LAUSR

Current dramatic developments concerning heparins and related drugs have been the focus of important discussions at several regulatory, clinical, and scientific levels. Unfractionated heparin is the most important of all the glycosaminoglycan drugs, without which, surgical and interventional procedures, hemodialysis, and surface coating of devices would not be possible. A better understanding of glycosaminoglycans has helped further their subsequent development. Heparin is the only anticoagulant with an effective antidote, protamine sulfate. Beyond heparin, related glycosaminoglycans such as sulodexide, hemoclar, and danaparoid are used for a variety of clinical indications. Sulodexide is a blended preparation containing low-molecular-weight heparin (LMWH) and dermatan sulfate as their main active components. Parenteral antithrombin agents such as argatroban and bivalrudin are used for anticoagulation but do not have a reliable antidote. Fondaparinux can be used parenterally but is devoid of any measurable anticoagulant effects in human blood. Ever since its discovery more than 100 years ago, heparin and related drugs have been the focus of scientific and clinical investigations. Advances in technology has provided refinements for the production of heparin and related drugs. In addition, newer technologies including syntheticand biotechnologybased approaches have also been used to produce heparin and related glycosaminoglycans. As polytherapeutic agents, these anticoagulants have other therapeutic properties as well. Lowmolecular-weight heparins are derived from heparin and have been used for thrombotic and cardiovascular indications. The newer oral anticoagulant drugs have gradually replaced the heparins for the long-term management of thrombotic and cardiovascular disorders. However, these drugs have no impact on the use of heparin as an anticoagulant on critically important, and often life-saving, surgical and interventional procedures. Heparin is sourced from the intestinal mucosa of animals, primarily from pigs. Other animals including cows and sheep can also be used for the manufacture of heparin. The 2008 heparin contaminant crisis resulted in a shortage of heparin supply due to regulatory withdrawals and has necessitated steps be taken at various levels to prevent potential future heparin shortages and develop alternate approaches. Imminent risk of a global shortage of heparin caused by the African swine fever afflicting the Chinese pig herd were predicted earlier by the Brazilian investigators. More recently, outbreaks of African swine fever in Europe (Belgium, Bulgaria, Hungary, Latvia, Moldova, Poland, Romania, Russia, and Ukraine) and Asia (China, Cambodia, North Korea, Laos, and Vietnam) have become a major concern. In China, it is estimated that 30% of the swine herd has already been lost and is expected to reach 50% by the end of 2019. This would represent a 25% reduction in the global pig population. The Bulgarian authorities have reported 30 outbreaks in over 10 regions, resulting in 130 000 pigs being slaughtered from a herd of 500 000. Such reductions in herd size will likely result in a shortage of porcine material which is used for the preparation of heparins and will eventually lead to a reduced production of porcine heparin necessitating alternate approaches for anticoagulation methods or alternative sources of heparin material. Concerns over the shortage of porcine heparin have been expressed globally and in particular in the United States where a majority of the heparin used is imported from China. To date, the US Food and Drug Administration (FDA) has not acknowledged the potential impact of the African swine fever outbreak on the heparin supply. Congressional leaders have raised concerns over the outbreak of African swine fever in China’s pig population and its impact on the supply of