Proton Transfer Reaction – Mass Spectrometry System Monitors GMP Biotech Processes

Ionicon Analytik (Austria) is a partner in the Austrian Center for Industrial Biotechnology (ACIB) for the development of novel tools for real-time process monitoring of biotechnological fermentations. After the successful implementation in a laboratory environment, the Ionicon PTR-technology could now make another important step and has been utilised for real-time process monitoring in an industrial, GMP (Good Manufacturing Practice) controlled fermentation process. The ability to monitor volatile microbial metabolites in the off-gas, without an adaptation to the existing process, has enabled the introduction of PTR-MS (Proton-Transfer-Reaction Mass-Spectrometry) to this highly regulated area.

Modern biopharmaceutical drugs are produced in biotechnological fermentation processes. Monitoring of these processes is becoming increasingly relevant, especially in the manufacturing sector to promote cost-effective production. To date, biotechnical processes are generally monitored using off-line analytical procedures. The disadvantages are considerable time delays between sampling and achieving analytical results – often too late for applying corrective actions. Moreover, most off-line procedures are labor- and therefore cost-intensive. Direct real-time analysis overcome these obstacles and lead to more efficient processes as well as enhanced safety of pharmaceutical products.

A PTR-MS can analyse volatile organic compounds (VOCs) in real-time and in very low concentrations. In a bioreactor, trace amounts of volatile metabolites are emitted as by-products of microbial growth and production. With PTR-MS real-time monitoring of these VOCs in the bioreactor’s off-gas, it is possible to gauge the activity of these micro-organisms and to gain information for a better control of the fermentation process.

 “The advantage of the PTR-MS approach is its non-invasive implementation, where highly relevant process information can be gathered from analysing the fermenter off-gas.”, says Dr. Hubertus Hohenblum from Boehringer Ingelheim, an industrial partner in ACIB. Moreover, the PTR-MS analyser can be placed outside the GMP area. 

For the past few weeks an Ionicon PTR-MS system had been installed at the production site of Boehringer Ingelheim RCV GmbH & Co KG in Vienna. The high quality of the gathered data is proven by highly reproducible results. “This is an additional confirmation that demonstrates the suitability of the PTR-MS approach for large-scale, industrial processes”, says biotech researcher Dr. Rene Gutmann from Ionicon. Furthermore, the fast analysis of Ionicon PTR-MS systems allow for multiplexing to monitoring several fermentations in parallel, which easily justifies the initial investment for these high-tech analysers, which are also available on a lease-to-own basis