CERSI P.I.s and Collaborators: William E. Bentley, Ph.D., University of Maryland, Robert E. Fischell Institute for Biomedical Devices, Gregory F. Payne Ph.D., UMD, Institute for Bioscience and Biotechnology Research
FDA SME and Collaborator: Carole Sourbier, Ph.D., CDER, FDA
The vast majority of biopharmaceuticals in the market today are monoclonal antibodies and their efficacy relies on the antibody’s ability to bind to antigens including infectious agents, cancer receptors, etc. These antibody drugs are synthesized by genetically engineered mammalian (Chinese hamster ovary, CHO) cells and cultivating these cells in large bioreactors. The development of the production process and the manufacturing operations have great influence on the yield of antibody and its quality. Process variables such as pH, dissolved oxygen level, and nutrient levels in the reactor fluids can lead to highly productive living cells producing high quality product or the opposite, the generation of low yielding cells that produce damaged antibodies. This project addresses the need for rapid, scalable, and informative analytical measurements that report on the processing conditions in these reactors. The method, “mediated electrochemical probing (MEP)” was pioneered by our groups over the last five years and there is widespread interest within the biomanufacturing industry for its use. We have built a robust sensor and gained new insight on a variety of samples, including those of relevance to the FDA: amino acids, cell culture media, and cells. MEP enables rapid, low cost, electrochemical measurement of raw materials, cell growth, and product formation. The data obtained is rich and informative. We will use MEP to interrogate CHO cell cultures, linking its measurements to cell growth and productivity data.
We have newly constructed an “autonomous redox discovery platform (ARDP)” device that uses both electrochemical and spectroscopic measurements to reveal electrochemical characteristics of various samples. Specifically, the method analyzes the extent of oxidation of the proteins, lipids, and media components in a sample, and the damage oxidation might cause to the antibody products. The method incorporates complex time-varied voltage inputs and signal processing to obtain data rich outputs. The measurements are rapid, informative, and require little to no sample preparation. In this project, we will trace the metabolic activity of CHO cells grown in industry-standard growth media. We will correlate MEP measurements with growth, viability, and productivity. Cultures will be exposed to mild stresses to characterize how these mild stresses are detected by the ARDP. Stresses can include ammonia, temperature, pH, dissolved carbon dioxide (pCO2), dissolved oxygen (DO), glucose, osmolarity, and lactate. With these data in hand, industry practitioners and regulators can more easily ensure that antibody therapeutics are generated using safe and reproducible production methods.