Shear Stress Application for Protein Stability Analysis

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Solution Overview

Problem

Existing methods for simulating shear stress on particles in solutions, such as proteins, during filling processes are inadequate as they often damage the particles and fail to provide systematic, reproducible data on shear stress and stability, leading to product instability and quality issues.

Innovation Solution

A device comprising two all-glass syringes connected by a cannula with Luer-Lock connectors, an integrated optical measuring system, and a mechanical drive for controlled movement, allowing for the application of defined shear rates and durations, enabling the quantification of protein stability and aggregation through PCS or turbidity measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional filling processes are used to determine shear stress impact, then product stability data can be obtained, but the processes are not systematic and reproducible, leading to inadequate data quality

Engineering Contradiction:
Improveshear stress measurement precisionVSAvoiddata reproducibility
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention applies parameter changes by systematically varying shear rate and shear duration as independent variables to establish their individual impacts on protein stability. This controlled parameter variation enables reproducible data collection and allows for the development of predictive models for shear stress effects in filling processes.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a universal testing framework that can evaluate different protein formulations, filling processes, and storage conditions using standardized shear stress application protocols. This multi-functional approach enables systematic comparison across different products and processes, improving both measurement precision and data reliability.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If high shear rates are applied to simulate filling processes, then process proximity is improved, but particle damage and aggregation increase

Engineering Contradiction:
Improveprocess simulation accuracyVSAvoidparticle damage
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The invention applies partial action by using defined, controlled shear rates and durations that simulate filling processes without exceeding the threshold that causes excessive particle damage. This allows for process simulation while maintaining particle stability through optimized parameter selection.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The invention implements dynamics by allowing flexible adjustment of shear rate and shear duration parameters to match different filling process conditions. This dynamic parameter control enables accurate process simulation while adapting to the specific stability characteristics of different protein formulations.

Inventive Principle:
Principle #15Dynamics

3Measurement precision

If extensive sampling is performed to assess protein stability, then measurement accuracy improves, but sample consumption increases

Engineering Contradiction:
Improvestability assessment accuracyVSAvoidsample consumption
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The invention applies preliminary action by performing stability assessments under defined shear stress conditions before actual filling processes. This preliminary testing allows for formulation optimization and process parameter selection using minimal samples, preventing the need for extensive sampling during later stages.

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

The device allows for reproducible simulation of shear stress conditions, enabling the comparison of protein stability across different formulations and the evaluation of filter effects, while minimizing sample usage and maintaining process proximity with inert materials, thus ensuring accurate assessment of protein stability and formulation optimization.

Implementation Method 1

Each of these processes inevitably involves fluidic flows in which shear rates occur. These shear rates represent a mechanical shear stress for the particles dispersed in the solution

Methodology Applied
Scientific EffectShear stress: Shear Stress

Implementation Method 2

The effects of shear stress on macromolecules (e.g., protein aggregation) are analytically quantified, for example, by PCS (protein aggregation) or turbidity measurements

Methodology Applied
Scientific EffectTurbidity measurement: Absorption Spectroscopy

Data Source

PatentEP1975597B1Shearing stress application
Publication Date: 2020.07.15 BOEHRINGER INGELHEIM PHARMA GMBH & CO KG
  • EP1975597B1 patent drawingFigure 1A~1B
  • EP1975597B1 patent drawingFigure 2~3
  • EP1975597B1 patent drawingFigure 4~5

AI summary

The present invention relates to an apparatus for determining the shear sensitivity of particles in solutions and methods for determining the respective shear rates or shear stress.