摘要
Precipitation is a key manufacturing unit during the immunoglobulin G(IgG)production,which guarantees the quality of the final product.Ethanol is usually used to purify IgG during the precipitation process,so it is important to monitor the ethanol concentration online.Near-infrared(NIR)spectroscopy is a powerful process analytical technology(PAT)which has been proved to be feasible to determine the ethanol concentration during the precipitation process.However,the NIR model is usually established based on the specific process,so a universal model is needed.And the clarity degree of solution will affect the quality of the spectra.Therefore,in this study an integrated NIR system was introduced to establish a universal NIR model which could predict the ethanol concentration online and determine the end-point of the whole process.First,a spectra acquisition device was designed and established in order to get high-quality NIR spectra.Then,a simple prepared ethanol NIR model was constructed to predict the actual manufacturing process.Finally,the end-point was determined to stop the peristaltic pump when the ethanol concentration reached 20%.The results showed that the spectra quality was good,model prediction was accurate,and process monitoring was accurate.In conclusion,all results indicated that the integrated NIR system could be used to monitor the biopharmaceutical process to help us understand the pharmaceutical process.
基金
This work was supported by the National Natural Science Foundation of China(81703403)
the National Key Research and Development Program of China(2019YFC1711200)
the Fundamental Research Funds of Shandong University(2019GN092)
Major Innovation Project of China(2018ZX09201010).
