A versatile noninvasive method for adsorber quantification in batch and column chromatography based on the ionic...

Area of Science:

• Biopharmaceutical Process Development
• Chromatography
• Chemical Engineering

Background:

• Quality by Design (QbD) and high-throughput process development (HTPD) are vital for biopharmaceutical chromatography.
• Consistent quantification of adsorber amount and column characteristics (e.g., ionic capacity) is essential for comparing data across scales and implementing mechanistic modeling.
• Classical methods like acid-base titration have limitations, especially for robotic batch experiments.

Purpose of the Study:

• To develop a noninvasive method for determining ionic capacity in both column and batch chromatography.
• To enable consistent data comparison across different scales and formats in biopharmaceutical chromatography.
• To improve the reliability of mechanistic modeling by accurately determining column characteristics.

Main Methods:

• Developed a method based on the adsorption/desorption of histidine, a natural, UV-detectable amino acid.
• Applied the method to both column and batch chromatography systems.
• Validated results against classical acid-base titration for column chromatography.
• Adapted the method for robotic batch chromatographic experiments and converted batch adsorber volumes to equivalent compressed column volumes.

Main Results:

• The histidine-based method yielded results comparable to acid-base titration in column chromatography.
• The method is adaptable to robotic batch chromatography, overcoming limitations of traditional techniques.
• Conversion of batch adsorber volumes to equivalent compressed column volumes was achieved.
• Demonstrated improved quality of SMA parameters fitted to batch adsorption isotherms and enhanced prediction of column breakthrough experiments in a case study.

Conclusions:

• The developed histidine-based method provides a reliable and consistent way to determine ionic capacity in chromatography.
• This method supports the Quality by Design framework by enabling accurate data comparison and enhancing mechanistic modeling for biopharmaceutical process development.
• The technique improves the predictive capability of chromatography models, leading to more robust process development.