Mass spectrometry (MS) applications in the pharmaceutical industry have long been recognized. It is a highly versatile method and is frequently used for identifying products, reagents, contaminants, and impurities from samples in the research and development of drugs, as well as scale-up and high-volume manufacturing lines.
However, MS instruments are typically large, consume a lot of power, and are expensive equipment that MS specialists must operate in centralized laboratories.
The novel requirements of bioprocessing, used to produce biologics, means that there is a demand for analytical instruments, including mass spectrometers, to deliver real-time information (both online and at-line) at the point of need.
MS provides information-rich data to overcome the increased complexities of bioprocessing.
This article discusses how the deployable and compact mass spectrometer from Microsaic Systems can be employed to sample the media from a bioreactor in real-time to provide critical process monitoring and crucial product quality attributes.
This information can be subsequently used to maximize biologic yields by optimizing the cell media, feeding, and harvesting strategies of the target biologic being produced.
MS point-of-need analysis offers well-timed safety assurance because any harmful PTMs of the product and other dangerous host cell proteins may be controlled and minimized upstream.
Figure 1. Prototype mass spectrometer based on the Microsaic 4000 MiD ® and MiDas sampling. Image Credit: Microsaic Systems plc
Experimental
The study described in this article utilized a prototype system based on the Microsaic 4000 MiD® mass spectrometer and MiDas sampling interface unit, displayed in Figure 1. With an adjustable mass range between 50 and 3200 m/z, the MS can accurately identify proteins and small molecules.
Figure 2. Experimental setup showing the various steps and functions of the MiDas and MiD to analyze cell media and proteins. Image Credit: Microsaic Systems plc
The prototype interface unit enables biological liquids from bioreactors to be sampled, prepared, and separated into an easily ionized electrospray and mass spectrometer-compatible mobile phase.
Figure 2 displays the experimental setup, with representative workflows of both biologic CQAs and cell media monitoring displayed in Figure 3 and Figure 4.
Figure 3. Work-flow of biologic products monitoring in upstream bioprocessing. Image Credit: Microsaic Systems plc
Figure 4. Work-flow of cell media monitoring in upstream bioprocessing. Image Credit: Microsaic Systems plc
Results
Representative proteins were sampled and tested using the same cell media testing setup. Figure 5 presents the mass spectra of various proteins where important CQAs are easy to obtain using a real-time analysis tool. Figure 5 includes an example of this: the automatic protein mass finder.
Figure 5. At-line biologic product CQA monitoring in upstream bioprocessing (a) Ovalbumin (b) Insulin and (c) GFP his-tagged. Image Credit: Microsaic Systems plc
This tool transforms the information-rich data delivered by the MS into an easy-to-understand data set consisting of the most prominent protein mass and a 'Quality Index' for each mass. This index provides a measure of certainty of the protein mass and the input data quality.
This data reduction enables the data from the MS to be easily understood and the operation of the MS close to the point of need by a non-expert.
A representative sample of cell media was sampled and analyzed. Figure 6 presents a typical mass spectrum that identifies five components of the media mix. This chemical information can subsequently control the bioprocess by optimizing the media, feeding, and harvesting strategies.
Figure 6. At-line biologic product CQA monitoring in upstream. Image Credit: Microsaic Systems plc
Conclusion
The study described in this article demonstrates that deployable MS has the potential to be employed for real-time point-of-need applications in upstream bioprocessing for the following:
- Cell media makeup optimization
- Cell media monitoring and feeding
- Biologic product CQA monitoring
The product solution from Microsaic Systems delivers biopharma with an effective tool to help the industry to produce lower-cost and safer biologics.
Microsaic welcomes contact from the biopharmaceutical industry and OEM partners to discuss their needs.
This information has been sourced, reviewed and adapted from materials provided by Microsaic Systems plc.
For more information on this source, please visit Microsaic Systems plc.