LAPSE

LAPSE:2019.1093
Published Article
LAPSE:2019.1093
Robust Process Design in Pharmaceutical Manufacturing under Batch-to-Batch Variation
Xiangzhong Xie, René Schenkendorf
October 26, 2019
Model-based concepts have been proven to be beneficial in pharmaceutical manufacturing, thus contributing to low costs and high quality standards. However, model parameters are derived from imperfect, noisy measurement data, which result in uncertain parameter estimates and sub-optimal process design concepts. In the last two decades, various methods have been proposed for dealing with parameter uncertainties in model-based process design. Most concepts for robustification, however, ignore the batch-to-batch variations that are common in pharmaceutical manufacturing processes. In this work, a probability-box robust process design concept is proposed. Batch-to-batch variations were considered to be imprecise parameter uncertainties, and modeled as probability-boxes accordingly. The point estimate method was combined with the back-off approach for efficient uncertainty propagation and robust process design. The novel robustification concept was applied to a freeze-drying process. Optimal shelf temperature and chamber pressure profiles are presented for the robust process design under batch-to-batch variation.
Keywords
batch-to-batch variation, freeze-drying, parametric probability-box, pharmaceutical manufacturing, point estimate method, robust process design
Suggested Citation
Xie X, Schenkendorf R. Robust Process Design in Pharmaceutical Manufacturing under Batch-to-Batch Variation. (2019). LAPSE:2019.1093
Author Affiliations
Xie X: Institute of Energy and Process Systems Engineering, Technische Universität Braunschweig, Franz-Liszt-Straße 35, 38106 Braunschweig, Germany; Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35a, 3810
Schenkendorf R: Institute of Energy and Process Systems Engineering, Technische Universität Braunschweig, Franz-Liszt-Straße 35, 38106 Braunschweig, Germany; Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35a, 3810 [ORCID]
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Journal Name
Processes
Volume
7
Issue
8
Article Number
E509
Year
2019
Publication Date
2019-08-03
Published Version
ISSN
2227-9717
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Original Submission
Other Meta
PII: pr7080509, Publication Type: Journal Article
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LAPSE:2019.1093
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doi:10.3390/pr7080509
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Oct 26, 2019
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CC BY 4.0
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Oct 26, 2019
 
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Original Submitter
Calvin Tsay
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