Aflibercept Composition With 20% Truncation Variant Limit
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Solution Overview
Problem
Existing pharmaceutical compositions of aflibercept face challenges in maintaining stability and efficacy due to the presence of truncation variants, which are difficult to remove and affect the binding and biological activities of the protein, complicating the production process and increasing costs.
Innovation Solution
A composition comprising aflibercept with a truncation variant (T100) is developed, where the content of the variant is controlled to be less than or equal to 20%, using peptide mass fingerprinting analysis, allowing for simplified production and maintaining the protein's binding and biological activities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional purification methods are used to remove truncation variants, then the purity of aflibercept is improved, but the production complexity and cost increase
Solution Approach 1:
The patent changes the acceptance criterion parameter from traditional high purity requirements to allowing truncation variant content up to 20%. This parameter change eliminates the need for complex additional purification steps while maintaining product quality, as the truncation variant does not significantly affect binding activity or biological effects when within this threshold.
2Reliability
If additional purification steps are added to remove truncation variants, then the quality control is improved, but the production time and cost increase
Solution Approach 1:
The patent converts the harmful effect of truncation variants into a beneficial acceptance criterion. Instead of viewing truncation variants as contaminants to be eliminated, the patent establishes that variants within 20% do not compromise product efficacy. This converts the previously harmful presence of variants into an acceptable production reality, eliminating time-consuming purification steps while maintaining quality control through alternative assessment methods.
3Reliability
If strict quality control measures are implemented to eliminate all variants, then the product efficacy is improved, but the manufacturing cost increases
Solution Approach 1:
The patent changes the quality control parameter from eliminating all variants to accepting up to 20% truncation variant content. This parameter change maintains product efficacy by establishing that variants within this threshold do not significantly impact binding activity or biological effects, while substantially reducing manufacturing costs by eliminating the need for expensive additional purification steps.
Data Source
AI summary
Provided is a composition comprising aflibercept and a variant thereof, wherein the variant is a truncation variant with a truncated VEGF binding portion of aflibercept, and wherein the content of the truncation variant is less than or equal to about 20% by mass percentage. Also provided is a pharmaceutical formulation comprising the composition. Further, provided are a method for detecting the variant and use of the variant in quality inspection or quality control of an aflibercept-containing product.