Moisture content determination in an antibody-drug conjugate freeze-dried medicine by near-infrared spectroscopy: A case study for release testing

The use of Near-infrared spectroscopy (NIRS) as a fast and non-destructive technique was employed for moisture content (MC) determination in Antibody-drug conjugates (ADCs) in replacement to Karl Fischer (KF) method. The lab analysis of ADCs, high potent medicines, should be performed in conditions ensuring the operator's safety and using secured analytical tools like NIRS. A NIRS method was first developed and validated in compliance with current guidelines. The novelty of this work first lies in the large number of samples prepared for a wide moisture calibration range of 0.51%-4.01%. Then, the classical Partial Least Square (PLS) regression was used as chemometric tool for the computation of the model. Excellent predictive calibration results were shown. A coefficient of correlation (r) value of 0.99 was obtained. An intercept value of 0.02 and a slope of 0.99 were observed, while the root mean square error of calibration (RMSEC) and the root mean square error of prediction (RMSEP) were respectively 0.10% and 0.12%. In addition, instrumentation, model performances and robustness of the method were evaluated, demonstrating the validation results. Calibration transfer issue and impact of the number of samples were also evaluated. Consequently, a validation strategy was introduced as a basis for submission to the health authorities' for release and stability activities in a cGMP environment in replacement of the KF method. (C) 2016 Elsevier B.V. All rights reserved.