VALIDATION OF VIRUS INACTIVATION AND REMOVAL FOR THE MANUFACTURING PROCEDURE OF 2 IMMUNOGLOBULINS AND A 5-PERCENT SERUM-PROTEIN SOLUTION TREATED WITH BETA-PROPIOLACTONE

Abstract. Intravenous immunoglobulins and serum protein solutions are manufactured from human plasma pools of healthy, screened donors. A step-by-step validation of virus removal and/or inactivation was performed for the manufacturing process, which includes cold ethanol fractionation, β-propiolactone (β-PL) treatment, UV irradiation, thermal inactivation and other chemical and physical purification steps. The total viral clearance factors achieved for the entire manufacturing process were by several magnitudes greater than the potential virus load of current plasma pools. Human immunodeficiency virus 1 (HIV-1) infectivity was reduced by >13·4 log for 7S immunoglobulin, >15·3 log for IGM enriched immunoglobulin and > 16 log for a 5% serum protein solution. In addition, high clearance rate for a broad spectrum of model viruses was demonstrated for all three blood derivatives being > 23·2 to > 27·8 log for pseudo rabies virus (PSR), > 12·3 to > 22·6 log for vesicular stomatitis virus (VSV) and 6·9-10·6 log for simian virus 40 (SV40). For the β-propiolactone inactivation step Hepatitis C model viruses, e.g. equine arteritis virus (EAV) and bovine viral diarrhoea virus (BVDV) were also investigated.