Low Molecular Weight Heparins, Biological Drugs close to Non-Biological Complex Drugs

Low molecular weight heparins (LMWHs) are drug substances widely used as anticoagulants after parenteral administration. They are biological substances obtained from mammalian tissues and they are closely related to non-biological complex drugs because of their heterogeneity and their complex characterization. LMWHs are highly sulfated glycosaminoglycans obtained by partial chemical or enzymatic depolymerization of unfractionated heparin, which is prepared usually by purification from porcine mucosa. Their heterogeneity and polydispersity is the result of the biosynthetic route and of the manufacturing process. Regulatory requirements and control methods are in place in Europe and in the United States to guarantee the quality and safety of these products. LMWHs interfere with the coagulation cascade mainly by interacting through a specific pentasaccharide sequence with antithrombin (AT), and accelerating the inhibition of factor Xa and, to a lesser extent, thrombin (factor IIa). Attempts to produce chemically or enzymatically synthesised LMWHs have not succeeded to displace the currently used LMWH of natural origin.