Extended Characterization and Impact of Visible Fatty Acid Particles - A Case Study With a mAb Product

Area of Science:

• Biopharmaceutical formulation analysis
• Protein aggregation and degradation studies
• Drug product quality and safety assessment

Background:

• Increased scrutiny on product-related particles in biopharmaceuticals.
• Challenges in identifying and characterizing fragile particles.
• Complex mechanisms of particle formation and impact on safety.

Purpose of the Study:

• Investigate the formation of visible particles from polysorbate 20 degradation in a monoclonal antibody (mAb-A) formulation.
• Characterize the identity and composition of these particles over time.
• Evaluate the behavior of visible particles upon exposure to saline and human plasma.

Main Methods:

• Raman spectroscopy for particle identification (free fatty acids).
• Mass spectrometry for monitoring particle composition over time.
• Flow imaging microscopy for subvisible particle analysis (counts and morphology).

Main Results:

• Visible particles were identified as free fatty acids (FFA) resulting from polysorbate 20 degradation.
• Particle composition and prevalence were monitored across different batch ages.
• Subvisible particle characteristics were quantified, and visible particle behavior in physiological fluids was assessed.

Conclusions:

• The study elucidates the formation pathway of visible particles from surfactant degradation in mAb formulations.
• Characterization methods provide insights into particle identity, composition, and fate.
• Findings support risk assessments for visible product-related particles in biopharmaceutical drug products.