Parallel Chromatography Skids for Continuous Biomanufacturing

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Traditional chromatography systems, particularly large-scale single-column systems and complex multi-column setups, face challenges such as increased processing time, high costs, environmental impact, and reduced flexibility due to large facility footprints and complex configurations, while also suffering from poor fault tolerance and inefficient use of resources.

Innovation Solution

A continuous parallel chromatography system comprising multiple independent chromatography column skids operating in parallel, with each skid capable of independent batch processing, and a control circuit that synchronizes operations to manage full cycles including long and short steps, allowing for flexible and expandable processing without complex interconnections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Area of stationary object

If a single large scale chromatography column is used, then the facility footprint is reduced, but the processing time increases and flexibility decreases

Engineering Contradiction:
Improvefacility footprintVSAvoidprocessing time
Core Design Contradiction:
Area of stationary objectVSLoss of time

Solution Approach 1:

The system divides the chromatography operation into multiple independent columns (first column and second column) that can operate simultaneously in parallel. This segmentation allows the processing to be distributed across multiple units, reducing the time required compared to a single large column while maintaining a compact facility footprint through modular arrangement.

Inventive Principle:
Principle #1Segmentation

2Productivity

If complex multi-column cycling strategies are used, then resin utilization improves, but the device complexity increases

Engineering Contradiction:
Improveresin utilizationVSAvoiddevice complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system uses multiple independent chromatography columns that can be operated in parallel with simplified cycling strategies. Each column operates independently with standard load-wash-elute-regen cycles, eliminating the need for complex valve configurations and sophisticated control strategies required by traditional multi-column systems, thereby reducing device complexity while maintaining high resin utilization.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system employs periodic cycling of columns through standardized operations (load, wash, elute, regenerate) in a coordinated manner. Columns are cycled periodically and independently, allowing continuous processing without requiring complex real-time control strategies, thus achieving high productivity with simpler device architecture.

Inventive Principle:
Principle #19Periodic action

3Productivity

If columns are interconnected in series, then continuous output is achieved, but fault tolerance decreases

Engineering Contradiction:
Improvecontinuous outputVSAvoidfault tolerance
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system uses multiple independent chromatography columns that are not interconnected in series but operate in parallel. Each column is a独立的 processing unit with its own fluid path and control, allowing one column to be isolated and serviced without affecting the operation of other columns. This segmentation provides inherent fault tolerance while maintaining continuous output capability through parallel operation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system allows individual columns to be taken offline for regeneration or maintenance while other columns continue to process. A column that has completed its cycle can be isolated, regenerated, and brought back into service, while the continuous output is maintained by other active columns. This enables fault tolerance and continuous operation without requiring complex interconnections.

Inventive Principle:
Principle #34Discarding and recovering

4Productivity

If multiple columns are connected with complex valving systems, then process continuity is improved, but ease of operation decreases

Engineering Contradiction:
Improveprocess continuityVSAvoidease of operation
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The system divides the process into multiple independent column units, each with standardized operations and simple fluid paths. This segmentation eliminates the need for complex valving systems and interconnections between columns, making each unit easy to operate independently while achieving process continuity through parallel operation and coordinated cycling of multiple simple units.

Inventive Principle:
Principle #1Segmentation

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 reduces processing time, minimizes equipment costs, enhances fault tolerance, and promotes efficient use of resources, enabling flexible and efficient biomanufacturing with reduced environmental impact by allowing individual skid isolation and continuous operation without halting the entire process.

Implementation Method 1

a first chromatography column of a plurality of chromatography columns is received with feedstock containing a protein and impurities

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

a first pump of a plurality of pumps is used to load a first amount of the feedstock onto the first chromatography column

Methodology Applied
Scientific EffectPumping: Pump

Implementation Method 3

a first ultraviolet (UV) monitor of a plurality of UV monitors is used to monitor an eluate stream from the first chromatography column

Methodology Applied
Scientific EffectUV absorption: Absorption Spectroscopy

Data Source

PatentUS20240075406A1Parallel chromatography systems and methods
Publication Date: 2024.03.07 AMGEN INC
  • US20240075406A1 patent drawing
  • US20240075406A1 patent drawing
  • US20240075406A1 patent drawing

AI summary

Parallel chromatography systems and continuous manufacturing methods are described herein that utilize two or more chromatography column skids having columns operating in parallel with automation controls governing which column to load at a given time.