Immunologic Differentiation of Generic Low Molecular Weight Heparins

Low molecular weight heparins (LMWHs) are biological based anticoagulant drugs with a complex heterogeneous structure. Differences in the starting material or manufacturing process compared to that of the original branded product may impart differences in the structure or biologic activity of the final product. We hypothesize that immunologic differences with regard to heparin‐induced thrombocytopenia (HIT) will be evident with generic LMWHs. Generic versions of Lovenox® (enoxaparin sodium; sanofi‐aventis) obtained from Brazil included Enoxalow® (Blausiegel), Heptron® (Cellofarm), and two batches of Versa® (Eurofarma). Their interaction with HIT antibodies was studied using the 14 C‐serotonin release assay (SRA; n=10 platelet donor/HIT sera). The generic LMWHs gave similar activities in the SRA but their interactions with HIT antibodies were stronger than that of branded Lovenox. The observed immunologic differences suggest that although a biological based generic drug might appear similar to the innovator product by mandated regulatory testing, subtle structural variabilities lead to important differences in biological activities that are highly critical for patient safety. LMWHs are not like conventional small molecule pharmaceuticals and require additional assurances for pharmacologic equivalence.