Chromatography technique developed as continuous on-line PAT tool

Researchers have demonstrated the feasibility of on-line mass spectrometry (MS) measurement using an on-line micro simulated moving bed chromatography (µSMB)- mass spectrometry system. It provides a versatile process analytical technology (PAT) tool by combining the detection power of mass spectrometry for various product attributes with the advantages of continuous on-line analytics.

In the proof-of-concept study, integrating the µSMB significantly increased mass spectrometry sensitivity, by removing over 98 percent of the buffer substances, a paper published in Analytical and Bioanalytical Chemistry explained.

Analytical methods for PAT applications in biopharma

Authors of the paper wrote that overall, many established off-line analytical methods such as mass spectrometry, are not often considered for PAT applications in biopharmaceutical processes. They are “limited to at-line analysis due to the sample preparation and the associated complexity required”.

Therefore, with the growing importance of continuous manufacturing in pharma, there is a need for powerful continuous analytical tools, Diehm et al. emphasised. The authors highlighted that a critical challenge for the next generation of biomanufacturing is “the limited number of process observations combined with long analysis times for biomolecules”.

With mass spectrometry’s powerful capability in detecting a wide range of quality attributes, “its application as a PAT tool is promising”, the paper stated.

The paper noted that while continuous implementations of chromatography processes exist at a preparative scale, they have so far, not been applied for analytical purposes. This is due to the equipment not being designed to handle small volumes.

Overcoming limitations in continuous analytical tools

To overcome this, Diehm et al. developed a widely used continuous chromatography technique to the micro-scale.

A continuous buffer exchange of a protein solution based on size-exclusion chromatography (SEC) with the µSMB system was performed in the study. Successful hyphenation of a µSMB to an ESI-MS system was achieved, demonstrating that the µSMB is a valuable tool for on-line sample pre-processing.

Future applications of the µSMB system

An advantage of the µSMB, according to the paper, is use of the countercurrent principle, which was shown to lead to a high separation efficiency, even with poor performance of the single chromatography columns. Positively, the paper stated that the µSMB system can be adapted to any type of multi-column chromatography and used to hyphenate it to mass spectrometry.

The authors concluded that µSMB is a valuable tool for numerous challenging separation problems and “are not limited to process control at a preparative scale, but can also provide useful insights during process development.”

Global PAT market expected to exceed $10b in 2032