Ultrafiltration (UF) Membranes for Bioprocessing: Selection, Specification, and SepraPor® Hollow Fiber Options

What Ultrafiltration Does in Bioprocessing

Ultrafiltration separates molecules by size. A semi-permeable membrane retains molecules larger than its pore rating while water, salts, and small solutes pass through as permeate. In bioprocessing, UF concentrates proteins, monoclonal antibodies, plasmid DNA, and viral vectors. It also exchanges one buffer for another in the same operation.

UF typically sits after clarification and before chromatography or final formulation. A single UF/DF step handles volume reduction and buffer exchange, which is why it appears so often in drug substance and drug product workflows.

How Molecular Weight Cut-Off Is Assigned

Molecular weight cut-off (MWCO) is the membrane’s nominal rating, expressed in kilodaltons (kDa). It marks the molecular weight at which the membrane retains about 90% of a reference globular protein. Real membranes have a distribution of pore sizes, so molecules near the rating pass partially.

Characterization method determines how much confidence a rating deserves. Meissner characterizes SepraPor® UF membranes with a continuum of polymer standards of increasing molecular weight. Each MWCO is assigned a specific retention range instead of a single point value. The method also drove process control changes in hollow fiber manufacturing, which improves lot-to-lot reproducibility.

A common starting point sets MWCO at roughly one-third to one-sixth of the target molecule’s molecular weight. For a 150 kDa antibody, a 30 kDa or 50 kDa membrane retains product while passing buffer components. Confirm the choice with a retention study using your actual feed, measuring product in both permeate and retentate.

Hollow Fiber Format and TFF Operation

SepraPor® UF filters are hollow fiber tangential flow filtration (TFF) devices. Feed flows through the fiber lumen while permeate passes through the fiber wall. Typical fiber lumen is 1.0 mm internal diameter with 1.5 mm outer diameter.

Cross-flow sweeps retained material away from the membrane surface. This limits concentration polarization and cake buildup, which keeps flux higher across the run than dead-end filtration allows. Transmembrane pressure drives permeate flow until polarization or fouling limits it. Feed concentration rises during concentration, increasing viscosity and reducing achievable flux.

Meissner has published a UF/DF case study comparing hollow fibers with cassettes for plasmid DNA purification. Format selection affects footprint, hold-up volume, and how the system scales, so compare formats against your own process volume and recovery targets.

SepraPor® Product Line

SepraPor® XFM cartridges

• Format: hollow fiber TFF cartridge
• MWCO: 30, 50, 300, and 500 kDa on current spec sheets
• Scale: bench through production
• Installation: stainless steel housing with Cartridge Insertion Tool

SepraPor® XFC capsules

• Format: hollow fiber TFF capsule
• MWCO: 30 kDa documented
• Scale: bench through production

SepraPor® Process Ready Assemblies

• Format: gamma-sterilized capsule assemblies
• MWCO range: 10 to 750 kDa
• Membrane area: 13 cm² to 2.1 m²
• Connections: AseptiQuik® S/G
• Shipped glycerol-free, eliminating the IPA soak
• Wetting fluids: 1% H₂O₂ and DI water

Glycerol-free shipment removes the IPA soak step, which significantly reduces flushing time before use.

Materials of Construction

• Hollow fiber membrane: polysulfone
• Fiber bundle netting: polypropylene
• Fiber encapsulation: epoxy
• O-rings: silicone (XFM300, XFM500)
• Capsule housing: polysulfone
• All components animal component free (ACF)

Food contact compliance references: 21 CFR 177.1655 (polysulfone), 177.1520 (polypropylene), 175.300 (epoxy), and 177.2600 (silicone).

Operating Limits

Operating limits vary by part number and assembly format. The values below come from current SepraPor® spec sheets.*

Parameter	Value
Operating temperature	0 to 38 °C (32 to 100 °F)
Short-term cleaning temperature	50 °C (122 °F) maximum
Maximum feed pressure (XFM050, XFC30)	65 psig at 77 °F
Maximum TMP (XFM050, XFM300, XFM500)	45 psig at 77 °F
Maximum TMP (XFC30)	50 psig at 77 °F
Assembly maximum feed pressure	42 to 60 psig
Assembly maximum permeate pressure	10 psig

*Confirm limits against the spec sheet for your part number before setting process parameters.

Sanitization and Sterilization

SepraPor® filters withstand gamma irradiation, autoclave, steam-in-place (SIP), and chemical sanitization. Process Ready Assemblies arrive gamma-sterilized for single-use applications. Reusable cartridges and capsules follow the sterilization procedures in the SepraPor® Green Docs.

Rinsing and Integrity Testing

New filters require rinsing before integrity testing, sterilization, sanitization, or direct use. Meissner’s procedure specifies rinsing at 5 psi feed pressure for at least 5 minutes.

Bubble point and diffusive flow tests verify membrane integrity without damaging the membrane. Meissner performs these tests on its AccuFlux® integrity tester. Every filter is 100% integrity tested during manufacture, and assemblies are integrity tested before release. Acceptance criteria are defined in the Green Docs integrity procedure. For test values using wetting fluids other than those specified in the procedure, contact Meissner.

Documentation and Compliance

• Certificate of Conformance: supplied with SepraPor® filters
• Certificates of Quality and Conformance: supplied with assemblies
• USP 43 <87> biological reactivity testing
• Sterility verification per ANSI/AAMI/ISO 11137 for assemblies
• Quality Assurance audits of manufacturing conformance
• Additional technical data: meissner.com/green-docs

Request extractables and leachables data for your specific filter and tubing combination. Meissner documents for this are not publicly listed.

Specifying a UF Filter for Your Process

1. Define the target molecule and its molecular weight.
2. Document feed composition, pH, and ionic strength.
3. Set the required concentration factor and diavolume count.
4. Select the format: cartridge, capsule, or assembly.
5. Calculate membrane area from throughput and flux targets.
6. Confirm feed pressure, TMP, and temperature limits against the spec sheet.
7. Choose the sterilization method and rinse protocol.
8. Define the integrity test method and acceptance criteria.
9. List required documentation, including extractables and leachables.

Retention data for the selected MWCO, tied to a characterized lot, lets process results trace back to a defined membrane rating rather than a nominal value.