Partial Batch Chromatography Biomolecule Purification

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Solution Overview

Problem

Current methods for optimizing chromatographic purification processes for biomolecules on an industrial scale are inefficient, requiring extensive trial-and-error approaches and lacking systematic optimization, leading to suboptimal results due to the complexity of varying parameters such as pH, salt content, and buffer usage, which complicates the removal of impurities and contaminants while maintaining biological activity and yield.

Innovation Solution

A partial batch process is employed on a small scale, where the chromatography material is suspended during loading but not during elution, allowing for the optimization of loading, washing, and elution conditions, which are then reproducible on a larger scale, enabling simultaneous variation of multiple parameters to determine optimal chromatography conditions for biomolecule purification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional trial-and-error methods are used to optimize chromatographic purification processes, then comprehensive parameter testing can be performed, but the process requires extensive time and numerous preliminary tests

Engineering Contradiction:
Improvepurification optimizationVSAvoidprocess development time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent creates a simplified copy model using multi-well plates that replicates the essential chromatographic purification process at a reduced scale. This copying approach allows systematic optimization of purification parameters without requiring extensive time and resources for full-scale trials, directly resolving the contradiction between achieving manufacturing precision and reducing time loss.

Inventive Principle:
Principle #26Copying

2Manufacturing precision

If multiple parameters are varied simultaneously in traditional optimization, then comprehensive optimization can be achieved, but the complexity of the process increases significantly

Engineering Contradiction:
Improvechromatography condition optimizationVSAvoidoptimization process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent segments the optimization process by dividing it into distinct phases: first optimizing binding conditions, then elution conditions, and finally polishing conditions. Each phase focuses on specific parameters rather than varying all parameters simultaneously, thereby achieving comprehensive optimization while maintaining manageable process complexity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a new dimension of optimization by implementing a multi-stage sequential approach that adds temporal structure to the parameter optimization process. This dimensional change allows systematic exploration of parameter space without overwhelming complexity, as each stage builds upon the previous optimization results.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Loss of substance

If small-scale screening is used to optimize chromatography conditions, then material usage is minimized, but the results may not be reproducible on larger industrial scale

Engineering Contradiction:
Improvematerial usageVSAvoidscalability of results
Core Design Contradiction:
Loss of substanceVSReliability

Solution Approach 1:

The patent performs preliminary optimization actions on a small scale using multi-well plates to establish optimal conditions before scaling up to industrial production. The segmented optimization approach ensures that conditions are systematically determined in advance, making the results reliably transferable to larger scales while minimizing material consumption during the optimization phase.

Inventive Principle:
Principle #10Preliminary action

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 method allows for the rapid and cost-effective optimization of chromatographic processes, ensuring high purification efficiency and biological activity on an industrial scale, reducing the need for extensive preliminary testing and minimizing material usage.

Implementation Method 1

chromatographic purification processes for biomolecules

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

chromatographic processes for the separation (purification) of biological molecules

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP2032230B1Process for optimizing chromatographic purification processes for biomolecules
Publication Date: 2014.04.02 BOEHRINGER INGELHEIM PHARMA GMBH & CO KG
  • EP2032230B1 patent drawingFigure 1
  • EP2032230B1 patent drawingFigure 2
  • EP2032230B1 patent drawingFigure 3~3.2

AI summary

The invention relates to a process for finding suitable parameters for the chromatographic purification of biomolecules. The process consists of equilibration, loading, washing and elution steps, wherein this sequence of steps is carried out in the partial batch process. The parameters determined in small, preferably a plurality, of parallel batches give information on the chromatography conditions under which a given biomolecule may be optimally purified by column chromatography, if appropriate even on a relatively large scale.