Project Summary
Heparin is an essential drug, in the form of a complex polysaccharide, which is routinely used in the clinic for
treatment and prevention of thrombosis. About 300,000 doses are administered daily in the United States, and
the worldwide market for heparin is about $7B. Pharmaceutical heparin is purified from pig intestines, sourced
primarily from slaughterhouses in China. With hundreds of millions of slaughtered pigs, the cost of unfractionated
heparin has been extremely low. However, supply chain regulation is difficult, and lead to the heparin crisis in
2007 & 2008 due to economically motivated adulteration of crude heparin. This resulted in over 200 deaths
worldwide. The problem was caused by Blue Ear Disease, decimating Asian pig populations and driving up the
prices. More recently (2019), the African Swine Virus outbreak again decimated Asian pig populations.
Congressional leaders and regulatory agencies continue to be concerned about adulteration and shortages and
our recent experience with pandemics should be a warning that relying on foreign animal populations
for an essential drug is too risky. As an alternative, TEGA has engineered a novel mastocytoma cell line
(MST) to produce recombinant heparin with the same anticoagulant activity as porcine derived heparin. Like
other biologicals, recombinant heparin is produced under completely controlled conditions that significantly
reduces the risks of shortages and provides more consistent products. Higher structural consistency would
reduce the major heparin side effect (bleeding). Through cell engineering, we can also reduce the risk of heparin
induced thrombocytopenia (HIT), perhaps the second most important heparin side effect. Thus, recombinant
heparin would be a premium product in a stratified market aimed at patients undergoing cardiopulmonary bypass
surgery as well as other critical hospital procedures. Optimizing production and reducing cost are critical for
introducing an alternative to porcine heparin. Here, TEGA proposes to collaborate with Sciperio, an advanced
manufacturing company, using their technology to optimize production. Sciperio uses a unique bioreactor design
which facilitates greater control over cell growth and production parameters and actively removes waste
products. Furthermore, these bioreactors can recycle growth factors in a novel process that increases cell
number while reducing cost. Greater control has proven to be especially valuable for alternatives to the standard
production cell types (i.e., CHO, HEK293) which is a direct benefit for the engineered MST cell lines proposed
here. Advances in this area will advance biological manufacturing for applications more complex than antibody
production. The goal of this proposal is to optimize the growth media and growth parameters of our heparin
producing cells in Sciperio’s advanced bioreactor format, increasing the efficiency of production, thus reducing
the cost. This project is directly relevant to the Presidents September 12th Executive Order triggering
biotech as a front in economic competition with China.