Background and Objectives The outbreak of vCJD in the UK leads to concern regarding the potential for human-to-human transmission of this agent. Plasma-derived products such as albumin, immunoglobulin and coagulation factors were manufactured by BPL from UK plasma up until 1999 when a switch to US plasma was made. In the current study, the capacity of various manufacturing processes that were in use both prior to and after this time to remove the TSE agent was tested.
Materials and Methods Small-scale models of the various product manufacturing steps were developed. Intermediates were spiked with scrapie brain extract and then further processed. Samples were assayed for the abnormal form of prion protein (PrPSC) by Western blotting, and the reduction in the amount of scrapie agent determined.
Results Many of the manufacturing process steps produced significant reduction in the scrapie agent. Particularly effective were steps such as ethanol fractionation, depth filtration, ion-exchange and copper chelate affinity chromatography. Virus retentive filters, of nominal pore size 15 or 20 nm, removed >3 log. The total cumulative reduction capacity for individual products was estimated to range from 7 to 14 log. In the case of factor VIII (8Y), the total removal was limited to 3 log.
Conclusion All the processes showed a substantial capacity to remove the TSE agent. However, this was more limited for the intermediate purity factor VIII 8Y which included fewer manufacturing steps.