Incorporating random effects in biopharmaceutical control strategies

نویسندگان

چکیده

Abstract Objective Random effects are often neglected when defining the control strategy for a biopharmaceutical process. In this article, we present case study that highlights importance of considering variance introduced by random in calculation proven acceptable ranges (PAR), which form basis strategy. Methods Linear mixed models were used to model relations between process parameters and critical quality attributes set unit operations comprises typical manufacturing Fitting such yields estimates fixed effect sizes as well residual components. To PARs, tolerance intervals specific applied incorporate contribution variance. Results We compared standardized each operation CQA. The results show investigated is not only significant but some even larger than average effect. A comparison ordinary least squares shows neglecting can result PARs too optimistic. Conclusions Uncontrollable week-to-week variability play major role be modelled Following workflow one suggested incorporated into statistically sound strategy, leading lowered out specification reduced patient risk.

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ژورنال

عنوان ژورنال: AAPS Open

سال: 2023

ISSN: ['2364-9534']

DOI: https://doi.org/10.1186/s41120-022-00070-5