Quantification of clinical mAb solutions using Raman spectroscopy: Macroscopic vs microscopic analysis.

Raman Spectroscopy is well emerged in the field of Analytical Quality Control (AQC) as a rapid and cost-effective technique useful in many applications. The advantage of Raman spectroscopy is the non-invasiveness of measurements that enablesto analyse samples directly in its container. In this study, the potential of Raman spectroscopy was investigated for analysis of clinical preparations of mAbs. Three commercial formulations of monoclonal antibodies (mAbs) Avastin®, Ontruzant® and Tecentriq® corresponding to Bevacizumab (BVC), Trastuzumab (TRS) and Atezolizumab (ATZ) respectively, were analysed in quartz cuvette in macroscopic analysis and through the wall of perfusion bags in microscopic analysis. The spectra have been compared to those of excipients (trehalose and sucrose) and of γ-Globulin, in order to investigate the origin of Raman bands. As expected, Raman spectra were a combination of bands from monoclonal antibodies and correspoding excipients found in formulas. For quantitative analysis of the solutions, models have been constructed using Partial Least Square Regression (PLSR) with Leave K-Out Cross Validation (LKOCV). The quantification performance was comparable for both macroscopic and microscopic analysis, in terms of error and linearity. The results are thus promising for future AQC in situ, in perfusion bags.