Journal ArticleDOI
Application of Multivariate Analysis toward Biotech Processes: Case Study of a Cell‐Culture Unit Operation
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TLDR
The feasibility of using multivariate data analysis (MVDA) for supporting some of the key activities that are required for successful manufacturing of biopharmaceutical products is examined, demonstrating the effectiveness of MVDA as a tool for extracting process knowledge.Abstract:
This paper examines the feasibility of using multivariate data analysis (MVDA) for supporting some of the key activities that are required for successful manufacturing of biopharmaceutical products. These activities include scale-up, process comparability, process characterization, and fault diagnosis. Multivariate data analysis and modeling were performed using representative data from small-scale (2 L) and large-scale (2000 L) batches of a cell-culture process. Several input parameters (pCO2, pO2, glucose, pH, lactate, ammonium ions) and output parameters (purity, viable cell density, viability, osmolality) were evaluated in this analysis. Score plots, loadings plots, and VIP plots were utilized for assessing scale-up and comparability of the cell-culture process. Batch control charts were found to be useful for fault diagnosis during routine manufacturing. Finally, observations made from reviewing VIP plots were found to be in agreement with conclusions from process characterization studies demonstrating the effectiveness of MVDA as a tool for extracting process knowledge.read more
Citations
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Journal ArticleDOI
Quality by design for biopharmaceuticals
Anurag S. Rathore,Helen Winkle +1 more
TL;DR: The US Food and Drug Administration's 'quality by design' approach is likely to transform the manufacture of biologics.
Journal ArticleDOI
Roadmap for implementation of quality by design (QbD) for biotechnology products
TL;DR: It is concluded that although several QbD concepts are being practiced by the biotechnology industry, successful dialogue and partnership between the industry and its regulators will be the key to successfulQbD implementation.
Journal ArticleDOI
Process analytical technology (PAT) for biopharmaceutical products.
TL;DR: It is the observation that while significant advances have been accomplished with regard to the ability to analyze/monitor key process and quality attributes in the biotech industry, much more needs to be done with regards to utilizing the collected data for subsequent control of the process, to achieve optimum yield and product quality.
Journal ArticleDOI
Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications.
TL;DR: This two part series addresses PAT as it applies to processes that produce biotech therapeutic products and addresses evolution of the underlying concepts and applications in biopharmaceutical manufacturing.
Journal ArticleDOI
Scale-up analysis for a CHO cell culture process in large-scale bioreactors.
TL;DR: Empirical equations were developed to predict mixing time, oxygen transfer coefficient, and carbon dioxide removal rate under different mixing‐related engineering parameters in the 5,000‐L bioreactors and indicate that increasing bottom air sparging rate is more efficient than increasing power input in improving oxygen transfer andcarbon dioxide removal.
References
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PLS-regression: a basic tool of chemometrics
TL;DR: PLS-regression (PLSR) as mentioned in this paper is the PLS approach in its simplest, and in chemistry and technology, most used form (two-block predictive PLS) is a method for relating two data matrices, X and Y, by a linear multivariate model.
Journal ArticleDOI
Statistical monitoring of multistage, multiphase batch processes
Cenk Undey,Ali Cinar +1 more
TL;DR: In this paper, a framework is proposed for monitoring overall process performance at the end of each batch, where the monitoring of intermediate phases of production is as important as monitoring and control of the final stage.
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Multivariate methods in pharmaceutical applications
TL;DR: This review covers material published within the field of pharmacy in the last five years concerning experimental design, optimization and applications of multivariate techniques, from factorial designs to multivariate data analysis, and the combination of the two in multivariate design.
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Online batch/fed-batch process performance monitoring, quality prediction, and variable-contribution analysis for diagnosis
TL;DR: In this paper, an integrated online multivariate statistical process monitoring (MSPM), quality prediction, and fault diagnosis framework is developed for batch processes, where two different multiway partial least squares (MPLS) models are developed.
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CO(2) in large-scale and high-density CHO cell perfusion culture.
TL;DR: An additional model was developed to predict the effect of bubble size on oxygen and CO2 transfer rates and it is predicted that dissolved oxygen andCO2 levels can be maintained in the range to support maximum productivity in the 500 L reactor.