Payne Jessie, Cronin James, Haer Manjit, Krouse Jason, Prosperi William, Drolet-Vives Katherine, Lieve Matthew, Soika Michael, Balmer Matthew, Kirkitadze Marina
Analytical Sciences, Sanofi Pasteur, Toronto, Canada.
Queen's University, Kingston, Canada.
Comput Struct Biotechnol J. 2021 Mar 26;19:1829-1837. doi: 10.1016/j.csbj.2021.03.030. eCollection 2021.
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.
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.
Small scale ReactIR experiments with process material demonstrated that a multivariate model using the 1300 cm to 1000 cm spectral region can be used to predict surfactant concentrations between TFF exchanges 8 to 15.
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.
本研究的目标是检验在线红外测量在50KDa切向流过滤（TFF）过程中实时监测病毒疫苗原料药中表面活性剂浓度的适用性。
使用ReactIR™ 702L仪器收集过程离线样品和参考材料的光谱，以评估在TFF过程中实时监测表面活性剂浓度的可行性。单变量和多变量模型均用于评估离线样品数据，结果发现与通过HPLC获得的表面活性剂浓度值高度一致。这些结果被用作使用实际生产材料进行实时TFF实验的依据。
使用生产材料进行的小规模ReactIR实验表明，使用1300 cm至1000 cm光谱区域的多变量模型可用于预测TFF第8至15次交换之间的表面活性剂浓度。
本研究结果表明，在线红外测量适用于监测50 kDa切向流过滤过程第8 - 15次交换之间病毒疫苗原料药中的表面活性剂浓度。本研究使用的初步多变量模型可在生产规模上进一步优化以用于在线使用。
