Continuous Protein Purification Using Multi-Column Chromatography
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Solution Overview
Problem
Current biomanufacturing processes for therapeutic proteins are not flexible and cost-effective, lacking integrated and continuous systems for efficient production, purification, and polishing of recombinant proteins.
Innovation Solution
The implementation of integrated, continuous processes using two multi-column chromatography systems, including a first periodic counter current chromatography system (PCCS1) for capturing and optionally inactivating recombinant therapeutic proteins, and a second PCCS2 for purifying and polishing using different resins, allowing for continuous production from liquid culture medium to therapeutic protein drug substance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional batch processing methods are used for therapeutic protein production, then process simplicity is maintained, but productivity and manufacturing efficiency are limited
Solution Approach 1:
The patent implements continuous processing where culture medium flows continuously from the bioreactor through multiple chromatography systems (capture, purification, polishing) without batch interruptions. This eliminates downtime between batches and maintains continuous productive action throughout the entire manufacturing line, significantly increasing therapeutic protein production efficiency.
Solution Approach 2:
The patent merges multiple separate processing functions (capture chromatography, purification chromatography, and polishing chromatography) into an integrated continuous system where culture medium passes sequentially through all stages. This consolidation of functions into a unified continuous flow system resolves the contradiction by achieving high productivity through integration while managing complexity through systematic design.
2Manufacturing precision
If multiple chromatography systems are integrated for continuous production, then purification quality is improved, but device complexity increases
Solution Approach 1:
The patent segments the purification process into three distinct continuous chromatography stages: capture (removing bulk impurities), purification (removing remaining impurities), and polishing (achieving final purity). Each segment uses specialized chromatography media optimized for its specific function, allowing high manufacturing precision through targeted purification at each stage while managing overall system complexity through functional segmentation.
Solution Approach 2:
The patent applies local quality by using different chromatography media with specific properties at different stages of the process. The capture stage uses media optimized for high-binding capacity, purification uses media for selective impurity removal, and polishing uses media for final purity enhancement. This localized optimization of media properties at each stage achieves superior overall purification quality.
3Productivity
If continuous processing is implemented, then productivity increases, but process control difficulty increases
Solution Approach 1:
The patent implements feedback control by monitoring critical parameters (flow rates, pressure differentials, UV absorbance) throughout the continuous processing system and adjusting operations accordingly. This feedback mechanism maintains process stability and quality consistency despite the increased complexity of continuous operation, resolving the contradiction between high productivity and ease of control.
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
This approach enables flexible and cost-effective continuous production of therapeutic proteins by efficiently capturing, purifying, and polishing recombinant proteins, reducing impurities and maintaining high purity throughout the process.
Implementation Method 1
capturing the recombinant therapeutic protein in the liquid culture medium using the PCCS 1, where the eluate of the PCCS 1 containing the recombinant therapeutic protein is continuously fed into a second periodic counter current chromatography system (PCCS2) and performing at least two different unit operations of purifying and polishing the recombinant therapeutic protein using the PCCS2
Data Source
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AI summary
Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.