15新藥安全藥理學研究及進展(參考版)
2025-01-03 14:37本頁面
【正文】 無明顯影響作用時，應說明濃度選擇范圍 CFDA要求 有關問題 ? 中樞神經系統(tǒng) ：對行為、學習記憶、神經生化、視覺、聽覺和電生理等的影響 ? 心血管系統(tǒng) ：對心輸出量、心肌收縮作用、血管阻力等指標的檢測 ? 呼吸系統(tǒng) ：對氣道阻力、肺動脈壓力、血氣分析等指標的檢測 CFDA要求 追加安全藥理學 ? 泌尿系統(tǒng) ：對腎功能的影響，如對尿量、比重、滲透壓、 pH、電解質平衡、蛋白質、細胞和血生化（如尿素氮、肌酐、蛋白質）等指標的檢測 ? 自主神經系統(tǒng) ：有關受體的結合、體內或體外對激動劑或拮抗劑的功能反應、對自主神經的直接刺激作用和對心血管反應、壓力反射和心率等指標的檢測 CFDA要求 補充安全藥理學 ? 胃腸系統(tǒng) ：觀察藥物對胃腸系統(tǒng)的影響，如胃液分泌量和 pH、胃腸損傷、膽汁分泌、離體回腸收縮、胃液 pH等指標的測定 ? 其它研究 ：潛在的依賴性、骨骼肌、免疫和內分泌功能等的影響 CFDA要求 補充安全藥理學 ?體內血藥濃度低，或其它組織器官分布很少的局部用藥（如皮膚、眼科用藥） ?只用于治療晚期癌癥病人的細胞毒類藥物，在首次用于臨床前可不做一般藥理學研究，但不包括具有新作用機制的此類藥物 CFDA要求 免做安全藥理學 內 容 CFDA安全藥理研究要求 1 ICH安全藥理研究要求 2 安全藥理研究趨勢展望 3 “ Safety pharmacology includes the assessment of effects on vital functions, such as cardiovascular, central nervous system and respiratory systems, and these should be evaluated prior to human exposure.” ICH M3: Nonclinical safety studies for the conduct of human clinical trials for pharmaceuticals. (July 1997) ? Value of safety pharmacology acknowledged by regulators and sponsors ICH要求 ICH Guideline M3, 1997 “ [Safety pharmacology studies] .. investigate the potential for undesirable pharmacological activity in appropriate animal models and, where necessary, to incorporate particular monitoring for these activities in the toxicity studies and/or clinical studies.” “.. these studies may allow for a mechanisticallybased explanation of specific an toxicities, which should be considered carefully with respect to human use and indication(s).” ICH S6 “Preclinical Safety Evaluation of BiotechnologyDerived Pharmaceuticals” (July 1997) ? Pharmacological activity in animals should be considered in toxicology and clinical studies ? Mechanismbased understanding of toxicities (or pharmacological activities) should be carefully considered in the risk assessment ICH要求 ICH Guideline S6, 1997 “ This guidance was developed to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources.” ICH S7A “Safety Pharmacology Studies for Human Pharmaceuticals” (July 2023) ? Safety pharmacology studies have the potential to reduce use of animals and other resources ICH要求 ICH Guideline S7A, 2023 清醒動物 遙測系統(tǒng) ? 檢測清醒狀態(tài)下、自由活動動物的安全藥理學指標 ? 節(jié)省動物 ? 符合動物福利要求 ? 適合不同給藥方式 ? 連續(xù)動態(tài)、長時間檢測指標 ICH要求 Animal ID Compound/Dose Period Dose Period 1 Day 1 Dose Period 2 Day 4 Dose Period 3 Day 8 Dose Period 4 Day 11 L H C M H M L C C L M
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