Fig. 6
From: An industrial case study: QbD to accelerate time-to-market of a drug product
Definition of the operational ranges for UO2 and UO6 using PCA modelling and computer simulations. Top left panel (A): PCA score plot of the analysis of 9 compliant manufactured batches (green dots). The data set consists of the CPPs values measured for UO2 and UO6; the score plot represents the first two principal components (PC1 and PC2), which describe 53.7% and 21.7% of the variance in the data, respectively. The dashed line corresponds to the 95% confidence ellipse for the model scores. The red dot shows the model predicted scores for a non-compliant production batch. The blue outlined rectangle that covers only compliant batches defines a first estimate of UO2 and UO6 design space (DS). Top right panel (B): PCA model projections for two different sets of batch simulation runs (100,000 samples per run) made to refine the acceptable ranges for UO2 and UO6 CPPs. Each small point corresponds to the predicted model scores for a simulated batch (sample) that has been generated by considering random combinations of the CPPs values within a predefined admissible range (see text for further details). Predicted scores were projected onto the original score plot shown in panel A. The blue outlined rectangle represents the first DS estimate, as defined in panel A, and was used as an acceptance criterion for model predicted scores together with other two diagnostic statistics (Hotelling’s T2 and sum of squared residuals). The small red and green dots correspond to a set of simulations made after a first refinement of the admissible values for CPPs, where simulated samples satisfying all the acceptance criteria are shown in green. The small blue dots represent the model outcomes for a final set of simulations made after a second (and final) refinement of the CPPs ranges, whereby all simulated batches were found to comply with the predefined acceptance criteria. Bottom panel (C): The table summarizes the initial experimental ranges of the manufactured compliant batches (orange) and the final restricted ranges (blue) obtained for each CPP of UO2 and UO6 based on the described methodology