Particle Analyzer for Subvisible Protein Aggregate Characterization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for monitoring protein aggregates in therapeutic protein products are inadequate, as they cannot characterize subvisible particles in terms of nature, composition, structural properties, chemical properties, amount, and size, which is crucial for ensuring product quality and mitigating immunogenicity risks.
Innovation Solution
The use of a fluorescent dye that distinguishes proteinaceous from non-proteinaceous subvisible particles, allowing for simultaneous detection, counting, and characterization of these particles using a particle analyzer, which includes calibrating the analyzer with a size standard and collecting data from light scatter and fluorescence parameters to determine particle size, number, and presence of proteinaceous material.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional particle monitoring methods are used, then particle detection is possible, but characterization of subvisible particles in terms of nature, composition, structural properties, chemical properties, amount, and size cannot be achieved
Solution Approach 1:
The patent combines multiple characterization capabilities (light scattering for size, fluorescence for composition and nature identification) into a single particle analyzer system, enabling comprehensive subvisible particle characterization without requiring multiple separate analytical instruments
Solution Approach 2:
The particle analyzer is designed to perform multiple functions simultaneously: detecting particle size via light scattering, identifying proteinaceous vs. non-proteinaceous material via fluorescence, and quantifying particle amount, making it a universal tool for comprehensive particle characterization
2Reliability
If subvisible particles are not characterized, then product release is simplified, but immunogenicity risks cannot be mitigated and clinical performance cannot be ensured
Solution Approach 1:
The patent enables preliminary characterization of subvisible particles including identification of proteinaceous aggregates and quantification of particle burden before product release, allowing quality assurance to be established in advance rather than requiring extensive post-release monitoring
Solution Approach 2:
The patent replaces extensive manual quality control procedures and multiple separate analytical tests with an automated particle analyzer that performs comprehensive characterization in a single integrated system, improving both reliability and productivity
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 accurate characterization of subvisible particles, providing essential quality control data to mitigate immunogenicity risks and ensure the clinical performance of therapeutic protein products.
Implementation Method 1
the at least one fluorescent dye includes a first fluorescent dye that stains a proteinaceaous material in a manner that distinguishes the proteinaceaous material from a non-proteinaceaous material
Implementation Method 2
collecting data from at least one light scatter parameter and at least one fluorescence parameter, wherein the data collected from the at least one light scatter parameter represents a particle size based upon the size standard calibration
Data Source
AI summary
The present specification discloses methods of characterizing a population of particles using a particle analyzer. Particles may be characterized by size, absolute number, whether the particle is non-proteinaceous or proteinaceous, whether a proteinaceous particle has or lacks a certain physical property, or any combination thereof.