Calibration Transfer of a Quantitative Transmission Raman PLS Model: Direct Transfer vs. Global Modeling

Global regulatory agencies have encouraged the use of process analytical technology (PAT) to assure quality in the pharmaceutical industry. A frequently cited obstacle to the implementation of spectroscopy-based PAT methods is the difficulty associated with directly transferring calibration models between PAT instruments. The goal of this study was to compare model transfer strategies for method transfer between two transmission Raman spectroscopy (TRS) instruments. The calibration and test samples were pharmaceutical compacts of acetaminophen and excipients. The experimental design was a 3 factor by 5 level circumscribed central composite design of active pharmaceutical ingredient, lactose, and microcrystalline cellulose concentrations. The calibration and test data were collected using two instruments. Quantitative models were constructed using partial least squares regression. Global calibration modeling and direct model transfer were compared to evaluate opportunities for situations involving method transfer, calibration update, and line extension. Models were compared using a t test-based method to evaluate performance statistics. Statistical analysis demonstrated equivalent performance of the global modeling and direct transfer methods. This work demonstrated that a quantitative transmission Raman model could be directly transferred across instruments, thus avoiding the challenges and resources necessary when creating global models.