Enoxaparins Derived from Ovine (Sheep) Tissues are Biosimilar to Branded Enoxaparin of Porcine (Pig) Origin

Abstract

Background and PurposeLow molecular weight heparins (LMWH) are widely used for the management of thrombosis. Enoxaparin represents one of the most widely used LMWH, obtained by depolymerizing porcine (pig) mucosal tissues. Recently, heparin from sheep mucosal tissue has also become available which exhibits a comparable anticoagulant profile to porcine heparin. The purpose of this study is to compare enoxaparin from ovine mucosa with branded enoxaparin.Materials and MethodsFour batches of enoxaparin were commercially obtained (SanofiAventis, Bridgewater, NJ, USA). Four ovine enoxaparins were provided by Ronnsi Pharmaceutical Co., China. These enoxaparins were compared for the anticoagulant (ACT, aPTT, TT), antiprotease (Anti‐Xa, Anti‐IIa), and their potency was cross‐referenced using NIBSC LMWH standard in an amidolytic Anti‐Xa method (Hyphen Biomedical, Paris, France). Molecular profile studies were carried out as specified by U.S. FDA. Protamine titration studies were carried out for both preparations using various tests. The relative interactions of these enoxaparins with HIT antibodies were also investigated using HIT antibodies obtained from patients employing platelet aggregation studies. Thrombin generation inhibition studies were also carried out using a fluorogenic substarte method (Technoclone, Austria)ResultsThe molecular profile of ovine and porcine enoxaparins were comparable and ranged from 4.2–4.5 kDA (p<0.05). The anticoagulant activities in all the assays were also comparable for the ovine and porcine enoxaparins. In the anti‐Xa assays, the NIBSC cross‐referenced potency of several batches of porcine enoxaparin ranged from 98–110 U/mg (mean=102+/−4) whereas the ovine enoxaparin exhibited 102–112U/mg (mean=106+/−6) potency (p<0.05). In the anti‐II assays the potency of the ovine enoxaparins ranged from 25–30 u/ml (mean 28 ± 3) and porcine enoxaparin were 28–35 (mean 31 ± 3). In the protamine titration curves, both enoxaparin preparations provided superimposable results. Similarly, in the HIT antibody assays, the behavior of ovine and porcine enoxaparin was identical.ConclusionsThese studies demonstrated that ovine mucosal tissue‐derived enoxaparin exhibits similar molecular and anticoagulant profiles. In the NIBSC cross‐referenced potency assay, the potency of these preparations were similar. Thus, ovine enoxaparins exhibit comparable profiles when compared to their porcine counterparts and are expected to provide similar results in various clinical indications.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.