Pure-Bio Flux Tangential Filtration Systems
Pure-Bio Flux Tangential Filtration Systems
Introducton
Pure-BioFlux™ TFF System– A Tangential Flow Filtration (TFF), also referred to as crossflow filtration, is a cornerstone technology in modern biomanufacturing. At the manufacturing scale, TFF systems are designed to process hundreds to thousands of litres of biopharmaceutical feed streams, providing critical separation, concentration, and buffer exchange capabilities. These systems are indispensable for the downstream processing of monoclonal antibodies (mAbs), recombinant proteins, vaccines, viral vectors, plasmid DNA, and biosimilars.
Pure-BioFlux™ TFF System– A Tangential Flow Filtration (TFF), also referred to as crossflow filtration, is a cornerstone technology in modern biomanufacturing. At the manufacturing scale, TFF systems are designed to process hundreds to thousands of litres of biopharmaceutical feed streams, providing critical separation, concentration, and buffer exchange capabilities. These systems are indispensable for the downstream processing of monoclonal antibodies (mAbs), recombinant proteins, vaccines, viral vectors, plasmid DNA, and biosimilars.
The system integrates advanced control logic, process analytical technology (PAT), and modular skid design to enable efficient, reproducible, and validated ultrafiltration/diafiltration (UF/DF) processes. It supports batch, fed-batch, and continuous operations, positioning it as a flexible solution for today’s dynamic biopharmaceutical industry.
Unlike dead-end filtration, where feed passes perpendicularly through the membrane surface leading to rapid fouling, TFF operates by circulating the feed solution tangentially across the membrane surface. This design minimizes fouling, maintains high flux, and allows continuous removal of permeate while retaining macromolecules of interest.
Key performance factors include:
• Transmembrane Pressure (TMP): Driving force for filtration, controlled to balance flux and fouling.
• Crossflow Velocity (Shear): Prevents concentration polarization and fouling.
• Membrane Cut-Off (MWCO): Determines separation selectivity.
Applications in Biomanufacturing
• Monoclonal antibodies (mAbs): Concentration and buffer exchange.
• Insulin and biosimilars: Purification and polishing.
• Vaccines: Removal of contaminants, concentration of viral particles.
• Gene therapies: Plasmid DNA and viral vector purification.
• Enzymes and recombinant proteins: Final concentration and formulation.
Advantages of TFF
• High scalability (from lab to 2000 L+ scale).
• Continuous or batch-compatible operation
• High product recovery (>95% typical).
• Gentle handling of shear-sensitive biomolecules.
• Compliance with cGMP and regulatory standards.
System Description
The Pure-BioFlux TFF system is designed as a modular skid-mounted platform, built with GMP-grade stainless steel and/or hybrid stainless steel–single-use assemblies depending on the application. It comprises:
• Membrane modules (cassettes or hollow fibers) with surface areas ranging from 0.5 m² to 100 m²+ for large-scale processes.
• Pumps (feed, retentate, and diafiltration buffer) with precision control to maintain constant TMP and shear conditions.
• Instrumentation including pressure transducers, conductivity sensors, pH sensors, and optional UV detectors for real-time monitoring.
• Control system with PLC, HMI, and SCADA integration for recipe-driven automation, data logging, and electronic batch records.
• CIP/SIP functionality ensuring cleaning validation and system sterility.
The system supports both stainless-steel reusable membrane cassettes and single-use TFF flow paths depending on user requirements.
System Components
Pumps
• Feed Pump: Typically, a positive displacement diaphragm or peristaltic pump capable of handling large volumes with minimal shear.
• Retentate Pump: Circulates the feed tangentially across the membrane.
• Diafiltration Buffer Pump: Delivers precise buffer volumes for controlled diafiltration cycles.
Membrane Modules
• Configurable with cassette-based UF/DF membranes or hollow Fiber modules.
• Membrane cut-offs: 1 kDa – 1,000 kDa depending on application.
• Surface area scalability: 0.5 m² (pilot) to 100 m²+ (manufacturing).
Control System
• PLC (Programmable Logic Controller) with 21 CFR Part 11-compliant HMI.
• Data integrity ensured with audit trails, electronic signatures, and alarm management.
• Recipe management for multiple product campaigns.
Instrumentation
• Pressure sensors (inlet, retentate, permeate).
• Flow meters (Coriolis or mag flow).
• Temperature, conductivity, UV, and pH sensors.
• Data logging and trending via SCADA.
Cleaning & Sterilization
• Automated CIP/SIP cycles integrated into recipes.
• Compatibility with NaOH, detergents, and sanitizing agents.
• Temperature, conductivity, UV, and pH sensors.
• Steam sterilization of wetted parts (for stainless-steel flow paths).
| Operating Parameters | Value |
|---|---|
| Feed Flow Rate | 5 – 200 L/min (depending on pump selection) |
| Operating Volume | 100 L to 2000 L+ (scalable) |
| Diafiltration Volume | 1 – 20 DV (customizable) |
| pH Range | 3 – 12 (short-term exposure up to pH 13–14) |
| TMP Range | 0.5 – 3 bar typical (configurable) |
| Concentration Factor (CF) | Up to 20x or higher |
| Operating Temperature | 4 – 40 °C |
Performance Characteristics
• High Product Recovery: >95% typical.
• Scalability: Linear scale-up from lab to manufacturing scale with similar hydrodynamic conditions.
• Cycle Time: 4 – 8 hours typical for mAb concentration and diafiltration.
• Flux Rate: 20 – 100 LMH (Liters per m² per hour).
• Cleaning Efficiency: >99% flux recovery after validated CIP.
System Integration in Biomanufacturing
The TFF skid is designed for seamless integration with:
• Upstream: Harvested cell culture fluid clarification and bulk buffer systems.
• Downstream: Chromatography skids, virus filtration systems, formulation tanks.
• Automation: Distributed Control Systems (DCS), PAT analysers, Manufacturing Execution Systems (MES).
The system can operate in batch, fed-batch, or continuous filtration modes, supporting both traditional stainless-steel manufacturing and emerging single-use, flexible facilities.
General Technical Specifications of Manufacturing-Scale TFF System
| Parameter | Specification |
|---|---|
| System Capacity | 100 L – 2000 L+ (scalable) |
| Pump Type | Positive displacement diaphragm/peristaltic |
| Membrane Module | Cassette (UF/DF, spiral wound) or hollow fiber |
| Membrane Surface Area | 0.5 – 100 m²+ |
| MWCO Range | 1 kDa – 1,000 kDa |
| TMP Range | 0.5 – 3 bar |
| Operating Flow Rate | 5 – 200 L/min |
| Diafiltration Volume | 1 – 20 DV (customizable) |
| Product Recovery | >95% typical |
| Flux Range | 20 – 100 LMH |
| Control System | PLC + HMI, 21 CFR Part 11 compliant |
| Data Integrity | Audit trail, e-signatures, batch reporting |
| Cleaning Capability | CIP/SIP automated |
| Materials of Construction | 316L stainless steel, EPDM/PTFE gaskets, pharma-grade polymers (for single-use) |
| Regulatory Compliance | cGMP, ASME BPE, ISPE, FDA/EMA guidelines, CE, 21 CFR Part 11 |
| Utilities Required | Clean steam, WFI, compressed air, electricity (400V/230V configurable) |
Compliance and Standards
A Pure-BioFlux™ TFF system must operate under stringent compliance frameworks to meet international regulatory expectations. The following standards and guidelines form the foundation of design, qualification, and operation.
Regulatory Compliance
• cGMP (current Good Manufacturing Practice): Ensures product quality, safety, and reproducibility.
• FDA (21 CFR): Particularly Part 210/211 (drug manufacturing), Part 600 (biologics), and Part 11 (electronic records & signatures).
• EMA Guidelines: Annex 1 for sterile manufacturing and EudraLex Volume 4 for GMP compliance.
• ICH Q8–Q10: Emphasizing quality by design (QbD), risk management, and continuous improvement.
Engineering Standards
• ASME-BPE: Bioprocessing equipment design for hygienic applications.
• ISPE Baseline Guides: For biopharmaceutical facilities and equipment design.
• ISO 13485 & ISO 9001: Quality management for medical and biotech equipment.
• CE Marking: For electrical and mechanical safety compliance within the EU.
Data Integrity and Part 11 Compliance
The control system is equipped with:
• Audit trails: Secure, tamper-proof records of operator actions
• Electronic signatures: For process approvals.
• Batch records: Automatically generated with process parameters and alarms.
• User access control: Multi-level security with password protection.
Compliance Overview
| Compliance Area | Standard / Guideline | System Feature |
|---|---|---|
| cGMP | FDA, EMA, WHO | Hygienic design, validation, reproducible operation |
| Electronic Records | 21 CFR Part 11 | Audit trail, e-signature, secure batch reporting |
| Bioprocessing Equipment | ASME-BPE, ISPE | 316L stainless steel, polished surfaces, cleanability |
| Electrical Safety | CE Marking, IEC Standards | Electrical enclosures, interlocks, emergency stops |
| Quality Management | ISO 9001, ISO 13485 | Documented QMS, validated software |
| Data Integrity | ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate) | Full SCADA integration with secure data storage |
Kindly be in touch with Sales/Technical personnel for more information