Background: For a given plasma-derived product, the risk of final product contamination by hepatitis B virus, hepatitis C virus and human immunodeficiency virus depends upon the epidemiology in the donor population, the virus load in a donation, the product yield and the effective virus reduction capacity in manufacturing. Study Design and Methods: A Monte Carlo simulation model was developed to estimate the risk of virus contamination of a final product resulting from virus contamination of plasma pools for fractionation. The model was run for both source and recovered plasma at various incidence rates for the three viruses to determine virus loads in minipools and fractionation pools resulting from donations with virus levels below test sensitivities. Together with the virus reduction capacity and yield of a theoretical worst case plasma-derived product, the contamination risk in a final vial was calculated. Results: Acceptable upper-bound centre-level incidence rates in the donor population (per donor centre) result in final products with very high margins of virus safety; the largest determinant of these 'Process Limits' is the virus reduction capacity of the manufacturing process. Short donation intervals and long inventory hold periods for source plasma compensates the lower incidence rates typically observed in recovered plasma donors. Conclusions: The model calculates process limits for epidemiological data at collection centres based on an appropriate margin of virus safety for final products. The model also takes into consideration the impact of different donor/donation management systems for source and recovered plasma on the number of low viraemic donations entering the plasma pool for fractionation.
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