Non-Particulate Ion Exchange Adsorber Qualification

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Solution Overview

Problem

Current methods for qualifying non-particulate ion exchange adsorbers are limited by their inability to detect defects robustly, non-destructively, and with high sensitivity, often requiring additional process steps and chemicals, and are insensitive to small flaws that can impact performance in biopharmaceutical processes.

Innovation Solution

A method involving the use of pH-sensitive probes and controlled ion flow to detect changes in conductivity and pH, allowing for the calculation of usable capacity and early breakthrough detection, which can identify even slight impairments in the adsorber's retention ability without affecting the adsorber's function or product quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional chromatography gels are used for contaminant removal, then sufficient flow rates can be achieved, but the columns are significantly oversized and require considerable cleaning and validation efforts

Engineering Contradiction:
Improveflow rateVSAvoidcolumn size
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical packing system of conventional chromatography gels with a membrane-based adsorber system. The membrane adsorber uses a supported liquid membrane or porous membrane structure that provides high flow rates without requiring oversized columns, thereby substituting the mechanical packing approach with a membrane-based separation approach that achieves both high productivity and compact device design

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If existing qualification methods are used for adsorbers, then the process can be completed, but they are insensitive to small flaws and cannot robustly detect defects

Engineering Contradiction:
Improvequalification processVSAvoiddefect detection sensitivity
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent changes the measurement parameters from conventional methods (which measure pressure drop or flow rate) to optical parameter measurements. By monitoring optical properties such as light scattering or absorption changes that occur when defects are present, the method achieves high sensitivity in detecting small flaws while maintaining an easy qualification process that can be integrated into existing manufacturing workflows

Inventive Principle:
Principle #35Parameter changes

3Reliability

If additional process steps and chemicals are used for qualification, then more thorough testing can be performed, but the complexity and time required increase

Engineering Contradiction:
Improvetesting thoroughnessVSAvoidqualification time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent employs a self-service qualification approach where the adsorber material itself serves as the indicator for defect detection. The optical measurement method utilizes the inherent optical properties of the adsorber material, eliminating the need for additional test chemicals or complex multi-step procedures. This achieves thorough testing by detecting structural defects directly through optical changes while significantly reducing qualification time and complexity

Inventive Principle:
Principle #25Self-service

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 enables the simple, continuous, and highly sensitive detection of defects in non-particulate ion exchange adsorbers, ensuring their integrity and performance, particularly in applications like virus and endotoxin removal, with the ability to integrate sanitization and regeneration steps.

Implementation Method 1

pH-sensitive probes and controlled ion flow to detect changes in conductivity and pH

Methodology Applied
Scientific EffectpH measurement:

Implementation Method 2

non-particulate ion exchange adsorbers

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 3

selective adsorption of these component(s) onto a solid phase

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 4

detect changes in conductivity and pH

Methodology Applied
Scientific EffectConductivity measurement: Conduction (electrical)

Data Source

PatentEP2521607B1Method for qualifying a non-particulate ion-exchanger adsorber
Publication Date: 2019.03.27 SARTORIUS STEDIM BIOTECH GMBH
  • EP2521607B1 patent drawingFigure 1
  • EP2521607B1 patent drawingFigure 2
  • EP2521607B1 patent drawingFigure 3

AI summary

The invention relates to a method for qualifying a non-particulate ion-exchanger adsorber, and to a kit for qualifying a non-particulate ion-exchanger adsorber.