Insights into the Purification of C1-esterase Inhibitor from Human Plasma

Abstract

Hereditary angioedema (HAE) is a rare but often life-threatening genetic disorder caused by either lack of or dysfunctional C1-esterase inhibitor (C1-I3NH). C1-INH is a high-cost therapy for HAE. Because plasma-derived C1-INH has a higher half-life than other therapeutics, it may be considered a suitable treatment option for HAE. However, the high cost of plasma-derived C1-INH may make the therapy unaffordable to some patients. Herein, we review the C1-INH purification processes used to date to identify the reasons for the high costs of this therapy and assess the scope of improvements in the purification processes to develop a cost-effective product. A literature search was conducted in PubMed and Google Scholar in January 2023 to identify the relevant articles. The following keywords were used: “C1 esterase inhibitor,” “hereditary angioedema,” and “C1 esterase inhibitor purification from human plasma.” All English-language articles published from 1960 to February 2021 were included. Several plasma products can be purified using the Cohn fractionation process; this decreases the cost of individual products. However, many C1-INH purification strategies developed to date fail to purify other products from the unused plasma fraction (ie, the fraction remaining after C1-INH purification) because of changes in the physical characteristics of the plasma, such as pH and ionic strength; as a result, it is unavailable for the Cohn fractionation process, leading to the high cost of C1-INH. Using cutting-edge purification technologies and more efficient virus removal steps can decrease manufacturing costs, thereby increasing the affordability and safety of the product.