Development of a methodology to estimate error in the on-line measurements of blend uniformity in a continuous powder mixing process

Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production

“…Industrial experience indicates that poor measurement performance is often attributable to sampling system issues rather than the process analyzer itself [38]. On-line and in-line measurements may reduce but do not necessarily eliminate sampling errors [39]. Thus, sampling considerations should be assessed.…”

Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20–21, 2014 Continuous Manufacturing Symposium

“…Process analytical technology is “A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in‐process materials and processes with the goal of ensuring final product quality.” There are multiple approaches to ensuring that any particular CQA specification is met:Direct measurement of the CQA,Prediction of the CQA based on a first‐principles model that is fed measurements of related variables and is running in parallel with operations,Prediction of the CQA based on an empirical or semiempirical model (e.g., response surface map, chemometrics model) that is fed measurements of other variables, andOperation of the CPPs to lie within a design space, that is, some specified set shown in offline studies to provide assurance …”

Process Analytical Technology for continuous manufacturing of solid-dosage forms

“…The calibration model was constructed using spectra of flowing powders. In a second paper [12], measurements were again conducted with the help of a chute, but, this time, a multi-point NIR system, equipped with five probes, was mounted above the chute. Multi-point systems have several advantages, such as instrument or process failure diagnostics (by comparing the spectra collected by different probes).…”

“…Another possibility to avoid this would have been to construct five separate models, one for each probe. In this paper [12], the calculations of the amount of spectra, which needed to be averaged in order to be comparable to one unit dose, were also explained extensively.…”

“…Whereas Vanarase et al [12] prepared the calibration samples with a separate batch blender, Martínez et al [13] produced the calibration samples for the construction of a PLS model directly with the continuous blender, which was equipped with two feeders. A PLS model for API quantification was constructed and the influence of changing process parameters was evaluated.…”