A high-resolution multi-attribute method for product characterization, process characterization, and quality control...

Area of Science:

• Biopharmaceutical manufacturing
• Analytical chemistry
• Quality control

Background:

• Conventional methods for monitoring therapeutic protein Critical Quality Attributes (CQAs) like CEX and rCE-SDS can obscure detection and quantification due to complex peak compositions.
• Existing analytical techniques often require multiple assays to assess various CQAs, increasing complexity and time.

Purpose of the Study:

• To develop and qualify a high-resolution Multi-Attribute Method (MAM) for comprehensive monitoring of therapeutic protein CQAs.
• To replace multiple conventional analytical methods with a single, more sensitive MAM approach.
• To integrate MAM with process characterization and quality control (QC) for enhanced biomanufacturing oversight.

Main Methods:

• Development and qualification of a high-resolution Multi-Attribute Method (MAM).
• Implementation of MAM in process characterization, release assays, and stability studies within quality control (QC).
• Application of Design-of-Experiments (DoE) in conjunction with MAM to define process parameter ranges.

Main Results:

• The qualified MAM effectively monitors multiple CQAs, including oxidation, deamidation, clipping, and glycosylation, with high resolution.
• MAM replaced several conventional methods, offering improved detection and quantification of specific CQAs.
• Integration of MAM and DoE identified optimal multivariate process parameter ranges for consistent CQA levels.

Conclusions:

• The developed high-resolution MAM is a robust and qualified analytical strategy for therapeutic protein characterization.
• MAM provides enhanced capabilities for monitoring product quality attributes compared to conventional methods.
• The MAM-DoE approach offers significant operational flexibility and control in biopharmaceutical manufacturing.