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Teaneck, NJ/PRNewswire - GC Biopharma USA announced that a manuscript describing its landmark CEX technology, which removes FXIa from its 10% intravenous immunoglobulin (IVIG) preparation (GC5107), was published in Frontiers in Cardiovascular Medicine. The presence of residual activated coagulation factor XI (FXIa) in IVIG products was identified as the root cause of a small number of thromboembolic events (TEEs) in patients who received IVIG therapy¹ Immunoglobulin (IG) therapy is a mainstay of treatment for patients with primary immunodeficiencies and autoimmune disorders. Numerous licensed IG products formulated for intravenous (IV) or subcutaneous administration are available. While all human IG is manufactured from pooled plasma using variations on the Cohn-Oncley cold ethanol fractionation process, differences in starting material, downstream purification steps, and added stabilizers result in final products that differ in composition in ways that may be very important to individual patients.

Published reports of a small number of TEEs occurring in patients who received high doses of IVIG in the 1990s were attributed to an increase in blood viscosity following infusion or to patient-related factors such as heart disease, renal insufficiency, or prolonged immobilization. Subsequent investigations identified FXIa as a contaminant in some commercial IG preparations. In 2010, an unexpected increase in TEEs associated with using an IVIG product resulted in its temporary removal from the market; residual FXIa was subsequently confirmed to be the root cause².

GC Biopharma USA's rigorous studies have confirmed that a novel 10% IVIG manufacturing process, including CEX chromatography, is a reliable means of removing FXIa from the final preparation. After extensive rounds of testing, including a spiking study to evaluate the capacity of the process to remove high levels of the FXIa protein, the authors have demonstrated that CEX chromatography removes more than 99% of FXIa protein and reduces FXIa activity to below detection limits, even in samples containing 158x greater FXIa levels than that of normal samples. Dr. Jae UK Jeong, Head of R&D, stated, "We are proud to have a world-class team at GC Biopharma focused on developing robust proprietary manufacturing processes for IVIG focused on safety and improved patient outcomes."

It is hoped that this novel proprietary manufacturing process will further support the product's safety—especially for high-risk patients who require IVIG.

Link to Report–Cation Exchange Chromatography Removes FXIa from a 10% Intravenous Immunoglobulin Preparation

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About GC5107
GC5107 is a liquid solution containing 10% immunoglobulin G (100 mg/mL) for intravenous infusion, manufactured from pooled human plasma from US donors. The manufacturing process includes three steps to reduce the risk of virus transmission. These include fractionation, solvent/detergent (S/D) treatment, and nanofiltration.

About Thrombotic Embolic Events (TEE's)
Thrombotic events (TEs) are rare, but often, serious adverse events may occur after administering immune globulin (IG) products.² FXIa was identified as the major biochemical root cause for the increased procoagulant potential and excluded numerous other factors. This underlines the principal importance of FXIa as an inducing factor of thromboembolic events. The clear-cut correlation of enhanced FXIa levels with an overall elevated procoagulant potential can obviously lead to thrombosis, probably dependent on the individual risk factors, which deserve further investigation.¹ As early as 2000, Wolberg and colleagues suggested FXIa in different IVIG brands as a potential reason for an enhanced thrombotic risk during or after IVIG administration.³

About GC Biopharma
GC Biopharma (formerly known as Green Cross Corporation) is a biopharmaceutical company that delivers lifesaving and life-sustaining protein therapeutics and vaccines. Headquartered in Yongin, South Korea, GC Biopharma is a leading global plasma protein and vaccine product manufacturer dedicated to quality healthcare solutions for over half a century.

About GC Biopharma USA, Inc.
GC Biopharma USA, Inc., headquartered in Teaneck, NJ, established its sales, marketing, and business operations in 2018 to serve customers and patients throughout the US. Our foundation is built on the expertise of our parent company, GC Biopharma, a leading biopharmaceutical company delivering plasma therapies and vaccines worldwide. With GC Biopharma USA, Inc., GC Biopharma will further extend its footprint, bringing its expertise and legacy to the United States.

This press release may contain forward-looking statements that express GC Biopharma USA management's current beliefs and expectations. Such statements do not represent any guarantee of future performance by GC Biopharma USA or its management and involve known and unknown risks, uncertainties, and other factors. GC Biopharma USA undertakes no obligation to update or revise any forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rules.

1. Roemisch JR, Kaar W, Zoechling A, Kannicht C, Putz M, Kohla G, et al. Identification of activated FXI as the major biochemical root cause in IVIG batches associated with thromboembolic events. Analytical and experimental approaches resulting in corrective and preventive measures implemented into the Octagam manufacturing process. WebmedCentral Immunother. (2011) 2(6):WMC002002. doi:10.9754/journal.wmc.2011.002002
2. Daniel GW, Menis M, Sridhar G, Scott D, Wallace AE, Ovanesov MV, et al. Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010. Transfusion (2012) 52(10):2113–21. doi:10.1111/j.1537-2995.2012. 03589.x
3. Wolberg AS, Kon RH, Monroe DM, Hoffman M: Coagulation Factor XI is a contaminant in intravenous immunoglobulin preparations. American Journal o f Hematology 2000; 65: 30 34.

GC Biopharma USA Contacts (Media)
Robin Zvonek