A Comparison of Mass and Potency Equated Bovine and Porcine Heparins

Abstract

IntroductionHeparins are extracted from the mast cell rich mammalian tissues such as lung and intestine. While the current source of pharmaceutical grade heparin nationwide is primarily derived from porcine mucosa, bovine mucosal heparins (BMH) are currently being considered by the FDA for re‐introduction in medical and surgical procedures as an alternative to porcine mucosal heparins (PMH). We hypothesized that at USP potency equated levels, bovine and porcine mucosal heparins should be comparable, however at gravimetric concentrations, mass adjusted porcine heparins should exhibit stronger anticoagulant effects in comparison to bovine heparins. The purpose of this study is to compare the clotting profiles and biological properties of mass and USP potency equated BMH and PMH.Materials and MethodPowdered form of pharmaceutical grade heparins of BMH (140 U/mg) and PMH (190 U/mg) origin were obtained from commercial vendors and stock solution was prepared in saline. Powdered protamine sulfate (USP grade) was reconstituted at 1.0 mg/ml in saline. Whole blood thromboelastographic studies were carried out in TEG 5000 Hemostasis system. Clotting (thrombin time; TT and activated partial thromboplastin time; aPTT) and anti‐protease (anti‐Xa and anti‐IIa) assay were measured by using ACL instrument. Relative neutralization by protamine sulfate was carried out at a fixed concentration of 10 ug/ml.ResultsIn whole blood TEG, clotting profile (TT and aPTT) and anti‐protease (anti‐Xa and anti‐IIa), USP potency equated BMH and PMH at concentration range of 0 – 1.0 U/ml showed comparable effects. Protamine sulfate at 10 ug/ml completely neutralized BMH and PMH in in a comparable fashion in clotting profile (TT and aPTT) and anti‐protease (anti‐Xa) while drugs were only partially neutralized in anti‐IIa assay. In mass ratio at 0 – 10 ug/ml, PMH showed strong effects in TEG, anti‐protease (anti‐Xa and anti‐IIa) and clotting profile (TT and aPTT) compare to BMH. BMH and PMH were completely neutralized by protamine sulfate in clotting assay, however in anti‐protease assay BMH was completely neutralized while PMH was only partially neutralized at higher concentrations.ConclusionThese studies suggest that mass porcine heparin exhibits strong effects compared to mass bovine heparin in gravimetric ratios. However, at potency adjusted levels, bovine and porcine heparins exhibit comparable effects sand can be considered biosimilar. These studies conclude that bovine heparin can be an alternative source of heparin to the prominent porcine heparin.