Ultrapure plasma factor VIII produced by anti-FVIIIc immunoaffinity chromatography and solvent/detergent viral inactivation. Characterization of the Method M process and Hemofil M antihemophilic factor (human)

Conclusions

The Method M process was developed to reduce the risk of virus transmission associated with the therapeutic use of AHF products. The Method M process uses a powerful viral inactivation approach and consistently results in a high-purity F VIII preparation. The extent to which F VIII is purified in the Method M process is important in considering the reduction in virus. Protein contaminants such as fibrinogen and fibronectin in the final product provide easily measurable parameters of process efficiency in terms of contaminant reduction. However, it is essential to note that protein contaminant levels in the final product are meaningful only when the steps in the purification process are understood. Precipitation steps and/or ion-exchange steps that reduce protein contamination do not necessarily reflect virus reduction. With the exception of F VIII R∶Ag, which appears to associate specifically with monoclonal-antibody-bound F VIII, all other protein and reagent contaminants are consistently reduced during the immunoaffinity step of the Method M process. Given the extent of viral inactivation that occurs during TNBP/detergent treatment and the extent of contaminant reduction that takes place during the immunoaffinity step, Hemofil M AHF is considered to be substantially safe with respect to viral contamination.