Multi-attribute method performance profile for quality control of monoclonal antibody therapeutics

Area of Science:

• Biopharmaceutical analysis
• Analytical chemistry
• Mass spectrometry

Background:

• Multi-attribute methods (MAM) are crucial for biotherapeutic protein characterization.
• Peptide mapping with high-resolution mass spectrometry provides detailed structural and variant information.
• Current methods for product release and stability testing can be time-consuming and require multiple assays.

Purpose of the Study:

• To define the desired performance profile for MAM in monoclonal antibody (mAb) product characterization.
• To address scientific challenges in MAM method validation for biotherapeutics.
• To develop and validate a platform MAM strategy for efficient product development and quality control.

Main Methods:

• Utilized peptide map analysis with high-resolution mass spectrometry for biotherapeutic protein characterization.
• Developed a platform method validation strategy for multiple mAb products with similar properties.
• Applied the Analytical Target Profile concept and regulatory guidelines for method validation design.
• Implemented a comprehensive system suitability control strategy for sample preparation, instrument operation, and data analysis.

Main Results:

• Demonstrated the capability of MAM to provide structural information, quantify variants/degradants, and detect lot-to-lot changes.
• Successfully applied a platform validation strategy to multiple mAb products, minimizing product-specific validation efforts.
• Showcased sufficient method performance for quantitative measurement of product variants and degradants.
• Validated MAM as a robust tool for analytical monitoring from early development to manufacturing QC.

Conclusions:

• A validated MAM workflow using peptide mapping and mass spectrometry is effective for comprehensive biotherapeutic protein characterization.
• The developed platform validation strategy enables efficient and reliable analytical monitoring of mAb products.
• MAM can serve as a single, powerful method for product release and stability testing, replacing multiple traditional assays.