An agile and robust in-line NIR potency deviation detection method for monitoring and control of a continuous direct...

Near Infrared (NIR) method for blend potency estimation has been commonly used as an essential tool for process monitoring and control in continuous manufacturing of solid oral dosage forms. Robustness has been the main challenge for successful application of an NIR method, which often results in a long development time with frequent method update. Robustness deficiency often presents as an offset (bias) on the mean potency estimation. In this paper, the purpose of the NIR method has been redefined from estimating potency to potency deviation. This quantitative approach uses the mean centered potency to estimate potency deviations from the process mean, therefore, detects the non-conforming materials for continuous process monitoring and control. An NIR method was developed at the lab benchtop scale and directly deployed to a direct compression continuous manufacturing platform at Pfizer for mean centered potency estimation. The benchtop calibration provided a speedy and efficient NIR method development and the method showed enhanced robustness for estimating potency deviation in presence of wide process and raw material variations. Integrating with the mean centered approach, the NIR model from the lab could be implemented to different sites using different instruments without requiring model update for the established range of process conditions and raw material properties.