Continuous Chromatography System for Biopharmaceutical Purification
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Solution Overview
Problem
The biopharmaceutical industry has been slow to adopt continuous processing technologies, which are more efficient and cost-effective, due to the need for large-scale equipment and the limitations of disposable downstream processing capabilities, particularly for high-titer bioreactors producing significant amounts of protein.
Innovation Solution
The development of a novel continuous processing technology (CPT) that utilizes multi-valve arrays and integrated valve cassettes for continuous chromatography, enabling a fully disposable flowpath and reducing the scale of equipment needed, allowing for continuous purification of biopharmaceuticals from bioreactors to final product.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If continuous processing technology is adopted, then productivity and efficiency are improved, but equipment scale and capital investment increase
Solution Approach 1:
The continuous processing system is divided into multiple independent chromatography columns (typically 4-8 columns) that operate in parallel stages. Each column can be independently controlled and processed, allowing the system to handle large volumes through parallel operation rather than requiring a single large-scale continuous processor. This segmentation enables modular scaling where capacity is increased by adding more columns rather than enlarging individual equipment.
Solution Approach 2:
The system transitions from traditional batch processing (single dimension of time) to continuous multi-stage processing (adding the dimension of parallel spatial operation). Multiple columns operate simultaneously at different stages of the purification cycle, creating a multi-dimensional processing architecture that increases throughput without proportionally increasing the volume of any single piece of equipment.
2Ease of operation
If disposable downstream processing components are used, then ease of operation and cleaning time are improved, but device complexity increases
Solution Approach 1:
The system employs disposable chromatography columns and single-use chromatography media that are discarded after a single use or limited number of cycles. This eliminates the need for complex cleaning and sterilization procedures associated with reusable components, significantly reducing downtime and operational complexity. The disposable nature allows rapid replacement without validation or cleaning protocols.
Solution Approach 2:
The system is designed to discard used disposable components and recover the purified product continuously. The disposable columns are discarded after use while the valuable biopharmaceutical product is recovered and moved to the next processing stage. This approach trades the cost of disposable components for reduced cleaning time and simplified operation.
3Manufacturing precision
If multi-valve arrays and integrated valve cassettes are implemented, then manufacturing precision and process control are improved, but device complexity increases
Solution Approach 1:
Multiple valve functions are merged into integrated valve cassettes or manifolds that control flow distribution across multiple chromatography columns. Instead of separate valve assemblies for each column, a single integrated valve system manages all fluid routing, reducing the number of discrete components and simplifying control architecture while maintaining precise flow control.
Solution Approach 2:
The integrated valve cassettes are designed with multi-functionality, serving as flow distributors, collectors, and control elements for multiple columns simultaneously. A single valve cassette can control inlet and outlet flows to several columns, providing universal control functionality that reduces overall system complexity despite the sophisticated control required.
4Loss of time
If continuous chromatography is used, then loss of time is reduced, but quantity of substance (chromatography media) required increases
Solution Approach 1:
The system maintains continuous useful action by operating multiple chromatography columns in parallel stages simultaneously. While one column is in the loading phase, another is in elution, and a third is being regenerated. This continuous overlapping operation eliminates idle time between batch cycles and maintains constant product throughput, reducing total processing time without requiring excessive media volume in any single column.
Solution Approach 2:
The system performs preliminary actions in advance by pre-conditioning and pre-equilibrating chromatography columns before they are needed in the processing sequence. Columns are prepared ahead of time with appropriate buffers and conditions, allowing immediate uptake when product flow reaches them. This eliminates setup time during continuous operation and maintains efficient processing without requiring oversized columns.
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 significantly reduces equipment scale, downtime, and capital investment, enabling faster and more efficient production of biopharmaceuticals, allowing for ton-scale output with reduced costs and increased flexibility in manufacturing processes.
Implementation Method 1
continuous counter-current multi-column simulated moving bed (SMB) chromatography
Implementation Method 2
chromatography media
Implementation Method 3
concentrate the solution to a desired concentration
Data Source
AI summary
The present invention is directed to the development of continuous processing technology for the purification of biopharmaceuticals and biological products, such as monoclonal antibodies, protein therapeutics, and vaccines. Methods for continuous processing of a biological product in a feed stream toward formulation of a purified bulk product are described.