Process analytical technology case study, part III: Calibration monitoring and transfer

Abstract

This is the third of a series of articles detailing the development of near-infrared spectroscopy methods for solid dosage form analysis. Experiments were conducted at the Duquesne University Center for Pharmaceutical Technology to develop a system for continuous calibration monitoring and formulate an appropriate strategy for calibration transfer. Indicators of high-flux noise (noise factor level) and wavelength uncertainty were developed. These measurements, in combination with Hotelling's T(2) and Q residual, are used to continuously monitor instrument performance and model relevance. Four calibration transfer techniques were compared. Three established techniques, finite impulse response filtering, generalized least squares weighting, and piecewise direct standardization were evaluated. A fourth technique, baseline subtraction, was the most effective for calibration transfer. Using as few as 15 transfer samples, predictive capability of the analytical method was maintained across multiple instruments and major instrument maintenance.

Synthetic Calibration for Efficient Method Development: Analysis of Tablet API Concentration by Near-Infrared Spectroscopy

“…Moreover, potential differences in the spectral process signatures [10] for production-and laboratory-scale samples introduce an additional opportunity for prediction error, especially as the laboratory-scale samples will account for the greatest portion of leverage in the calibration dataset. Furthermore, even a well-designed calibration, having controlled variation in many critical factors, can be expected to require periodic maintenance [8,11,12]. While it is straightforward to design a set of tablets covering all degrees of freedom in the space of composition variation, it can be more difficult to anticipate or control the myriad other factors that may impact tablet NIR spectra.…”

“…2). Hence, there is always the possibility that a NIR calibration model may exhibit drift (slope or bias error), thereby, requiring correction or update [12] as process and measurement equipment age, environmental conditions change, or as new batches of raw materials are consumed. Fig.…”

Near Infrared Spectroscopy in Drug Discovery and Development Processes

“…Numerous studies have been carried out to explore the use of NIRS for powder blending control. The fact that NIRS has great potential in this application has been shown by Wargo and Drennen [139][140][141][142]. Cho and co-workers dealt with the effective mass that is sampled by NIR fibre-optic reflectance probes in blending processes and demonstrated that the sampled mass met FDA requirements [143].…”

Chemometrics in Process Analytical Technology (PAT)

“…However, it can also be used in a calibration transfer context, where directions in the data that correspond to instrumental differences are down -weighted. The use of GLS weighting for calibration transfer is discussed in reference [116] .…”