Sheep Mucosal Heparin as a Substitute for Porcine Mucosal Heparin. A Viable Option to Address the Potential Shortage Crisis.

Objective Porcine mucosal heparin (PMH) represents the sole anticoagulant for surgical and interventional procedures along with its medical usage. Sheep mucosal tissue have been used to prepare heparin which demonstrates biosimilar characteristics to PMH. The purpose of this study is to compare multiple batches of sheep mucosal heparin (SMH) with PMH to demonstrate their bio-similarities.

Material and Methods Multiple batches of SMH active pharmaceutical ingredient were obtained commercially (Ronnsi Pharma, Suzhou, China). Multiple batches of PMH were obtained from a supplier (Medefil, Inc, Glendale Heights, IL, USA). Both groups of heparin were evaluated for molecular distribution profile using the HPLC methods and the USP potency using the pharmacopeia approved anti-Xa and IIa methods. The anticoagulant activities were profiled in both the whole blood and plasma based assays. The neutralization of these groups of heparin with platelet factor 4 and protamine sulfate were studied in various assays. The comparative effects of these agents were studied in the HIT antibody mediated aggregation. The antithrombotic and bleeding profiles were measured in standard animal models. The pharmacokinetics and pharmacodynamics profile was investigated in non-human primates after intravenous and subcutaneous administration.

Results Both the SMH and PMH produced comparable molecular weight distribution profiles. The USP potency of the SMH was found to be 190±7 U/ml in comparison to PMH at 181±8 U/ml. In the ACT and TEG, both SMH and PMH produced comparable effects (p>0.05). Both the protamine sulfate and platelet factor 4 produced comparable neutralization of SMH and PMH. In a HIT antibody mediated platelet aggregation assay, no differences were seen in the platelet responses. The bleeding and anti-thrombotic profile of SMH and PMH was comparable. The pharmacokinetic parameters in terms of biologic half-life, volume of distribution, and clearance rate were similar.

Conclusion The results demonstrate that SMH and PMH are comparable in producing their anti-coagulant and anti-protease effects. Moreover their anti-thrombotic and anti-coagulant effects are identical. The PK/PD profile is also comparable for the anti-Xa and anti-IIa effects. These results validate the hypothesis SMH is bio-equivalent to PMH and can be substituted for PMH.

Publication History

Article published online:
18 June 2021