Understanding the Options

Plasma Fractionation - IgG Hyperimmune

Clarification and Prefiltration

• Remove colloids, aggregated and non-product proteins, lipids and large particles
• Protect downstream sterilizing-grade filters, chromatography media and TFF membranes
• Must be able to withstand multiple steam-in-place or hot water sanitization cycles
• Run efficiently to ensure process economics

Recommended Filter	Filter Characteristics
Double-layer Millistak+ HC Filters (Grade C0HC) Disc Filters Pod Filters	Better suited for volumes <500 L or 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 so prefiltration may not be required. This can lower overall filtration costs. Although grade C0HC is ideal for this application, Millistak+ 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.
Single-layer Millistak+ DE Filters (Grade 75DE) Disc Filters Capsule Filters	Better suited for large volumes >500 L High internal surface area for maximum particle capture loading Graded density matrix allows retention of particle range High porosity provides low pressure drop Although grade 75DE is typical for this application, Millistak+ 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.
Double-layer Milligard Filters (Grade SS, 0.5 µm + 0.2 µm) Cartridge Filters Opticap Capsule Filters Optiscale Capsule Filters	Double-layer pleated configuration of mixed esters of cellulose membranes provide high dirt-holding capacity and retention efficiency High porosity membranes operate at high flow rates and low pressure drops Non-fiber releasing structure preserves product purity 100% integrity tested to ensure quality Robust construction validated to withstand multiple SIP or hot water sanitization cycles Although grade SS is commonly used for this application, Milligard filters are available in numerous pore sizes and in double-layer or triple-layer configurations to accommodate the needs of each user, the degree of protection required for the downstream process and the plugging characteristics of the fluid. Choice should be based on small-scale testing.

Viral Clearance

• Critical step to ensure removal of viruses known to have contaminated source plasma such as parvovirus, hepatitis viruses and HIV
• Following current regulatory guidelines, 2 orthogonal methods are normally utilized to remove or inactivate viruses
• Validated log removal of viruses is a dedicated process step
• Filtration products should easily scale-up and down for simple validation

Recommended Filter	Filter Characteristics
Viresolve NFR Filters	>6 log removal of retroviruses (80–120 nm) >98% recovery of protein (IgG) 100% Integrity testing assures performance Robust PES membrane Can be integrity tested on-site
Viresolve NFP Filters	>4 log removal of parvovirus and other small viruses >98% recovery of protein up to 160kD Robust PVDF membrane 100% Integrity testing assures performance Can be integrity tested on-site To enhance filter performance and capacity, Millipore suggests using the Viresolve Prefilter in series.

Ultrafiltration

• Reduce batch volumes and exchange buffer systems for efficient column operation and final formulation
• Run efficiently to ensure process economic

Recommended Filter

Filter Characteristics

Pellicon Cassettes with Biomax 30 kD Membrane or Ultracel PLC 30 kD Membrane

Low feed flow requirement minimizes pumping, working and hold up volumes Higher product recovery and flux Highly retentive void-free membranes offer good permeate flux and withstand process upsets Robust low binding void-free Ultracel PLC membranes provide excellent repeat performance Choose a membrane molecular weight cut-off 3–5X smaller than the biomolecule. Choice should be based on small-scale testing.

Sterile Filtration (Also see Aseptic Filling)

• Sterilizing-grade filters reduce bioburden and sterilize heat labile proteins
• Must be able to withstand multiple steam-in-place or hot water sanitization cycles
• Run efficiently to ensure process economics

Recommended Filter	Filter Characteristics
Durapore 0.22 µm Filters Cartridge Filters Optiseal Cartridge Filters Opticap Capsule Filters Optiseal Capsule Fitlers	Sterilizing-grade PVDF low-binding membrane is ideal when adsorption is a concern 100% Integrity testing and thousands of existing applications assure proven performance 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. Integrity testable on-site
Millipore Express 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 even with clogging streams Can be integrity tested on-site Available in single-layer 0.2 µm (SHF) or double-layer 0.5 µm + 0.2 µm (SHC) configurations. 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.