The occurrence of viral transmission with coagulation factor concentrates treated with a single virus elimination step has resulted in a consensus that multiple virus elimination steps must be incorporated in the processing of these proteins. As an example of this methodology, the steps included in the purification of the factor VIII concentrate Monoclate-P are reviewed and those used to purify the factor IX concentrate Mononine – monoclonal antibody chromatography, sodium thiocyanate incubation, and a novel ultrafiltration system – are described. Rigorous quality control/quality assurance during processing is essential. The ultimate safety of the product used clinically further requires monitoring of long-term stability and verification of the absence of neoantigens that could stimulate unusual levels of antibody formation. Standardization of regulatory compliance will further strengthen the safety of all products. The zeal to add further barriers to viral contamination should not compromise the timely assessment of these additional protections.