Abstract 16653: Bioequivalence of Chemoenzymatically Synthesized Bioengineered Heparin versus Porcine USP Heparins
Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. In an attempt to generate a bioengineered heparin, a biosynthetic pathway was designed that began with bacterial synthesis of the backbone structure. Once extracted from the cell and purified the heparosan polysaccharide undergoes a series of chemoenzymatic modifications to make heparin.
Different batches of bioengineered heparin were synthesized and tested for bioequivalence to USP porcine heparin batches. Bioengineered heparin’s anticoagulant-related activities were determined in vitro for anti-Xa and anti-IIa versus seven different batches of USP heparins as a benchmark using standard chromogenic substrate assays. Additionally, aPTT in comparison to USP heparins was determined using fibrometers and coagulation analyzer. Furthermore, global anticoagulant activities for bioengineered heparin versus USP heparins were evaluated in human blood using thrombelastography (TEG).
Data showed that bioengineered heparin version 4 is bioequivalent to USP heparin and to heparin reference standard in term of anti-X, anti-IIa and anti-Xa/anti-IIa ratios, without any statistically significant differences. Additionally, a comparable dose-response relationships between bioengineered heparin and USP heparins in affecting aPTT and the various clot kinetic parameters (the clot strength, the rate of clot formation, and the lag time to clot initiation) measured by TEG were documented.
These data support the potential in synthesizing a bioequivalent chemoenzymatically bioengineered heparin that is bioequivalent to USP porcine heparin.
- © 2013 by American Heart Association, Inc.