Development of calibration-free/minimal calibration wavelength selection for iterative optimization technology algorithms toward process analytical technology application

Abstract

As continuous manufacturing (CM) processes are developed, process analytical technology (PAT) via NIR spectroscopy has become an integral tool in process monitoring. NIR spectroscopy requires the deployment of complex multivariate models to extract the relevant information. The model of choice for the pharmaceutical industry is Partial Least Squares (PLS). However, the development of PLS can be burdensome due to the time and resource intensive requirements of calibration. To overcome this challenge, calibration-free/minimal calibration approaches have become of increasing interest. Iterative optimization technology (IOT) algorithms are a favorable calibration-free/minimal calibration approach with only the requirement of pure component spectra for successful active pharmaceutical ingredient (API) quantification. IOT algorithms were utilized to monitor potency trends (qualitative) and API content (quantitative) in a CM system and compared to a traditional PLS model. To overcome the reduced prediction performance of IOT during non-steady state conditions, a novel wavelength method based on variable importance in projection scores was employed. Overall, the success and value of IOT algorithms for application in CM settings was demonstrated.

Keywords: Continuous manufacturing; Iterative optimization technology; PAT; PLS; Wavelength selection.