Micro simulated moving bed chromatography-mass spectrometry as a continuous on-line process analytical tool

Area of Science:

• Biopharmaceutical Manufacturing
• Analytical Chemistry
• Process Analytical Technology (PAT)

Background:

• Continuous manufacturing offers efficiency gains in the biopharmaceutical industry.
• Existing analytical methods like mass spectrometry (MS) are often limited to at-line analysis due to complex sample preparation.
• There is a need for robust continuous analytical tools for real-time process monitoring.

Purpose of the Study:

• To investigate the use of a micro simulated moving bed chromatography (µSMB) system for continuous on-line sample preparation for MS.
• To demonstrate the feasibility of integrating µSMB with MS for biopharmaceutical process analytical technology (PAT).
• To assess the effectiveness of µSMB in removing interfering buffer substances for improved MS sensitivity.

Main Methods:

• Utilized a newly developed micro simulated moving bed chromatography (µSMB) system.
• Performed continuous on-line sample preparation for mass spectrometry (MS).
• Demonstrated buffer exchange from Tris to ammonium acetate for a myoglobin protein solution to facilitate ESI-MS measurements.

Main Results:

• Successfully integrated µSMB for continuous on-line sample preparation for MS.
• Achieved over 98% removal of interfering buffer substances (Tris), significantly increasing MS sensitivity.
• Demonstrated the continuous on-line MS measurement of a protein solution.

Conclusions:

• The integration of µSMB with MS is feasible for continuous on-line analysis in biopharmaceutical manufacturing.
• µSMB-MS serves as a versatile PAT tool, combining MS detection capabilities with continuous on-line analytics.
• This approach enhances MS sensitivity and enables real-time monitoring of product attributes.