Production and chemical processing of low molecular weight heparins.

Heparin is an animal tissue extract that is widely used as an anticoagulant drug. A number of low molecular weight heparins (LMWHs), introduced in the past decade, are beginning to displace pharmaceutical (or compendial) grade heparins as clinical antithrombotic agents. This article describes the chemical properties of the glycosaminoglycan (GAG) heparin and how it is prepared and processed into pharmaceutical grade heparin. There are several commercially produced LMWHs that are prepared through the controlled depolymerization of pharmaceutical grade heparin. The chemistry of the commercial processes used for manufacturing LMWHs is discussed. Structural differences are found in the LMWHs prepared using different commercial processes. Careful control of process variables has generally resulted in the reproducible preparation of LMWHs that are structurally uniform and of high quality. The specifications, however, remain different for each LMWH. Thus, LMWHs are a group of similar but different drug agents. As the structural properties of LMWHs vary significantly, the bio-equivalence or inequivalence of these agents must ultimately be established by the pharmacologists and the clinicians.