Surfactant Wash Buffer for CEX Viral Clearance
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Solution Overview
Problem
Current protein purification processes, particularly for monoclonal antibodies, require multiple chromatography steps which reduce protein yield, increase costs, and complicate manufacturing due to limited viral clearance capabilities of cation exchange chromatography (CEX) as a standalone polishing step.
Innovation Solution
Incorporating a surfactant into the wash buffer during CEX chromatography enhances viral clearance, allowing for the removal of additional polishing steps like anion exchange chromatography, thereby simplifying the process and improving target product recovery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple chromatography steps (ProA, CEX, AEX) are used for protein purification, then viral clearance and impurity removal are improved, but protein yield decreases and manufacturing complexity increases
Solution Approach 1:
The patent combines viral clearance function into the CEX chromatography step by using a surfactant-containing wash buffer, merging the previously separate functions of CEX (impurity removal) and AEX (viral clearance) into a single step, thereby reducing the number of chromatography steps while maintaining both impurity removal and viral clearance capabilities
Solution Approach 2:
The CEX chromatography step is enhanced to perform multiple functions simultaneously: removing host cell proteins, DNA, aggregates, and clearing viruses, making it a multi-functional step that replaces what were previously separate polishing steps
2Reliability
If multiple chromatography steps are used for protein purification, then viral clearance and impurity removal are improved, but manufacturing complexity increases
Solution Approach 1:
The patent merges multiple chromatography steps into a single CEX step by adding surfactant to the wash buffer, combining viral clearance and impurity removal functions into one operation, thereby reducing manufacturing complexity while maintaining reliability
Solution Approach 2:
The enhanced CEX step serves as a universal polishing step that performs multiple functions (HCP removal, DNA removal, aggregate removal, and viral clearance) that were previously distributed across multiple separate steps, simplifying the overall manufacturing process
3Device complexity
If CEX is used as the only polishing step, then manufacturing complexity is reduced, but viral clearance capability is insufficient
Solution Approach 1:
The patent changes the chemical composition parameter of the CEX wash buffer by adding surfactant, which fundamentally alters the viral clearance capability of the CEX step, enabling it to achieve adequate viral clearance while maintaining simplicity
Solution Approach 2:
Surfactant acts as an intermediary substance in the CEX wash buffer that mediates the interaction between the chromatography support and viruses, enhancing viral clearance capability without requiring additional chromatography steps
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 surfactant-enhanced CEX process achieves effective viral clearance without compromising impurity removal, enabling the reduction of chromatography steps and manufacturing complexity, and maintaining protein yield.
Implementation Method 1
The application of the wash procedure, and its associated robust viral clearance capability, can enable the removal of certain other polishing chromatography steps, such as AEX, resulting in reduced number of chromatography steps needed.
Implementation Method 2
Cation exchange (CEX) for DNA, HCP and aggregate removal
Implementation Method 3
Protein A (ProA) for product recovery and host cell protein (HCP) removal
Data Source
AI summary
A wash buffer comprising a surfactant for use in affinity and cation exchange chromatography to purify proteins of interest from protein aggregates and to remove and/or inactivate viruses. When used during affinity or cation exchange chromatography for the purification of a protein of interest, such as an antibody, the wash buffer significantly improves viral clearance from the preparation, while also reducing the levels of host cell proteins and protein aggregates. Following affinity or cation exchange chromatography with the wash buffer, the protein of interest may be further purified using other chromatography and filtration operations.