Understanding the Options

Mammalian Cell Culture Clarification

Primary Clarification

• Removes whole cells and solids from bioreactor fluid and recover product in filtrate
• Requires high capacity
• Wide feed stream variability depending on cell culture type and conditions
• If solid content is too high, centrifugation becomes preferred technology

Recommended Filter	Filter Characteristics
Prostak Open-Channel Modules with 0.22 µm or 0.65 µm Durapore Membrane	For bioreactors volumes up to 1,000 L or larger volumes with low usage rates of less than 10 batches/year Double layer design enhances loading capacity and filtrate quality Unique configuration allows compression of multiple process steps into one, lowering overall filtration costs. Selection of C0HC or D0HC media grade depends on particle size distribution in feed solution. Choice should be based upon small-scale testing.
Prostak Open-Channel Modules with 0.22 µm or 0.65 µm Durapore Membrane	Best suited for large bioreactors >1,000 L or bioreactors with high usage rates of more than 10 batches/year Open-channel design accommodates fluids containing low to medium cell density and solids High flux at low transmembrane pressure Robust construction allows multiple use Validated for multiple SIP cycles Selection of 0.22 µm or 0.65 µm membrane depends on particle size distribution in feed solution. Choice should be based upon small-scale testing.

Secondary Clarification or Polishing

• Feed stream quality can vary depending on cell type, culture conditions, and primary clarification technology

Recommended Filter

Filter Characteristics

Triple-layer Millistak+ HC Filters (Grade A1HC or B1HC) Disc Filters Pod Filters

Triple-layer configuration includes a membrane bottom layer to enhance filter loading capacity and retention High filtrate quality allows smaller size requirements for downstream sterilizing-grade filtration step Unique design enables the compression of multiple process steps into one, lowering overall filtration costs The selection of grade A1HC or B1HC depends on the fluid particle size distribution and should be based on small-scale testing.

Bioburden Reduction

• Reduces bioburden
• Protects downstream chromatography and UF/DF steps
• Maintains yield of dilute protein and preserves purity
• Sterilizing-grade filtration recommended

Recommended Filter	Filter Characteristics
Single-layer Durapore 0.22 µm PVDF Filters Cartridge Filters Optiseal Cartridge Filters Opticap Capsule Filters Optiseal Capsule Fitlers	Sterilizing-grade low-protein binding PVDF membrane 100% Integrity testing to ensure performance Can be integrity testable on-site Although 0.22 µm is typical for this application, Durapore filters are available in several pore sizes and, in single-layer or multi-layer configurations to accommodate the degree of protection required for the downstream process and the plugging characteristics of the fluid. Choice should be based on small-scale testing.
Millipore Express SHC 0.5 µm + 0.2 µm PES Filters Cartridge Filters Opticap Capsules Optiscale Capsules	Sterilizing-grade PES membrane providing broad chemical compatibility across a wide pH range (1–14) Robust construction validated for multiple SIP cycles 100% integrity tested to ensure quality Asymmetric pore structure delivers extremely high flow rates at low pressure drop Can be integrity tested on-site Although double-layer 0.5 µm + 0.2 µm (SHC) is typical for this application, single-layer 0.2 µm (SHF) filters are available. The degree of protection required for the downstream process and the plugging characteristics of the fluid will guide this selection. Choice should be based on small-scale testing.