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PTR-MS system monitors GMP biotech processes

IONICON 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 utilized 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 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.

The Austrian Centre of Industrial Biotechnology (ACIB) has dedicated a work package with a task force of academic partners, partners from the biotech industry and analytical device manufacturers. They have implemented and assessed the suitability of several techniques for real-time fermentation-process monitoring.

A PTR-MS can analyze 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. Together with the group of Dr. Gerald Striedner at the University of Natural Resources and Life Sciences (BOKU) in Vienna, IONICON has worked on the implementation of PTR-MS for real-time process monitoring, which was reported earlier. The first step of this implementation has been developed and successfully demonstrated on research-scale bioreactors among several other techniques that have been compared by the researchers.

Industrial fermentation processes are a highly legislated and regulated area following the quality standards laid down in so-called Good Manufacturing Practice (GMP) guidelines. The transfer of a technology that has proven successful in the lab into a GMP process is thus not at all straight forward. Any change to the process, such as the need to install additional probes into the bioreactor, can pose an almost insurmountable obstacle in practice. "The advantage of the PTR-MS approach is its non-invasive implementation, where highly relevant process information can be gathered from analyzing the fermenter off-gas.", says Dr. Hubertus Hohenblum from Boehringer Ingelheim, an industrial partner in the ACIB. The implementation is possible without any changes to the actual process. Moreover, the PTR-MS analyzer can be placed outside the GMP area. Among all evaluated real-time technologies, PTR-MS is the first, and so far the only, that has now made the important step to the "real world".

For the past few weeks an IONICON PTR-MS system had been installed to monitor fermentation processes 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 justify the initial investment of these high-tech analyzers that are also available on a lease-to-own basis.

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Source: IONICON Analytik GmbH