In upstream bioprocessing, the product is the process. Having a consistently high-quality process means that the product’s Critical Quality Attributes (CQA’s) are consistently achieved, and the process is at an optimal percent yield. Consistently achieving these goals used to be an extraordinary challenge because traditional offline laboratory measurements could not provide an around-the-clock understanding of important cell metabolic parameters such as glucose, lactate, ammonia and amino acids.
The suboptimal feed strategies based on a single daily offline measurement resulted in inconsistent product quality, process excursions and lost batches. Moreover, the daily task of manually pulling samples from the bioreactor increased contamination risk which was not optimal for time allocation and timely responses to process upsets. The industry soon turned to inline measurements to address these issues.
Endress+Hauser: An early partner in delivering innovation
Since 2011, Endress+Hauser’s Raman has been at the forefront of inline Raman spectroscopy in upstream bioprocessing. It provides a multi-parameter measurement with a single inline probe that gives 24/7 transparency into the cell culture or fermentation bioprocess. Raman spectroscopy uses optical scattering to give a “molecular fingerprint” of the measured sample and is compatible with bioreactors from the micro-scale to clinical manufacturing. This molecular fingerprint can be used to measure critical process parameters such as glucose, lactate, amino acids, viable cell density and ammonia. Our customers have seen successes in improved yield, cross-scale transfer, faster process development times and advanced feed strategies.
Looking for more technical details on these studies?
Check out our 2016 and 2022 review papers to learn how the industry is using Endress+Hauser’s Raman spectroscopy, powered by Kaiser Raman technology, to achieve application and industry success in cell culture bioprocesses.
Let’s look at an illustrative example in fermentation to complement the review papers in cell culture. For one biopharmaceutical manufacturer, it was estimated that after just 35 fermentation batches, the cost of transitioning to and operating an inline Raman analysis solution was more than covered by the savings of eliminating offline tests. Additionally, inline analysis reduced the time between batches, increased product yield and eliminated the contamination risks inherent in sampling.
Comprehensive portfolio: From micro-bioreactors to cGMP to single use
Endress+Hauser offers a comprehensive Raman measurement portfolio in upstream bioprocessing with proven model transfer and scalability. The ability to transfer a model across scales is critical to a successful tech transfer. Our suite of inline probes enables the work that was done in the laboratory to transfer with the process.
A recent study showing model transfer directly from micro-scale to a large tank stirred bioreactor shows that the large DoE space generated at the micro-scale can be harnessed to efficiently transfer that process knowledge to development.
Rxn-46 or Rxn-10 with Raman optic system for single use
Laboratory and cGMP manufacturing
Laboratory to process development
Scale-up to cGMP manufacturing
Increase production efficiency and product safety with online measurement
The industry examples described throughout this post and in the review papers, paint a compelling picture with convincing metrics to support the ROI of using Endress+Hauser’s in situ Raman spectroscopy in upstream bioprocessing. The results, which include improved yields, faster process development time and lab-to-process scalability, generate a rapid ROI and increase productivity in bioprocessing, along with decreasing operational costs and risks.
Our technology, automation and application experts are ready to partner with you at every stage! We are confident that we can help you achieve your application and business goals. From instrument selection, responsive service, installation and operation support, application support and compliance services, Endress+Hauser provides ongoing comprehensive support to ensure your success.