An Intra-Company Analysis of Inherent Particles in Biologicals Shapes the Protein Particle Mitigation Strategy Across...

Area of Science:

• Biopharmaceutical Manufacturing
• Protein Chemistry
• Quality Control

Background:

• Protein aggregation and particle formation are critical challenges in biologics development.
• Understanding historical trends is essential for proactive mitigation strategies.

Purpose of the Study:

• To analyze historical protein particle issues within Novartis' biologics pipeline.
• To identify key themes and root causes associated with inherent particle formation.
• To establish a data-driven particle mitigation strategy.

Main Methods:

• Systematic collection and analysis of inherent particle occurrences over 10 years.
• Creation of a comprehensive protein particle database.
• Trending of product attributes against identified root causes.

Main Results:

• Non-monoclonal antibodies (non-mAbs) showed a higher propensity for particle formation than mAbs.
• Most particles were detected during large-scale manufacturing, not predicted by small-scale studies.
• Visible particles were the predominant issue, followed by subvisible particles; 50% were manufacturing-related.

Conclusions:

• Learnings from historical data form the basis of a new particle mitigation strategy.
• Preventive actions were developed to address manufacturing and product attributes.
• Transparent sharing of industry experiences with inherent particle formation is encouraged.