RESUMO
PURPOSE: The goal of this study is to examine the suitability of in-line infrared measurements to monitor, in real-time, surfactant concentration in the viral vaccine drug substance during a 50KDa tangential flow filtration (TFF) process. METHODS: A ReactIR™ 702L instrument was used to gather spectra of process off-line samples and reference materials to assess the feasibility of monitoring surfactant concentration during a TFF process in real-time. Both univariate and multivariate models were used to evaluate the off-line sample data and were found to be in good agreement with surfactant concentration values obtained by HPLC. These results were used as justification for a real-time TFF experiment with live process material. RESULTS: Small scale ReactIR experiments with process material demonstrated that a multivariate model using the 1300 cm-1 to 1000 cm-1 spectral region can be used to predict surfactant concentrations between TFF exchanges 8 to 15. CONCLUSION: The results of this study demonstrated suitability of an in-line infrared measurement to monitor surfactant concentration in the viral vaccine drug substance between exchanges 8-15 of a 50 kDa tangential flow filtration process. The preliminary multivariate model used for this work can be further optimized for the in-line use at manufacturing scale.
