Multi-Zone HIC for Continuous Polypeptide Preparation
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Solution Overview
Problem
Chromatography processes for preparing polypeptides, such as hydrophobic interaction chromatography (HIC), are inefficient due to long run times, high buffer and separation medium usage, and non-automated steps, which increase costs and reduce efficiency in drug product preparation.
Innovation Solution
A method involving a HIC apparatus with multiple zones and columns, where the residence time for the target polypeptide and mobile phases are synchronized, allowing for efficient passage through outlets, and includes regeneration cycles using equilibration, wash, and alkaline solutions to enhance productivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If standard batch HIC steps are used, then polypeptide separation can be achieved, but the time needed to run each stage increases the total processing time and reduces efficiency
Solution Approach 1:
The patent implements continuous chromatography where multiple columns are operated in sequence without interruption. While one column is loading sample, another is eluting, and a third is regenerating, creating a continuous production stream that eliminates idle time between batch cycles and significantly reduces total processing time.
Solution Approach 2:
The system divides the chromatography process into multiple parallel columns, each performing different operations simultaneously. This segmentation allows the loading, elution, and regeneration steps to occur in parallel across different columns, transforming a sequential batch process into a parallel continuous process that reduces total time.
2Productivity
If standard batch HIC steps are used, then polypeptide separation can be achieved, but the amount of buffer and separation medium used increases costs
Solution Approach 1:
The continuous chromatography system recovers and reuses buffer and separation medium by circulating it through multiple columns in sequence. Instead of discarding buffer after a single use in batch mode, the system recovers it during regeneration phases and makes it available for subsequent loading cycles, significantly reducing material consumption.
Solution Approach 2:
The same buffer and separation medium serve multiple functions across different columns and time periods. A single volume of buffer can be used for loading in one column while the same buffer is being eluted from another column and regenerated in a third, making the medium multi-functional and reducing overall consumption.
3Productivity
If non-automated aspects of the process are used, then operational flexibility is maintained, but process efficiency and productivity are reduced
Solution Approach 1:
The continuous chromatography system is designed to operate automatically through programmed control of multiple columns. The system self-regulates the sequencing of loading, elution, and regeneration cycles across columns without requiring manual intervention, enabling unattended operation while maintaining high productivity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method achieves a productivity of at least 50 g/L·hr, reducing idle time and media consumption while maintaining high efficiency in polypeptide preparation.
Implementation Method 1
chromatography, such as hydrophobic interaction chromatography (HIC), affinity chromatography, and the like, may be performed as a part of drug product preparation processes
Data Source
AI summary
Embodiments of the present disclosure are directed to methods for preparing a target polypeptide from a mixture including the target polypeptide. The method may include contacting the mixture to a hydrophobic interaction chromatography (HIC) apparatus including multiple chromatographic zones. The method may further include passing the target polypeptide through the outlets of at least a first zone and a second zone of the HIC apparatus. A residence time for the mixture including the target polypeptide in a first zone may be approximately the same as a residence time of one or more mobile phases in the second zone.