Safety Concern | Rationales and Examples |
---|---|
IIRs or IPRs | Risk Characterization |
• Risk well-characterized; additional information not expected: - Risk of “Severe skin reactions” removed for combination product composed of active substances well-characterized in the meantime • No reasonable expectation that additional PV activities could further characterize the risk: - Risk of “Guillain-Barré syndrome” due to rarity of event • Causal association not supported [IPR]: - Risks of “Congestive Heart Failure” and “Anemia” removed as causal relationship not supported by accumulated scientific and clinical data | |
Risk Management/Minimization | |
• Risk managed by routine RMMs; additional RMMs not required: - Risks of “Hyperglycemia” and “Urinary Tract Infection” removed as fully characterized and appropriately managed through product labels • Management of risk is fully integrated into routine clinical practice: - Risks with published management guidelines removed, e.g. “Lipid Abnormalities” • Risk is a known effect of mature product class: - Risk of “Hypertension” removed, as known to be associated with product class | |
Risk Not Compatible with Regulatory Definitions | |
• Risk not an undesirable clinical outcome: - Risk of “Medication error” removed; clinical consequences of medication errors captured under other IIRs - “Exposure during pregnancy” with no evidence of maternal/infant sequelae; reclassified to MI | |
Othera | |
• Subsuming of risks with the same underlying scientific concept: - Risk of “Opportunistic infections” subsumed under “Serious infections” | |
MI | MI Characterization |
• Adequate safety data available with respect to area of MI: - “Long-term safety” removed as MI once sufficient data available to confirm safety profile with long-term use • No reasonable expectation that additional PV activities could further characterize safety profile within area of MI: - “Use in the elderly” removed as MI where there remains insufficient exposure as condition prevalent in the young | |
MI Not Compatible with Regulatory Definitions | |
• MI not within approved indication: - “Use in pediatric patients” removed for products not authorized in this population - “Use in nursing mothers” removed for products contraindicated in this population | |
• No scientific rationale for different safety profile: - “Use in patients with severe renal/hepatic impairment” removed for products with minimal renal clearance/hepatic metabolism | |
Othera | |
• Concept already covered by IIR/IPR: - “Use in patients with a history of malignancy” removed if malignancy was already listed as an IIR/IPR |