Hottinger Michelle, Liang Bryan A
Institute of Health Law Studies, California Western School of Law, USA.
Am J Law Med. 2012;38(4):667-89. doi: 10.1177/009885881203800403.
Generic drugs represent a significant portion of the medical arsenal in treating disease. As copies of originator drugs, these drugs have been permitted abbreviated approval under the Hatch-Waxman Act. Yet with the current cost focus upon generic formulations, potential safety issues with generics have arisen. Although there is an established criterion of "bioequivalence" that generic formulations must demonstrate, narrow-therapeutic index drugs for sensitive clinical circumstances such as epilepsy, antiplatelet therapies, and mental health treatments may require different regulatory treatment than other generic drugs. Further, in these circumstances, differences in generic formulations may lead to adverse clinical outcomes due to less stringent bioequivalence tolerances. Yet there is no mandate for comparison between different generic formulations. Countries outside the United States advocate for narrowing tolerance ranges for these high risk health situations and the drugs for their treatment. We argue in this paper that additional patient safety matters must be taken into account for narrow therapeutic disease drugs, and regulatory bodies should emphasize greater tightness in bioequivalence before these narrow-therapeutic drug generic formulations are approved.
仿制药在治疗疾病的药物储备中占很大比例。作为原创药物的复制品，这些药物已根据《哈奇-沃克斯曼法案》获得简化审批。然而，鉴于目前对仿制药制剂成本的关注，仿制药的潜在安全问题已经出现。尽管存在仿制药制剂必须证明的“生物等效性”既定标准，但对于癫痫、抗血小板治疗和心理健康治疗等敏感临床情况的窄治疗指数药物，可能需要与其他仿制药不同的监管处理。此外，在这些情况下，由于生物等效性耐受性不那么严格，仿制药制剂的差异可能导致不良临床结果。然而，对于不同仿制药制剂之间的比较并没有要求。美国以外的国家主张缩小这些高风险健康状况及其治疗药物的耐受性范围。我们在本文中认为，对于窄治疗疾病药物，必须考虑额外的患者安全问题，监管机构在批准这些窄治疗药物的仿制药制剂之前应强调生物等效性方面更严格的要求。
