GM-CSF Liquid Formulation Stabilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current protein pharmaceutical formulations, particularly those containing Granulocyte-macrophage colony stimulating factor (GM-CSF), face challenges with stability at high concentrations and during long-term storage, leading to aggregation and degradation, which affects bioactivity and requires complex manufacturing processes.
Innovation Solution
A stable liquid formulation of GM-CSF is developed using a combination of a non-reducing sugar like sucrose or trehalose and a sugar alcohol such as sorbitol, along with a histidine buffer system, to maintain the protein in a dissolved state and prevent aggregation, allowing for subcutaneous administration and room temperature stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If protein pharmaceuticals are stored in liquid formulation at high concentrations, then ease of manufacture and user convenience are improved, but protein stability deteriorates due to aggregation and degradation
Solution Approach 1:
The patent introduces specific stabilizing agents (such as sugars, sugar alcohols, amino acids, and buffers) as intermediary substances that mediate between the protein and the formulation environment. These intermediaries prevent direct harmful interactions between the protein and formulation components, thereby maintaining protein stability at high concentrations in liquid formulation without compromising ease of manufacture.
Solution Approach 2:
The patent systematically adjusts formulation parameters including pH, ionic strength, temperature, and concentration levels to optimize protein stability. By changing these parameters within specific ranges, the formulation maintains protein stability while preserving the advantages of liquid formulation for manufacturing and user convenience.
2Stability of the object's composition
If protein pharmaceuticals undergo lyophilization to improve stability, then protein stability is improved, but user convenience deteriorates due to complex reconstitution requirements
Solution Approach 1:
The patent extracts the stabilization function from the lyophilization process by incorporating stabilizing agents directly into the liquid formulation. This allows the formulation to achieve protein stability without requiring lyophilization, thereby eliminating the need for reconstitution and improving user convenience while maintaining stability.
3Stability of the object's composition
If formulation components are optimized to maximize protein stability, then protein stability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent segments the formulation into functional components: stabilizing agents, buffers, and excipients, each serving specific purposes. This segmentation allows for systematic optimization of stability while maintaining manufacturing simplicity, as each component can be added and controlled independently without requiring complex interactions between all formulation elements.
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 formulation achieves high concentration stability of GM-CSF, minimizing aggregation and maintaining bioactivity over long-term storage and freeze/thaw cycles, reducing manufacturing complexity and side effects associated with high viscosity.
Implementation Method 1
A stable liquid formulation of GM-CSF is developed using a combination of a non-reducing sugar like sucrose or trehalose and a sugar alcohol such as sorbitol, along with a histidine buffer system, to maintain the protein in a dissolved state and prevent aggregation
Data Source
AI summary
The present invention relates to aqueous formulations comprising a compound neutralizing GM-CSF in concentrations of at least about 20 mg/ml, a tonicity modifier and a buffer, wherein the composition is stable. The ingredients of the formulation preferably provide stability to the compound neutralizing GM-CSF in view of long-term storage. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory and autoimmune disorders, preferably including allergic and psoriatic disorders, as well as arthritic and asthmatic disorders. Furthermore, a kit comprising the formulation of the invention is provided.