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 CH 50 /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).