Pasteurization of C1 Inactivator in the Presence of Citrate Salts^1,2

Abstract

Conditions have been determined under which the C1 inactivator (C1-INA) can be pasteurized to reduce the risk of transfusion hepatitis associated with its use for replacement therapy in patients with genetic or acquired deficiencies. Recovery of 90% of the biological and immunological activity of a C1-INA concentrate was achieved following heat treatment for 10 h at 60 degrees C in the presence of 3 M potassium citrate. Crossed immunoelectrophoresis in heparinized agarose was used to demonstrate the ability of the pasteurized C1-INA to bind heparin and to form a precipitation pattern with antibody which was almost indistinguishable from that of an unheated control. High pressure liquid chromatography and enhancement of the fluorescence of 1,8-anilinonaphthalene sulfonate were used to show that other proteins present in the concentrate were also stabilized.

Reactivation of C1-Inhibitor Polymers by Denaturation and Gel-Filtration Chromatography

“…However, for C1-inhibitor 6, [31][32][33]. Although of use for clinical concentrates, for research purposes it is not always desirable to have certain other criteria need to be met.…”

Current and emerging biologics for the treatment of hereditary angioedema

“…Starting from the eighties, policies for donors' selection and the introduction of specific manufacturing processes, drastically reduced the risk of viral infection from blood products. Since 1985, different plasmaderived C1-INH (pdC1-INH) preparations were registered in Europe for acute treatment of HAE attacks, and no further evidence of infection related to these preparations has ever been reported [6][7][8][9]. Despite the extended use of pdC1-INH, the first registrative study was published in 2009 [7].…”

“…Since 1985, different plasmaderived C1-INH (pdC1-INH) preparations were registered in Europe for acute treatment of HAE attacks, and no further evidence of infection related to these preparations has ever been reported [6][7][8][9]. Despite the extended use of pdC1-INH, the first registrative study was published in 2009 [7]. It was a randomized, placebo-controlled, double-blind study that compared the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert®, CSL Behring) with placebo in the treatment of single, acute abdominal or facial attacks in patients with HAE.…”

Heat Stability of Lyophilized C1 Inactivator Concentrates

“…Crossed immunoelectrophoresis (CIEP) was carried out as previously described [22], with antiserum to CI-INA (Behring Diagnostics) incorporated in the gel for the second dimension.…”

“…However, in later studies [20, 211, the presence of sucrose was found to significantly reduce the virus inactivation rate during heat treatment. We reported that Cl-INA could withstand pasteurization treatment in the presence of 3 M potassium citrate [22], but a subsequent test using chimpanzees revealed that under these conditions, the HBV was stabilized as well [23].…”