A Comparison of GMP Manufactured Ovine Mucosal Enoxaparin and Branded Porcine Enoxaparin

Objective Low Molecular Weight Heparins (LMWH) such as Enoxaparin are currently derived from porcine mucosal heparin (PMH). The same depolymerization methods that retrieve this enoxaparin from unfractionated heparin can be used from other sources, including from sheep, resulting in ovine enoxaparin. Previous studies have compared non‐good manufacturing practice (GMP) batches of ovine enoxaparin and comparing them to porcine mucosal enoxaparin. The purpose of this study is to compare the pharmacokinetics of GMP ovine mucosal enoxaparin (OME) with that of porcine mucosal enoxaparin (PME). Materials and Methods Branded Enoxaparin (Lovenox, Sanofi‐Aventis, Bridgewater, NJ) and three batches of GMP OME were used. Individual batches of GMP or branded Lovenox were administered subcutaneously (SC) to groups of primates (macaca mulatta) at a dose of 1 mg/kg. Blood samples were collected at baseline and post‐injection times of 2,4, and 6 hours. Plasma samples were frozen for batch analysis. aPTT was measured using clot‐based methods and amidolytic anti‐Xa and anti‐thrombin assays were used to calculate circulating levels of heparin. Individual calibration curves for each the GMP product and branded product were constructed, and the concentrations of drugs were measured at time points in terms of micrograms per milliliter. Drug levels and PK parameters were determined using anti‐Xa and anti‐thrombin assays. The batches of the GMP products were compared among each other and grouped means of all batches were compared with the branded Enoxaparin. Results In the in‐vitro calibration studies, using the aPTT, anti‐Xa and, anti‐IIa assays, despite minor variations, the GMP batches composite values compared well with that of the branded Lovenox. In the PK/PD studies, the three batches of GMP‐produced ovine enoxaparin compared well within the group and the composite mean was similar to that of the branded Lovenox. Discussion At a 1 mg/kg SC dosage, three GMP OME preparations produced comparable anti‐Xa and anti‐IIa effects which were similar to the ones observed with PME. The PK parameters calculated based on this data were also comparable for both groups. It is concluded that the SC pharmacokinetics of the three batches of OME were not only comparable between batches but were also similar to the branded Lovenox. Support or Funding Information None. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .