Application of a Caprylate/Chromatography Purification Process for Production of a Hepatitis B Immune Globulin from Pooled Human Plasma

Background Hepatitis B (HB) is a worldwide public health problem affecting around 250 million people. Only about 10% of people with HB are aware that they are infected. Vaccination is crucial to prophylactically controlling HB and the combination of vaccination and HB immune globulin (HBIG) are essential in preventing disease after exposure to the HB virus. Objectives In this article, a caprylate-chromatography process has been used for the production of HBIG (HBIG-C). The previously used solvent-detergent process produced an HBIG (HBIG-S/D) with an excellent safety profile but allowed the retention of some procoagulant plasma proteins. The present studies were conducted to assess the character and purity of HBIG produced by the caprylate-chromatography process. Design and Methods Several analytical methods (eg, chromatography, immunoassays, and nephelometry) were used to assess the molecular characteristics, purity and HBIG potency and specific activity of HBIG-C. In addition, testing was conducted to assess the levels of several pro-coagulant factors. HBIG-C was compared with HBIG-S/D and other immunoglobulins manufactured by the S/D process. Results The analysis of HBIG-C showed that the product was almost entirely IgG (99.3 ± 0.2% by electrophoresis) and that the residual IgA was less than that found in S/D products. The IgG present in HBIG-C was 99.7 ± 0.6% monomers and dimers as measured by size exclusion chromatography. Aggregates and fragments constituted < 1%. The IgG subclass distribution in HBIG-C was in the normal reference range. Coagulation factor impurities and pro-coagulant activity were reduced in HBIG-C compared to IgG prepared by the S/D method. Conclusions HBIG-C takes advantage of long-established donor selection processes combined with recently improved manufacturing processes to produce a safe and effective HBIG-product. HBIG-C combines high purity with reduced pro-coagulant factors in a product used for post-exposure prophylaxis of HB.