Pathogen safety of human C1 esterase inhibitor concentrate

BACKGROUND: Human plasma-derived products-such as C1 esterase inhibitor (C1-INH) concentrate, used to treat hereditary angioedema-carry with them the risk of transmitting blood-borne viruses and, theoretically, prion proteins. To minimize this risk, three complementary approaches are implemented: selection and testing of plasma donations for the absence of pathogenic blood-borne viruses, similarly testing and releasing the plasma pool for fractionation, and ensuring that the manufacturing process includes validated steps for pathogen inactivation and removal. STUDY DESIGN AND METHODS: This article describes the selection of plasma for the production of C1-INH and the studies used to confirm the pathogen reduction capacity of the manufacturing process: three independent virus reduction steps-pasteurization, hydrophobic interaction chromatography (HIC), and virus filtration-and two prion reduction steps. Samples of product intermediates from the manufacturing steps were spiked with a panel of enveloped and nonenveloped viruses and two prion preparations and subjected to a valid scaled-down version of the respective manufacturing steps resulting in the quantification of the pathogen reduction factors. RESULTS: Validation studies demonstrated overall virus reduction factors for all viruses of more than 15 log, considerably exceeding the potential amount of virus present in a plasma pool for fractionation. Prion proteins were also efficiently removed by the manufacturing process, as currently determined in evaluating the prion removal capacity of the ammonium sulfate precipitation and HIC steps. CONCLUSION: The pathogen reduction capacity demonstrated here indicates that the manufacturing process of the C1-INH Berinert is highly effective for reducing enveloped and nonenveloped viruses and prion proteins.