Applications of Advanced PAT Tools for Biotech Processes

New applications of process analytical measurements in biotech applications can provide immediate benefits through better characterization of process dynamics, earlier identification of process upsets, and enabling process optimization for better yields and production throughput. This poster provides a review of applications of advanced process analytical tools for real-time monitoring of biotech-related processes in research and manufacturing.

Process analytical technology is not a new idea in biotechnology. Within fermentation, for example, measurements of dissolved oxygen, pH, glucose and other key variables are routinely monitored online. These input variables help control cell viability and promote the metabolic pathways leading to the desired product, but non-ideal operation due to the presence of impurities, or fluctuations in temperature and mixing, can cause batch to batch variability resulting in significant deviation from optimum operation. Without a direct measurement of the products – the cells and/or the chemical byproducts – the fermenter is often being driven blind without an opportunity for course correction. As a result, many fermentation processes are operated within a “safe” zone that is far from optimized for production yield and throughput.

A number of application examples will be provided to illustrate the benefits of process analytical technology in the following processes:

o Fermentation:

- Measuring the cell population in real time to monitor cell mass and detect agglomeration in real-time

- In situ monitoring of the production of expressed chemical by-products

o Enzymatic Catalysis:

- Screening and optimization of processes using biocatalysts for hydrolysis and chemical synthesis

o Peptide synthesis and peptide/protein crystallization