SPECTROSCOPY 57
spectroscopy in pharmaceutical bioprocessing and polystyrene polymerisation processes.
Pharmaceutical bioprocessing Recent successes of biopharmaceuticals and bioprocessing have driven the development of novel therapeutics in the pharmaceutical industry. Recent FDA process analytical technologies (PAT) and quality by design (QbD) initiatives support bioprocessing and emphasise the importance of real-time analysis in the bio/pharmaceutical industry. Real-time analysis of complex bioprocesses must consider many interrelated parameters, all of which need to be optimised. Raman spectroscopy of bioprocesses provides chemically specific data, exhibits excellent model transferability and can be performed continuously and directly in the reaction vessel or consumable. Traditional bioprocess analytics provide general reaction parameters such as temperature, agitation rate, pH and dissolved oxygen levels. Raman can monitor general reaction parameters and data on specific CPPs such as nutrients, metabolite waste production, total cell count and viable cell count. In one representative used
study, Berry et al.2
Raman spectroscopy to analyse a Chinese hamster ovary (CHO) bioprocess at the laboratory (3 L), pilot (200 L), and manufacturing (2,000 L) scales. Raman data from the laboratory, pilot and manufacturing scale were used to develop partial least squares (PLS) prediction models for predicting manufacturing batch output. Tey demonstrate simultaneous measurement of important CPPs at all three scales. PLS predictions of CPPs
correlated closely to externally measured values at all three scales.
Polystyrene polymerisation Polymerisation processes involve monitoring hierarchical phenomena ranging in scale from molecules to reactors. Molecular and rheological properties can significantly affect monomer consumption and bulk polymerisation. As a polymerisation reaction proceeds it is useful to have information from all scales, including the molecular characteristics of the growing macromolecules, the shapes and sizes of colloidal particles, and bulk rheological properties. Method transferability is another important aspect in developing analytical methods for these types of polymerisation reactions in order to ensure that the analytical data can scale with the reaction. Additional considerations are the ability to obtain in-process data without the need to remove samples from the reactor or consumable, and if the spectra provide enough data to ensure a robust analytical method.
Raman spectroscopy
addresses all of these concerns. Brun et al.3
investigated bulk,
emulsion and mini-emulsion polystyrene polymerisation processes and found that rich process information could be generated in all processes. In addition, Raman coupled with rheometry enabled simultaneous real- time monitoring of monomer consumption and reaction medium viscosity, which are important parameters in understanding scale up and gel effect.
Conclusions Raman is a proven technique in the world of process development. Kaiser is at the forefront with its phase- optimised Raman solutions, implementable across all scales, with demonstrated transferability.
For more information ✔ at
www.scientistlive.com/eurolab
Bioreactor processing is analysed for control using the Kaiser Bio-Pro
Lewis, I. R. & Edwards, H. G. M. Handbook of Raman Spectroscopy: From the Research Laboratory to the Process Line. (CRC Press, 2001). 2
REFERENCES: 1
Berry, B., Moretto, J., Matthews, T., Smelko, J. & Wiltberger, K. Cross-scale predictive modeling of CHO cell culture growth and metabolites using Raman spectroscopy and multivariate analysis. Biotechnol. Prog. 31, 566–577 (2015). 3
Karen Esmonde-White is with Kaiser Optical Systems.
www.kosi.com
Brun, N. et al. In situ monitoring of styrene polymerization using Raman spectroscopy. Multi-scale approach of homogeneous and heterogeneous polymerization processes. J. Raman Spectrosc. 44, 909–915 (2013).
www.scientistlive.com
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