While currently most production processes for biopharmaceuticals are assessed by laboriuos and time-consuming off-line analytics, a new process enables the monitoring of such processes in real-time. Sensors combined with mathematical models deliver information on the quality and quantity of the product, as well as on content and profile impurities. This allows an instant monitoring of processes, making processes safer, faster, cheaper and more efficient. The share of marketed drugs that have been biotechnologically produced has nearly doubled in the last decade. These biopharmaceuticals include drugs for the treatment of diabetes or rheumatoid arthritis as well as vaccines and cancer therapeutics, making it possible to treat diseases considered incurable just a few years ago.
Quality takes time. But why?
Compared to the chemical synthesis of medical agents, biotechnological processes in living cells are much more flexible and are conducted under more gentle conditions. Although working with bacteria or animal cells is quite challenging due to their structure and complexity of related impurities. Regulatory requirements for product purity require multi-stage purification processes and a high degree of process understanding. Currently, quality is being reviewed and documented through continuous sampling throughout the processes and subsequent analysis. Results are obtained days after completion of individual process steps. These analysis methods only allow a determination of the quality, but no active impact on it.
Time for real-time!
A new system enables the in-process control of the complex purification processes of biopharmaceuticals in real-time. While previous methods often only provide information about one quality characteristic of the product in the ongoing process, the developed method offers information about the product quality and quantity as well as about present impurities in a few seconds. Also, continuous production and quality control of manufacturing processes in real-time have been shown to improve product quality and production efficiency. Already becoming state of the art e.g. in the automotive or food industry, the new process represents a completely new application in biotechnological production.
So how does this process work? A combination of different sensors and mathematical models allow the measurement of correlations between signals and important quality criteria and the monitoring of the system. A user interface enables the visual presentation of the collected data as well as feedback of the system control information. The system already was put into operation and patented in Europe and the US.
Advantage in future innovation
With the new system, the quality can be controlled in real-time via knowledge-based process management. This reduces the risk of batch failure, the overall process duration and the extent of the necessary analyzes. The processes gets safer, faster and more efficient, since product bottlenecks get eliminated. The manufacturing costs can be reduced and resources saved, which in turn contributes to a cost reduction of these high-priced drugs. The use of in-process quality control in real-time makes new standards in the continuous production of biopharmaceuticals possible, giving companies a clear innovation advantage in the future.
This work is based on:
Sauer DG, Melcher M, Mosor M, Walch N, Berkemeyer M, Scharl-Hirsch T, Leisch F, Jungbauer A, Dürauer A: Real-time monitoring and model-based prediction of purity and quantity during a chromatographic capture of fibroblast growth factor 2. 2019, Biotechnol Bioeng, DOI 10.1002/bit.26984
Walch N, Scharl T, Felfödi E, Sauer DG, Melcher M, Leisch F, Dürauer A, Jungbauer A: Prediction of the quantity and purity of an antibody capture process in real-time. 2019, Biotechnol J, DOI 10.1002/biot.201800521
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