• immunoglobulin;
  • IVIG;
  • robustness;
  • TSE;
  • viral safety;
  • virus

Background and Objectives Minimizing the transmission risk of infectious diseases is of primary importance in the manufacture of products derived from human plasma. A novel chromatography-based intravenous immunoglobulin (IGIV) manufacturing process was developed and the reduction of virus and transmissible spongiform encephalopathies (TSE) during the manufacturing process was assessed. Mechanistically distinct steps that could affect virus reduction were identified, and the robustness of virus reduction over the range of process conditions was determined.

Materials and Methods Virus and TSE reduction by processing steps were assessed using a scaled-down version of the IGIV manufacturing process.

Results Virus and TSE reduction at manufacturing process set points were well within safety standards. Robustness studies verified that the reproducibility of virus reduction was maintained at or beyond operating parameter extremes. Virus reduction across two combined manufacturing steps was lower than the sum of virus-reduction values across the individual steps, indicating mechanistic similarity of the two steps with respect to virus reduction. Only reduction from mechanistically distinct steps was claimed.

Conclusions This comprehensive approach to pathogen safety provides the new immunoglobulin manufacturing process with a detailed, yet realistic, assessment of the risk of transmission of infectious pathogens.