Residual moisture is a key quality control parameter for lyophilized biologicals, as high moisture can correlate with poor stability. Coulometric Karl Fischer titration is the most widely used technology to determine ...Residual moisture is a key quality control parameter for lyophilized biologicals, as high moisture can correlate with poor stability. Coulometric Karl Fischer titration is the most widely used technology to determine residual water content;some chemicals are known to cause problems with Karl Fischer titration, but these chemicals do not usually occur in biologics. Three biological samples, of fibrinogen, heparin and Haemophilus influenza b polysaccharide, have caused particular issue in our hands by routine Karl Fischer analysis, illustrating different limitations with this method. The use of thermogravimetric analysis, with evolved gas mass spectrometric monitoring, is described here as a successful alternative for moisture analysis in these materials.展开更多
As an important process analysis tool,near infrared spectroscopy(NIRS)has been widely used in process monitoring.In the present work,the feasibility of NIRS for monitoring the moisture content of human coagulation fac...As an important process analysis tool,near infrared spectroscopy(NIRS)has been widely used in process monitoring.In the present work,the feasibility of NIRS for monitoring the moisture content of human coagulation factor VIII(FVIII)in freeze-drying process was investigated.A partial least squares regression(PLS-R)model for moisture content determination was built with 88 samples.Different pre-processing methods were explored,and the best method found was standard normal variate(SNV)transformation combined with 1st derivation with Savitzky–Golay(SG)15 point smoothing.Then,four different variable selection methods,including uninformative variable elimination(UVE),interval partial least squares regression(iPLS),competitive adaptive reweighted sampling(CARS)and manual method,were compared for eliminating irrelevant variables,and iPLS was chosen as the best variable selection method.The correlation coe±cient(R),correlation coe±cient of calibration set(Rcal),correlation coefficient of validation set(Rval),root mean square errors of cross-validation(RMSECV)and root mean square errors of prediction(RMSEP)of PLS model were 0.9284,0.9463,0.8890,0.4986% and 0.4514%,respectively.The results showed that the model for moisture content determination has a wide range,good linearity,accuracy and precision.The developed approach was demonstrated to be a potential for monitoring the moisture content of FVIII in freeze-drying process.展开更多
文摘Residual moisture is a key quality control parameter for lyophilized biologicals, as high moisture can correlate with poor stability. Coulometric Karl Fischer titration is the most widely used technology to determine residual water content;some chemicals are known to cause problems with Karl Fischer titration, but these chemicals do not usually occur in biologics. Three biological samples, of fibrinogen, heparin and Haemophilus influenza b polysaccharide, have caused particular issue in our hands by routine Karl Fischer analysis, illustrating different limitations with this method. The use of thermogravimetric analysis, with evolved gas mass spectrometric monitoring, is described here as a successful alternative for moisture analysis in these materials.
基金We are grateful for the financial support of the Major Special Project of National Science and Technology (No.2014ZX09508003).
文摘As an important process analysis tool,near infrared spectroscopy(NIRS)has been widely used in process monitoring.In the present work,the feasibility of NIRS for monitoring the moisture content of human coagulation factor VIII(FVIII)in freeze-drying process was investigated.A partial least squares regression(PLS-R)model for moisture content determination was built with 88 samples.Different pre-processing methods were explored,and the best method found was standard normal variate(SNV)transformation combined with 1st derivation with Savitzky–Golay(SG)15 point smoothing.Then,four different variable selection methods,including uninformative variable elimination(UVE),interval partial least squares regression(iPLS),competitive adaptive reweighted sampling(CARS)and manual method,were compared for eliminating irrelevant variables,and iPLS was chosen as the best variable selection method.The correlation coe±cient(R),correlation coe±cient of calibration set(Rcal),correlation coefficient of validation set(Rval),root mean square errors of cross-validation(RMSECV)and root mean square errors of prediction(RMSEP)of PLS model were 0.9284,0.9463,0.8890,0.4986% and 0.4514%,respectively.The results showed that the model for moisture content determination has a wide range,good linearity,accuracy and precision.The developed approach was demonstrated to be a potential for monitoring the moisture content of FVIII in freeze-drying process.
