Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 21

Pre-marketing: “Unexpected” as applied to clinical trials is defined by FDA in 21CFR312.32(a): An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the investigator brochure or is not listed at the specificity or severity that has been observed, or if an investigator brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the current application, as amended. For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the investigator brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if the investigator brochure listed only cerebral vascular accidents. “Unexpected”, as used in this definition, also refers to AEs or suspected adverse reactions that are mentioned in the investigator brochure as occurring with a class of drugs or as anticipated from the pharmacological properties of the drug, but are not specifically mentioned as occurring with the particular drug under investigation.

Post-approval (Marketed) Products: This takes account of any adverse drug experience that is not included in the current labeling (Package Insert or Summary of Product Characteristics (SmPC)) for the drug product. This includes events that may be symptomatically and pathophysiologically related to an event listed in the labeling, but differ from the event because of greater severity or specificity. FDA provides an example in 21CFR314.80(a): Hepatic necrosis would be unexpected (by virtue of greater severity) if the labeling only referred to elevated hepatic enzymes or hepatitis.

AEs that are considered “class-related” (i.e., allegedly seen with all products in this class of drugs) and are mentioned in the labeling (Package Insert or SmPC) or investigator brochure but are not specifically described as occurring with this product are considered unexpected.