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Background: Viral safety is of paramount importance for human plasma-derived therapeutic proteins. Recent reports of blood-associated transmission and continuous regional outbreaks of dengue fever have prompted a validation of clearance of dengue virus in the manufacture processes of the plasma-derived products., Study Design and Methods: A high titer of cultured dengue virus serotype 2 was spiked into process samples before individual steps of albumin and immunoglobulin manufacture processes, including cold ethanol precipitation, cation-exchange chromatography, pasteurization, solvent/detergent treatment, and virus filtration. Clearance of dengue virus was quantified with TCID(50) assays in the culture of Vero E6 cells and, when appropriate, real-time polymerase chain reaction (RT-PCR) assays., Results: The individual process steps were all effective in the inactivation and/or removal of dengue virus, and the data obtained clearly demonstrate that the risk of dengue virus transmission was reduced cumulatively by at least 10.12 and at least 14.24 log in the albumin and immunoglobulin manufacture processes, respectively., Conclusion: The dedicated viral inactivation and/or removal approaches currently implemented in the manufacture of plasma-derived products provide a good safety margin with regard to the transmission of dengue virus.

Background: Severe acute respiratory syndrome (SARS) is a new infectious disease caused by the SARS virus. Current first-line treatments are experimental, and their effectiveness remains open to question. For more effective treatment and prevention of SARS, human SARS hyperimmune globulins for intravenous (IV) injection were purified in this study., Study Design and Methods: A combination of cold ethanol precipitation and ion-exchange chromatography was used to process pooled SARS convalescent plasma samples. Virus inactivation and removal approaches were taken to ensure safety., Results: The purified hyperimmune globulins were formulated as a 5 percent solution, with an antibody titer specifically against the SARS virus of 1:83, 1:1600, and 1:200, as determined by enzyme-linked immunosorbent assay, immunofluorescence assay, and neutralizing antibody test, respectively. The purity of the SARS hyperimmune globulins was 99.0 percent, and the monomer and dimer content was 100 percent. Other variables analyzed met the Chinese Requirements of Biologics for IV immune globulin. The SARS hyperimmune globulins prepared were subsequently approved for clinical evaluation by the Chinese National Institute for the Control of Pharmaceutical & Biological Products., Conclusion: IV-injectable, purified, and concentrated human SARS hyperimmune globulins were prepared from pooled convalescent plasma samples, which are ready to be further evaluated.