Acosta Martinez, J.P.; (2011) Bioprocessing of human cells for vaccines and other cell therapies. Doctoral thesis, UCL (University College London).
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The scale-up and manufacture of therapies based on intact whole cells presents a major challenge for development scientists and engineers due to the stress-reactive nature of these cells. The administered cells may be characterized in terms of their membrane integrity, size, surface markers and eventually their biopotency. The challenge is to process the cells at various scales and in ways which maintain these cell properties. Also during formulation the presence of cytokines produced by cells is a critical factor. This study presents an approach to allow the rapid characterization of human cell lines in terms of their resistance to hydrodynamic stress. An ultra scale-down method has been developed which allows investigation with small quantities of cells commonly available at the early discovery stage. The study describes controlled flow through a capillary device where cells are exposed to several defined hydrodynamic stresses. A Design of Experiments approach was used to understand the combined effect of process parameters such as flow rate, length of capillary and number of passes. This was followed by an additional set of detailed ultra scale-down experiments where other critical quality attributes such as cell size, surface phenotype, biopotency and cytokine release were measured. Computational fluid dynamics was used to describe the capillary entry region. The cells were then characterized in terms of a critical stress below which there is no significant damage to their integrity. The results were used to predict successfully a capillary design where no damage would occur at a specified high flow rate; for example as required for cell dispensing or vialling operations. Equally, the extent of loss of cell integrity was also successfully predicted in a capillary flow system designed to yield high levels of break up.
|Title:||Bioprocessing of human cells for vaccines and other cell therapies|
|Additional information:||This thesis can not be made available as it contains confidential material|
|UCL classification:||UCL > School of BEAMS > Faculty of Engineering Science > Biochemical Engineering > Advanced Centre for Biochemical Engineering|
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