Abstract
Purpose: The virus inactivation capacities of the optimised solvent/detergent (S/D) and terminal dry-heat (PermaHeat) treatments, as part of the Wilate® manufacturing process, were determined in this study. Wilate® is a novel, human plasma-derived, VWF/FVIII concentrate, which through the clinical trials has been proven safe and effective in the treatment of von Willebrand disease and haemophilia A patients.
Methods: S/D virus inactivation studies were performed in down-scaled settings using 1% Octoxynol/0.3% TNBP for 4 hours at +23–28°C. PermaHeat was performed at +100°C for 120 min at 0.6% residual moisture in the lyophilisate (0.7–1.6% during regular manufacturing). Robustness conditions were studied for both steps.
Summary of results: S/D treatment revealed the following inactivation ratios [log10]: HIV-1: ≥7.5, SBV: ≥8.6 and PRV: ≥8.5. All enveloped viruses (EV) were inactivated below the detection limits of the infectivity assays already after 2 minutes. Variation of process parameters did not reduce the efficacy of the S/D treatment. For PermaHeat the following inactivation ratios were found at extreme conditions, i.e. low residual moisture [log10]: EV: HIV-1: ≥5.8, SBV: ≥5.5 and PRV: 4.9 - NEV (non-enveloped viruses): REO-3: ≥6.4, HAV: ≥5.7, PPV: 4.1.
Conclusion: The Wilate® manufacturing process comprises two dedicated, efficient and robust virus inactivation steps, S/D and PermaHeat treatments. The total capacities [log10] for the individual viruses amount to ≥13.3 for HIV-1, ≥14.1 for SBV, ≥13.4 for PRV, ≥6.4 for REO-3, ≥5.7 for HAV, and 4.1 for PPV. Other production steps may contribute to virus reduction as well.
