Multiplexed Assays for Cell-based Production of Biopharmaceuticals
Material Measurement Laboratory, Biosystems and Biomaterials Division
NIST only participates in the February and August reviews.
The goals of this project are to develop new assays to support the production of safe and effective protein therapeutics. The new generations of biopharmaceuticals are produced using cells in culture. The complex protein products require the correct processing, glycosylation, and three-dimensional folding for effective and safe activity. In addition, the cells used for the production need to be monitored to ensure genetic stability and that contamination by viruses and bacteria do not occur. This requires advanced analytical tools to monitor both the cell substrate and the product. Mammalian cells are used to produce the products at high levels and high density, conditions that result in stress to the cells. To ensure the economic and safe production of biopharmaceuticals requires multiplexed analytical methods that are rapid, reliable, and sensitive. We are developing model cell expression systems based on rodent (Chinese Hamster Ovary Cells) that produce monoclonal antibodies at high levels to study the process and develop new assays. The goals of this project are to develop analytical measurements based on multiplexing using chip arrays, bead based arrays, and conventional flow cytometry. Approaches include protein arrays that will be used to measure the isoforms of the antibody product. Nucleic acid arrays can be used to monitor the genetic stability of the production cells and to detect contamination by viruses and bacteria. Flow cytometry assay can be developed to monitor cell health and signaling pathways