Application of a System Model for Continuous Manufacturing of an Active Pharmaceutical Ingredient in an Industrial Environment

Diab, Samir; Bano, Gabriele; Christodoulou, Charalampos; Hodnett, Neil; Benedetti, Antonio; Andersson, Markus; Zomer, Simeone

doi:10.1007/s12247-021-09609-7

Cited by 8 publications

(2 citation statements)

References 31 publications

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“…This software uses equationoriented flowsheeting. [19][20][21] A one-dimensional tubular onephase plug flow reactor model was selected (see ESI, † section S4). The physical properties (molecular weight, density, physical states) for all the chemical species were inputted into a database (gPROMS FormulatedProducts Utilities 1.0.020190705).…”

Section: Flowsheetmentioning

confidence: 99%

Accelerating reaction modeling using dynamic flow experiments, part 2: development of a digital twin

Silber¹,

Sagmeister²,

Schiller³

et al. 2023

React. Chem. Eng.

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Section: Flowsheetmentioning

confidence: 99%

Accelerating reaction modeling using dynamic flow experiments, part 2: development of a digital twin

Silber¹,

Sagmeister²,

Schiller³

et al. 2023

React. Chem. Eng.

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“…34−37 However, it is potentially of great benefit to use a system model to (a) investigate the impact of multiple process' operating parameters on pharmaceutical product quality with respect to critical impurity content on a mechanistic basis, (b) verify that the considered process space is safely within impurity limits, 38 (c) optimize the manufacturing process with respect to target product quality and process productivity metrics, and (d) assist development in an industrial case study. 39 This study addresses all of these aspects.…”

Section: Introduction 1drug Substance Quality In Pharmaceuticalmentioning

confidence: 99%

Mathematical Modeling and Optimization to Inform Impurity Control in an Industrial Active Pharmaceutical Ingredient Manufacturing Process

Diab

Christodoulou

Taylor

et al. 2022

Org. Process Res. Dev.

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Mathematical modeling of pharmaceutical manufacturing processes can provide insights and understanding regarding the key factors impacting product quality. In this study, we describe the development of a dynamic model for a stage in an active pharmaceutical ingredient (API) manufacturing process, its calibration and validation versus industrial experimental data, and its use to address three objectives: (1) assessment of process operating parameter criticality on key performance indicators (KPIs); (2) confirming whether the considered process operating space safely respected limits of critical quality attribute (CQA) impurities; and(3) finding process setpoints that can potentially improve the KPIs. Objective 1 used global sensitivity analysis (GSA) to find that only operating parameters associated with the reactor were significant. Objectives 2 and 3 used nonlinear optimization, confirming that impurity limits are respected at any point in the considered process operating space and suggesting a shifted process setpoint that could allow enhanced yield (∼4% absolute increase) and reduced impurity content (∼0.5 mol % absolute reduction).

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The Use of Global Sensitivity Analysis to Assess the Oral Absorption of Weakly Basic Compounds: A Case Example of Dipyridamole

Kesharwani,

Louit,

Ibrahim

2024

Pharm Res

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Application of a System Model for Continuous Manufacturing of an Active Pharmaceutical Ingredient in an Industrial Environment

Cited by 8 publications

References 31 publications

Accelerating reaction modeling using dynamic flow experiments, part 2: development of a digital twin

Accelerating reaction modeling using dynamic flow experiments, part 2: development of a digital twin

Mathematical Modeling and Optimization to Inform Impurity Control in an Industrial Active Pharmaceutical Ingredient Manufacturing Process

The Use of Global Sensitivity Analysis to Assess the Oral Absorption of Weakly Basic Compounds: A Case Example of Dipyridamole

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