Structural and functional characterization of low-molecular-weight heparins: impact on the development of guidelines for generic products.

Low-molecular-weight heparins (LMWHs) are poly-pharmacologic drugs used to treat thrombotic and cardiovascular disorders. Recently, several generic versions of branded LMWHs have been introduced. Although generic versions of LMWHs exhibit similar profiles, marked differences in their biological and pharmacologic properties have been demonstrated. Several studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs and also underscore the importance of further pharmacologic studies involving animal and human clinical trials. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) are currently developing guidelines for the acceptance of complex biological drugs including LMWHs. The US FDA considers these drugs as follow-on agents whereas the EMEA classifies these drugs as biosimilar agents. Until clear guidelines are developed, generic interchange of LMWHs may not be feasible.