US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins
US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins
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DOI：
10.1007/s11239-012-0680-3
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Fareed, Jawed
中科院分区：
文献类型：
--
作者：
Cohen, Marc;Jeske, Walter P.;Fareed, Jawed
低分子量肝素（LMWH）作为急性冠脉综合征患者的抗血栓治疗，显示出与普通肝素相当或更好的疗效和安全性。每种获批的 LMWH 都是一种多效性生物制剂，具有独特的化学、生物化学、生物物理和生物特性，并表现出不同的药效和药代动力学特性。因此，LMWH 在临床前检测中既不等效，也不在临床功效和安全性方面等效。此前，美国食品和药物管理局 (FDA) 警告不要互换使用各种 LMWH，但最近 FDA 批准了尚未在大型临床试验中进行测试的 LMWH 仿制药。本文重点介绍了 LMWH 制剂之间的生化和药理学差异，这些差异可能导致不同的临床结果，并回顾了当原始/创新药物的仿制药被批准用于临床时医生面临的影响和挑战。
Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic therapy for patients with acute coronary syndromes. Each approved LMWH is a pleotropic biological agent with a unique chemical, biochemical, biophysical and biological profile and displays different pharmacodynamic and pharmacokinetic profiles. As a result, LMWHs are neither equipotent in preclinical assays nor equivalent in terms of their clinical efficacy and safety. Previously, the US Food and Drug Administration (FDA) cautioned against using various LMWHs interchangeably, however recently, the FDA approved generic versions of LMWH that have not been tested in large clinical trials. This paper highlights the bio-chemical and pharmacological differences between the LMWH preparations that may result in different clinical outcomes, and also reviews the implications and challenges physicians face when generic versions of the original/innovator agents are approved for clinical use.