A Quadrupole Dalton-based multi-attribute method for product characterization, process development, and quality...

Area of Science:

• Biopharmaceutical analysis
• Analytical chemistry
• Protein characterization

Background:

• Therapeutic proteins undergo post-translational modifications (PTMs) during manufacturing and storage.
• PTMs like isomerization, deamidation, and oxidation can impact protein bioactivity, stability, and pharmacokinetics/pharmacodynamics, classifying them as potential critical quality attributes (pCQAs).
• Traditional methods for PTM identification and control are time-consuming and costly, hindering Quality by Design (QbD) implementation.

Purpose of the Study:

• To develop and qualify a simplified, cost-effective multi-attribute method (MAM) for monitoring PTMs in therapeutic monoclonal antibodies.
• To assess the suitability of a Quadrupole Dalton (QDa) mass detector-based MAM for quality control (QC) environments.
• To demonstrate the method's utility in product and process characterization studies.

Main Methods:

• A multi-attribute method (MAM) was developed utilizing a Quadrupole Dalton (QDa) mass detector.
• The QDa-based MAM was employed to selectively monitor and quantitate post-translational modifications (PTMs) in a therapeutic monoclonal antibody.
• The method underwent qualification according to International Conference on Harmonization (ICH) guidelines and was applied to drug substance and stability samples.

Main Results:

• The QDa-based MAM provided straightforward and automatic results for PTM monitoring.
• Evaluation demonstrated comparable results to traditional analytical assays.
• The method was successfully qualified and applied to characterize drug substance and stability samples.

Conclusions:

• The QDa-based MAM is a QC-friendly and cost-effective tool for monitoring PTMs in therapeutic monoclonal antibodies.
• This method facilitates a facile understanding of process impacts on multiple quality attributes.
• The qualified QDa-based MAM is highly useful for product and process characterization in biopharmaceutical development.