Conference Dates

June 6-11, 2010

Abstract

The scale-up and manufacturing 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 administrated cells may be characterized in terms of their membrane integrity and their surface markers and eventually their biopotency. The challenge is to process the cells at various scales and in a way which maintains these cell properties. Also during formulation the presence of cytokines produced by cells prior to their inactivation is a critical factor. This poster 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 many 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 like cell size, surface phenotype, biopotency and cytokine release were measured. Computational fluid dynamics was used to describe the capillary entry region which allows the cells to be characterized in terms of a critical stress below which there is no significant damage to cell integrity or surface phenotype.

A UK Technology Strategy Board funded program in collaboration with LGC, Nottingham Trent University and originally with Onyvax Ltd.

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