PB0542 - Bio-equivalence of Potency adjusted approved heparin solutions compared to a newly developed heparin solution.

Background: Porcine mucosal heparin solutions with a defined potency adjusted concentrations are widely used for the anticoagulation in medical, surgical and interventional indications. Recently, Sintetica has developed a 20.000 IU (48 ml, 416 IU/ml) solution.

Aims: The purpose of this investigation is to compare the Sintetica heparin solution with other commercially available potency adjusted heparin solutions such as Fresenius, Roche, Hospira and Medefil heparins to demonstrate their bio-equivalence.

Methods: Commercially available heparin solutions were obtained from Sintetica, Roche, Fresenius Kabi, Hospira and Medefil. USP reference standard was obtained from US Pharmacopeia. USP compliant anti-Xa and anti-IIa method based on chromogenic substrate assays. Thrombin generation studies were carried out using a fluorokinetic method (Diagnostico France). The quantification of glycosaminoglycan (GAG) content was made by using a fluorescence probe (Red Probe, Munster, Germany). The clot based assays and amidolytic assays were carried out on ACL Elite analyzer. HIT mediated platelet aggregation studies were carried out using HIT antibodies from clinically diagnosed patient serum. For the potency measurements calibration curves were prepared with the USP standard for cross-referencing.

Results: In the USP compliant anti-Xa and anti-IIa assays all standardized solutions provided comparable results. Similarly in the clot-based assays such as the aPTT, thrombin time, prothrombinase-induced clotting time. All solutions produced comparable anticoagulant effects. Similarly in the thrombin generation assays all products produced comparable inhibitory responses. The HIT antibody mediated platelet aggregation was similar with all solutions. Total GAG content as measured by Red Probe was also comparable.

Conclusion(s): These result demonstrate that commercially available potency adjusted heparin solutions and the newly developed Sintetica heparin solution exhibit comparable anticoagulant and anti-protease effects. Based on these results the Sintetica product is similar to the commercially available clinically approved potency adjusted heparin solutions. Furthermore these results suggest that these solutions are interchangeable for clinical use.