48 SPECTROSCOPY
Raman’s role in the production line
Karen Esmonde- White on Raman spectroscopy as a process analytical technology for batch or continuous manufacturing
A
n important consideration in successful continuous
or batch manufacturing is integrating analytical tools into the reaction flow. On-line, in- line and at-line analyses enable Quality by Design (QbD) and ensure efficient operations. Raman spectroscopy is uniquely suited for this task and has been proven to: facilitate continuous processing/manufacturing approaches; provide robust method transferability from laboratory to manufacturing; reduce cycle times; and prevent reject product and waste. Scientifically and financially successful Raman applications have been demonstrated at all scales, from at-line in
the laboratory to on-line in manufacturing in PAC and PAT environments. Examples in continuous manufacturing and pharmaceutical reaction control highlight the advantages of in- process Raman spectroscopy.
Continuous manufacturing Tere is a clear need for rugged and validated analytical tools that will meet the specific needs for continuous reaction monitoring. Kaiser Optical Systems’ process Raman solutions feature a fibreoptic technology platform that provides sampling versatility, remote monitoring with excellent scalability and model transferability. Te company’s systems are compatible with microreactor, laboratory, scale- up, and pilot-plant to GMP/ GLP production settings. Tese features can be exploited to control flow processes involving solids or liquids in real time. Two examples illustrate the advantage of Raman spectroscopy in continuous reaction monitoring and controlling continuous solids processing.
Chemical reaction monitoring Kaiser is well versed in monitoring reactions under the intense conditions found in continuous manufacturing within the chemical and petrochemical industries. In one application, Raman spectroscopy was used to measure the continuous reaction between phosphorus and chlorine to produce phosphorus trichloride. Owing to the corrosive intermediates and reaction products, an in-line reaction analysis tool was needed to replace off-line measurements. Raman spectroscopy was chosen because it was able to directly measure all components of interest throughout the reaction, was sensitive to better than 1% for reactants and products and provided fast feedback. Within the pharmaceutical industry, customer applications have demonstrated the practicality of Raman measurements in an etherification reaction and flow synthesis of an oligonucleotide1, 2 In these examples, many benefits were cited, including: reduced
REFERENCES 1
Hart, R. J.; Pedge, N. I.;
Steven, A. R.; Sutcliffe, K. Org. Process Res. Dev. 2015, 19 (1), 196–202. 2
Rydzak, J. W.; White, D.
E.; Airiau, C. Y.; Sterbenz, J. T.; York, B. D.; Clancy, D. J.; Dai, Q. Org. Process Res. Dev. 2015, 19 (1), 203–214. 3
Wasylyk, J.; Wethman,
R. From Development to Plant Implementation of Raman Methods: Strategy, Challenges, and Solutions; Raman Spectroscopy in the Pharmaceutical Industry.
Fig. 1. A PhAT Raman interface for a batch coating (left) and a continuous coater (right)
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