of exposure has increased substantially, the analyses should be performed including both the new data and the data submitted in the NDA. 

Objective 2 entails the assessment of a new drug to determine what types of clinical side effects can be expected and in which patient populations, at what doses and dose durations, and whether the side effects are reversible and, if so, after how long. This knowledge is summarized in the Integrated Summary of Safety (ISS) portion of the NDA/BLA submission and is used by regulatory authorities to decide what should be included in the precautions or warnings sections of the drug label. 

The Commission, in conjunction with the Notice to Applicants Working Party, completed its work on the incorporation of the ICH Common Technical Document (CTD) into a revision of Volume 2B of the Notice to Applicants. A schematic representation of the correspondence between the five modules of the CTD and the four parts of the European registration dossier has also been prepared in order to facilitate the transition from the old application format to the new one. The non-clinical and clinical overviews and summaries are equivalent to the present expert report described above. The clinical summary may replace the Integrated Summary of Efficacy and Integrated Summary of Safety Required by the FDA, and the Clinical Overview and Clinical Summary have been designed to replace the Japanese GAIYO. 

The objective of this PSAP is to provide an outline of the planned analyses for the safety sections of relevant Phase 3 protocols and the Summaries of Clinical Safety (SCSs) and/or Integrated Summaries of Safety (ISSs) for product X, indications A, B, and C. 

Since the PSAP includes planned analyses for individual studies, consideration was given whether the safety section of the SAP for an individual study should simply refer to the PSAP. However, Lilly decided to maintain a full analytical description in the SAP for individual studies. The safety sections in the individual study SAPs generally need more detail to describe the analyses needed for all the phases and more study-specific details (e.g., reference to specific phases) for implementing the analyses. In contrast, a separate SAP for the SCS/integrated summaries of safety (ISS) is not required as the PSAP can serve this need. However, creating a separate SAP for the SCS/ISS is optional. 

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