Human hepatitis B immunoglobulin for intravenous administration: Development, quality control, viral safety, and pharmacokinetics research

INTRODUCTION. Despite the decreasing acute hepatitis B (HBV) incidence due to active vaccine prophylaxis, HBV-specific post-exposure prophylaxis is still a relevant problem for both global and Russian healthcare. Advanced post-exposure prophylaxis, particularly intravenous specific immunoglobulin with its higher bioavailability and fast formation of protective titre, will better protect high-risk groups. Preparations of hepatitis B human immunoglobulins available in Russia are Antigep (Russia) for intravenous administration and Neohepatect (Germany). Enhancing vaccine prophylaxis of hepatitis B and import substitution requires development studies of the first hepatitis B immunoglobulin for intravenous administration produced in Russia.

AIM. This study aimed to develop Russian human HBV immunoglobulin for intravenous administration and perform quality control, safety and pharmacokinetics study.

MATERIALS AND METHODS. Human HBV immunoglobulin (Antigep-Neo) was obtained from the blood plasma of donors with high anti-HBV levels. Antigep-Neo was evaluated according to physico-chemical, biological, and molecular parameters, immunoglobulin A level, activity of the Fc function, and thrombogenic potential. Pharmacokinetic properties were studied in preclinical (rabbit) and clinical (healthy volunteers) studies. Neohepatect and Antigep immuno­globulin preparations were used as comparator drugs.

RESULTS. Production of human antiglobulin is based on the standard Cohn fractionation followed by chromatographic purification and three virus removal and inactivation steps. Antihep-Neo is safe, it contains more than 95% of the human IgG, of them more than 99% are monomers and dimers. The product showed low anticomplementary activity (0.17±0.06 CH₅₀/mg IgG) and low concentration of prekallikrein activator (7.45±2.11 IU/mL) and had no thrombogenic potential. Bioequivalence of Antigep-Neo and Neohepatect was confirmed in preclinical and clinical trials (differences in the pharmacokinetic profiles were not statistically significant).

CONCLUSIONS. The developed human HBV immunoglobulin (Antigep-Neo) meets quality and safety regulatory requirements. Preclinical and clinical studies have confirmed similar pharmacokinetic profile of Antigep-Neo and Neohepatect (comparator).

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