Real time flux modelling in biopharmaceutical bioprocessing

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Biopharmaceuticals, such as herceptin (trastumazab) which is used in breast cancer treatment, have revolutionised the treatment of many serious diseases, such as solid tumours, leukaemias, degenerative illnesses such as Alzheimer's, and other diseases having complex contributors, such as asthma. However, in addition to being the most potent drugs humanity has ever deployed, these are also the most complex. This implies lengthy development cycles, and very high costs for therapy. A course of herceptin treatment costs around £27,000 per patient. This has led to serious concerns over access to, and availability of these potent drugs. In order to make these complex agents, specially developed (genetically altered) microbial or animal cell systems (expression systems) are cultured in fermenters or bioreactors. But our understanding of how the interaction of the genetic alterations we introduce, and the fermenter or bioreactor environment we culture the cells within, impact upon the cell metabolism is quite limited, especially in early development phase. This lack of clear knowledge about cell metabolism is one major cause of the long, costly drug development cycle of these agents. Our approach is to focus cutting edge techniques upon achieving better undertsanding of the behaviour of these expression systems early in the development phase. We plan to use non-invasive monitoring techniques (near and mid infrared spectroscopies) actually in the culture vessels together with a previously non real time metabolic analysis tool (flux balancing) to gain real time understanding of the metabolism of these specialised cells when in culture. This technology would give increased knowledge of cell metabolism early in the process cycle, helping accelerate product development, leading to reduced cost therapeutics reaching patients more speedily. This would contribute to increased health in society in general. It would also provide a competitive advantage to the UK biomanuafturing sector involved in making these drugs. In the very near future, this approach could greatly help the development and deployment of specialised cell based therapies ( e.g. stem cells). This is especially important as these agents are even more complex than biopharmaceuticals, and have tremendous potential to contribute to enhancing the health and welfare of society in the immediate future. Achieving