Filtration membranes - Scavengers for leachables?

Area of Science:

• Biopharmaceutical Manufacturing
• Filtration Technology
• Analytical Chemistry

Background:

• Leachables pose risks in biopharmaceutical production.
• Sterile filtration is a critical downstream process.
• Filter materials may interact with process fluids.

Purpose of the Study:

• To investigate the leachable scavenging potential of common sterile filter materials.
• To quantify the capacity of filters for removing model leachable compounds.
• To assess the impact of filter type and leachable structure on scavenging.

Main Methods:

• Development of an experimental setup and testing protocol.
• Filtration of a model leachable mixture through polyethersulfone (PESU) and cellulose acetate (CA) filters.
• Quantification of leachables using High-Performance Liquid Chromatography with Ultraviolet detection (HPLC-UV).
• Mass balance determination by eluting leachables from filters with organic solvents.
• Determination of breakthrough curves and substance-specific filter capacities.
• Cell-culture bioassay to evaluate the impact of a specific leachable (bDtBPP).

Main Results:

• PESU and CA filters demonstrated efficient scavenging of model leachables.
• Scavenging efficiency varied based on leachable molecular structure and filter type.
• Substance-specific filter capacities ranged from <0.7 to 45 μg/cm².
• Analytical and cell-culture methods yielded comparable results for bDtBPP filter capacity.
• Extrapolation suggests significant leachable removal in large-scale filtration.

Conclusions:

• Sterile filters act as effective scavengers for process-related leachables.
• Filter material selection can optimize leachable removal in downstream processes.
• The scavenging capacity of filters should be considered in process design and risk assessment.