Multiblock PLS analysis of an industrial pharmaceutical process.

Abstract:

:The performance of an industrial pharmaceutical process (production of an active pharmaceutical ingredient by fermentation, API) was modeled by multiblock partial least squares (MBPLS). The most important process stages are inoculum production and API production fermentation. Thirty batches (runs) were produced according to an experimental planning. Rather than merging all these data into a single block of independent variables (as in ordinary PLS), four data blocks were used separately (manipulated and quality variables for each process stage). With the multiblock approach it was possible to calculate weights and scores for each independent block. It was found that the inoculum quality variables were highly correlated with API production for nominal fermentations. For the nonnominal fermentations, the manipulations of the fermentation stage explained the amount of API obtained (especially the pH and biomass concentration). Based on the above process analysis it was possible to select a smaller set of variables with which a new model was built. The amount of variance predicted of the final API concentration (cross-validation) for this model was 82.4%. The advantage of the multiblock model over the standard PLS model is that the contributions of the two main process stages to the API volumetric productivity were determined.

journal_name

Biotechnol Bioeng

authors

Lopes JA,Menezes JC,Westerhuis JA,Smilde AK

doi

10.1002/bit.10382

subject

Has Abstract

pub_date

2002-11-20 00:00:00

pages

419-27

issue

4

eissn

0006-3592

issn

1097-0290

journal_volume

80

pub_type

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