Capacity of the manufacturing process of Flebogamma® DIF, a new human high purity intravenous immunoglobulin, to remove a TSE model-agent

The variant Creutfeldt-Jakob disease (vCJD) is a transmissible spongiform encephalopathy (TSE) associated with the ingestion of cattle derived products affected with bovine spongiform encephalopathy. vCJD emerged in the UK, where most of the cases occurred (170 of 217 cases worldwide). Manufacturers of biological products must investigate the ability of their production processes to remove TSE agents. Two manufacturing steps (polyethylene glycol-PEG precipitation and nanofiltration down to 20 nm) of Flebogamma® DIF, were evaluated by western blot and bioassay to measure the prion protein (PrPSc) and infectivity clearance capacity, respectively. A laboratory scale model representative of the industrial process and a (experimentally) spiked TSE model-agent (hamster scrapie strain 263 K) were employed. Both steps showed a significant capacity to clear the TSE model-agent used since no PrPSc signal or infectivity was detected in the resulting product of each step. PEG precipitation and nanofiltration provided reduction factors of ≥6.19 log10ID50 and ≥5.45 log10ID50 respectively. Both steps showed consistency between western blot and bioassay results. These results demonstrate the ability of the Flebogamma® DIF manufacturing process to clear TSE agents beyond the limit of detection of the assays, by several orders of magnitude.