Spectroscopic sensors for in-line bioprocess monitoring in research and pharmaceutical industrial application

Abstract

The use of spectroscopic sensors for bioprocess monitoring is a powerful tool within the process analytical technology (PAT) initiative of the US Food and Drug Administration. Spectroscopic sensors enable the simultaneous real-time bioprocess monitoring of various critical process parameters including biological, chemical, and physical variables during the entire biotechnological production process. This potential can be realized through the combination of spectroscopic measurements (UV/Vis spectroscopy, IR spectroscopy, fluorescence spectroscopy, and Raman spectroscopy) with multivariate data analysis to obtain relevant process information out of an enormous amount of data. This review summarizes the newest results from science and industry after the establishment of the PAT initiative and gives a critical overview of the most common in-line spectroscopic techniques. Examples are provided of the wide range of possible applications in upstream processing and downstream processing of spectroscopic sensors for real-time monitoring to optimize productivity and ensure product quality in the pharmaceutical industry.

Analytical evaluation of sensor measurements

“…The measurement of real samples is of interest. Recently, applications in various fields have been reviewed: sensors in in-line sensor monitoring in bioprocesses [30]; the concept of and first results for nanosensors for neurotransmitters [31]; and a noninvasive method for cancer diagnostics by detection of volatile organic compounds in exhaled breath, demonstrating the future prospects of sensors [32]. Recently, sensors have proven their capabilities even in effect-directed analysis [33] and imaging [34].…”

Inline noninvasive Raman monitoring and feedback control of glucose concentration during ethanol fermentation

“…Therefore, there is a growing need in the fermentation process to find suitable sensors to monitor and control critical process parameters in real‐time. Over the last years, many techniques have been studied and developed for real‐time bioprocess monitoring by using spectroscopic methods, such as UV–visible, mid‐ and near‐infrared (MIR/NIR), fluorescence, and Raman spectroscopy . Among these spectroscopic technologies, Raman spectroscopy is a challenging, but a very promising technique for applications in bioprocess monitoring.…”

Process‐wide control and automation of an integrated continuous manufacturing platform for antibodies

“…Extensive reviews, summarizing already existing process analytical technologies are available (Glassey et al, 2011; Holzberg et al, 2018; Rathore & Kapoor, 2015; Read et al, 2010a, 2010b; Simon et al, 2015). Especially, the use of spectroscopic tools seems powerful to extract process‐relevant online information (Buckley & Ryder, 2017; Claßen, Aupert, Reardon, Solle, & Scheper, 2017; Rowland‐Jones, van den Berg, Racher, Martin, & Jaques, 2017; Rüdt, Briskot, & Hubbuch, 2017). Alternatively, atline analytical devices, such as HPLC systems, can give important process insight along the sequence of unit operations in the manufacturing platform (Karst et al, 2017).…”