Heparinox, a generic version of low molecular weight heparin enoxaparin, is bioequivalent to the branded version

Abstract

IntroductionEnoxaparin is the most widely used low molecular weight heparin. Several generic versions of enoxaparin have also become available for clinical use in the indications for which this product is approved. The regulatory bodies require the generic products to conform with the product specifications in terms of biological and structural equivalence. Heparinox (Cristália, São Paulo, Brazil) represents a new generic version of enoxaparin which has become available in the South American continent recently. The purpose of this investigation is to compare the branded enoxaparin (Sanofi Aventis, Paris, France) with heparinox using validated biologic and physico‐chemical assays to demonstrate the similarities of this low molecular weight heparin with its branded version.Materials and methodsHeparinox brand of enoxaparin was obtained in commercial syringes containing 20 and 40 mg doses. Branded enoxaparin was commercially obtained in syringes containing 100 mg. The molecular weight profiling was carried out by gel permeation chromatography using a narrow range calibrator method. The anticoagulant activities were measured in whole blood and plasma based assays. The antiprotease activities were measured using anti‐Xa and IIa chromogenic substrate methods. USP compliant assays were used to calculate potency relative to the NIBSC low molecular weight heparin standard (NIBSC, London, England). Protamine titration studies were carried out to compare the extent of neutralization of the generic and branded products.ResultsThe molecular weight of 2 batches of heparinox was comparable to that of the branded enoxaparin (4.1 kDa vs. 4.1 kDa). In the ACT, APTT and thrombin time assays the concentration curves for heparinox and branded enoxaparin were superimposable. Similarly, the antiprotease activities of the branded and generic products were comparable. There was no difference in the USP potency of the heparinox (96 anti‐Xa units/mg, 32 anti‐IIa units/mg) in comparison to the branded product (97 anti‐Xa units/mg, 32 anti‐IIa units/mg). The protamine titration studies revealed similar neutralization profiles for both the generic and branded products.ConclusionsThese studies demonstrate that the newly introduced generic low molecular weight heparinox exhibits similar molecular weight and functional profiles in comparison to the branded enoxaparin. Additional structural studies using NMR and oligosaccharide analysis, and pharmacological profiling in terms of antithrombotic, bleeding and PK/PD parameters are currently in progress.