Handling uncertainty in the establishment of a design space for the manufacture of a pharmaceutical product

García‐Muñoz, Salvador; Dolph, Stephanie; Ward, Howard W.

doi:10.1016/j.compchemeng.2010.02.027

Cited by 78 publications

(57 citation statements)

References 27 publications

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“…The process and the effect of the process parameters and their interactions on the product attributes must be understood in detail before process control can be successfully implemented. Therefore, the classical approach to a design space as a set of acceptable ranges for the process parameters is not sufficient, instead a multivariate model is an important tool [5,6]. Mechanistic [7][8][9], empirical [6], and a combination of both mechanical and empirical models [10] have been used for control of batch chromatography processes and proved to successfully compensate for process uncertainty and changes in process requirements.…”

Section: Introductionmentioning

confidence: 99%

Supporting Design and Control of a Reversed‐Phase Chromatography Step by Mechanistic Modeling

Westerberg¹,

Borg²,

Andersson³

et al. 2011

Chem Eng & Technol

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There is a need to design and understand control strategies for biopharmaceutical processes. The control strategy will influence the design space and process performance and should be chosen together with the operating point and design space. Mechanistic modeling is used to design and evaluate control strategies for product pooling in preparative chromatography. A kinetic dispersive model was calibrated to reversed-phase chromatography experiments. Uncorrelated process disturbances were introduced to optimized operating points, and the effects of disturbances were evaluated and reduced by control strategies. Pooling control was implemented at a fixed UV absorbance or as a function of retention volume and UV peak height. The higher flexibility of the second control strategy decreased the loss of yield and productivity caused by the disturbances.

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Section: Introductionmentioning

confidence: 99%

Supporting Design and Control of a Reversed‐Phase Chromatography Step by Mechanistic Modeling

Westerberg¹,

Borg²,

Andersson³

et al. 2011

Chem Eng & Technol

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“…In another example by García-Munoz et al [18], LV models were used to set quality-driven specifications for incoming raw materials. Such specifications accounted for the inherent variability in the process and the combined effect of materials with process conditions onto product quality.…”

Section: Control Strategymentioning

confidence: 99%

An Overview of the Role of Mathematical Models in Implementation of Quality by Design Paradigm for Drug Development and Manufacture

Chatterjee

Moore²,

Nasr

2017

Comprehensive Quality by Design for Pharmaceutical Product Development and Manufacture

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“…The concept "It is important to recognize that quality cannot be tested into products; i.e., quality should be built in by design." was stated in the quality by design initiative (ICH, 2009) and widely accepted in the pharmaceutical manufacturing industry (García-Muñoz et al, 2010;Huang et al, 2010;Prpich et al, 2010;Michaels et al, 2011;Yacoub et al, 2011). Despite previous efforts in evaluating the batch-to-batch consistency of TCM after the production process (Fan et al, 2006;Xie et al, 2008;Tistaert et al, 2011;Wang et al, 2011), there is a greater need to improve the quality consistency of TCM during the manufacturing processes (Huang and Qu, 2011).…”

Section: Introductionmentioning

confidence: 99%

An approach to optimize the batch mixing process for improving the quality consistency of the products made from traditional Chinese medicines

Yan

2013

J. Zhejiang Univ. Sci. B

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Abstract:The efficacy of traditional Chinese medicine (TCM) is based on the combined effects of its constituents. Variation in chemical composition between batches of TCM has always been the deterring factor in achieving consistency in efficacy. The batch mixing process can significantly reduce the batch-to-batch quality variation in TCM extracts by mixing them in a well-designed proportion. However, reducing the quality variation without sacrificing too much of the production efficiency is one of the challenges. Accordingly, an innovative and practical batch mixing method aimed at providing acceptable efficiency for industrial production of TCM products is proposed in this work, which uses a minimum number of batches of extracts to meet the content limits. The important factors affecting the utilization ratio of the extracts (URE) were studied by simulations. The results have shown that URE was affected by the correlation between the contents of constituents, and URE decreased with the increase in the number of targets and the relative standard deviations of the contents. URE could be increased by increasing the number of storage tanks. The results have provided a reference for designing the batch mixing process. The proposed method has possible application value in reducing the quality variation in TCM and providing acceptable production efficiency simultaneously.

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Handling uncertainty in the establishment of a design space for the manufacture of a pharmaceutical product

Cited by 78 publications

References 27 publications

Supporting Design and Control of a Reversed‐Phase Chromatography Step by Mechanistic Modeling

Supporting Design and Control of a Reversed‐Phase Chromatography Step by Mechanistic Modeling

An Overview of the Role of Mathematical Models in Implementation of Quality by Design Paradigm for Drug Development and Manufacture

An approach to optimize the batch mixing process for improving the quality consistency of the products made from traditional Chinese medicines

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