Office of New Drug Products, OPQ/CDER/FDA, Silver Spring, USA.
Clin Appl Thromb Hemost. 2021 Jan-Dec;27:10760296211052293. doi: 10.1177/10760296211052293.
Heparin is one of the most widely used drugs in the world. It has been described as a lifesaving drug due to its roles in treating many serious diseases and illnesses including kidney dialysis, surgery, cardiac-invasive, heart attack, cardiac arrhythmia, acute coronary syndrome, pulmonary embolism, stroke, deep vein thrombosis, blood clot prevention, and many other related uses. Heparin drug products currently approved in the United States are obtained from porcine intestinal mucosa sourced from pigs, the majority of which is imported from China. However, due to the heparin contamination crisis (2008) and potential shortage and to safeguard the quality of current and future heparin supply chains including raw material, Food and Drug administration (FDA) posted a notification on its website titled "FDA Encourages Reintroduction of Bovine-Sourced Heparin". This perspective is intended to address the history of regulatory and scientific background of heparin drug products obtained from bovine and porcine sources and general recommendations for improving the quality of current heparin manufacturing process including Critical Quality Attributes (CQA), control management, process control, related tests, limits, etc. Additionally, a general plan with systematic steps is proposed for diversifying heparin supply chains by reintroduction of bovine sourced heparin to the US market.
肝素是世界上使用最广泛的药物之一。由于其在治疗许多严重疾病和病症中的作用，包括肾透析、手术、心脏介入、心脏病发作、心律失常、急性冠状动脉综合征、肺栓塞、中风、深静脉血栓形成、预防血栓形成以及许多其他相关用途，肝素被描述为一种救命药物。目前在美国获得批准的肝素药物产品是从猪的肠黏膜中提取的，其中大部分来自中国。然而，由于肝素污染危机（2008 年）以及潜在的短缺问题，为了保障当前和未来肝素供应链的质量，包括原材料，美国食品和药物管理局（FDA）在其网站上发布了一则题为“FDA 鼓励重新引入牛源肝素”的通知。本观点旨在介绍从牛源和猪源获得的肝素药物产品的监管和科学背景历史，并就改进当前肝素生产工艺的质量提出一般性建议，包括关键质量属性（CQA）、控制管理、过程控制、相关测试、限度等。此外，还提出了一个通过重新引入牛源肝素来使肝素供应链多样化的总体计划，并列出了系统性步骤。
