Heparins Derived from Ovine (Sheep) Mucosa are Interchangeable to their Porcine (Pig) Counterparts

Abstract

Background and PurposeHeparin is the most widely used anticoagulant drug for parenteral indications including surgical, interventional, and medical usage. Currently available heparin is obtained from porcine (pig) intestine. For Muslim countries, an alternate source of heparin, such as ovine (sheep) heparin, from non‐porcine origin may be more acceptable for religious reasons. The purpose of this study is to compare ovine heparin with currently available porcine heparin to demonstrate their biosimilarity.Materials and MethodsSeveral batches of powdered porcine heparin were commercially obtained. Powdered ovine heparins were provided by Ronnsi Pharmaceutical Co., China. These heparins were compared for the anticoagulant (ACT, aPTT, TT), antiprotease (Anti‐Xa, Anti‐IIa), and USP potency cross‐referenced against USP reference heparin. 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 heparins with HIT antibodies were also investigated using HIT antibodies obtained from patients employing platelet aggregation studies. Thrombin generation inhibition studies were also carried out.ResultsThe molecular profile of porcine heparins were comparable and ranged from 15–18 kDA(p<0.05). However, the ovine heparins showed a slightly lower molecular weight in comparison to porcine heparins (14–16 kDA). The anticoagulant activities in all the assays were also comparable for the ovine and porcine heparins. The USP potency of several batches of porcine heparin ranged from 170–200 U/mg (mean=182+/−12) whereas the ovine heparin exhibited 160–210 U/mg (mean=184+/−16) potency (p<0.05). In the ACT studies both the bovine and porcine heparin provided similar results. In the protamine titration curves, both heparin preparations provided superimposable results. Similarly, in the HIT antibody assays, the behavior of ovine and porcine heparin was identical.ConclusionsThese studies clearly demonstrated that the ovine heparins exhibit comparable molecular profiles and anticoagulant activities. Furthermore, in the USP assay, the potency of these preparations were similar. Thus, ovine heparin should be considered biosimilar to its porcine counterpart and is 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.