Cytiva AKTAcrossflow Automated Tangential Flow Filtration (TFF) System

Overview

The Cytiva AKTAcrossflow Automated Tangential Flow Filtration (TFF) System is an integrated, benchtop-scale platform engineered for precise, reproducible, and scalable tangential flow filtration operations across the bioprocessing workflow—from mammalian or microbial cell harvest through concentration, diafiltration (DF), and final buffer exchange of therapeutic proteins, antibodies, and viral vectors. Based on the well-established hydrodynamic principle of crossflow—where feed stream velocity parallel to the membrane surface minimizes fouling and maintains stable flux—the AKTAcrossflow system delivers deterministic control over transmembrane pressure (TMP), retentate recirculation rate, permeate collection, and volume reduction factor (VRF). Its architecture enables seamless integration with Cytiva’s ÄKTA chromatography platforms via shared UNICORN software infrastructure, allowing coordinated execution of hybrid purification strategies (e.g., TFF-coupled capture or polishing steps) within a single method file.

Key Features

• Automated, programmable control of all critical TFF parameters—including feed pump speed, permeate valve actuation, TMP regulation, and real-time volume tracking—via UNICORN software interface.
• Modular fluid path design supporting both cassette-based ultrafiltration (UF) and hollow-fiber microfiltration (MF), with compatibility for up to three 50 cm² cassettes in parallel (max. 150 cm² total area).
• Innovative peristaltic-plus-diaphragm hybrid pump system delivering pulse-free flow, low shear stress (< 100 s⁻¹ nominal), and precise volumetric accuracy (±2% of setpoint) across 25–2,000 mL working volumes.
• Sanitary-grade 316L stainless-steel wetted components and USP Class VI-certified tubing ensure compliance with ISO 13485 and EU Annex 1 requirements for early-phase biomanufacturing environments.
• Preloaded, validated cleaning-in-place (CIP) and sanitization-in-place (SIP) methods—including NaOH, citric acid, and ethanol protocols—accessible via UNICORN’s Method Wizard.
• Real-time flux scouting mode: automatically sweeps transmembrane pressure (0.1–3.0 bar) and crossflow velocity (0.1–1.5 m/s) to identify optimal operating conditions within <90 seconds per condition.

Sample Compatibility & Compliance

The AKTAcrossflow system accommodates a broad range of biomolecular samples, including clarified cell culture harvests (0.1–20% solids), monoclonal antibody (mAb) pools, virus-like particles (VLPs), mRNA-LNPs, and fragmented DNA preparations. It supports membranes with molecular weight cut-offs (MWCO) from 1 kDa (tight UF) to 0.2 µm (sterile-grade MF), including Cytiva’s Start™ hollow-fiber cartridges (AXM series, 30 cm length; AXH series, 60 cm length) and Repligen® KrosFlo® iCELLis® cassettes. All operational logs, method versions, user actions, and electronic signatures are recorded with time-stamped, immutable audit trails—fully compliant with FDA 21 CFR Part 11 when deployed with UNICORN Pharma Edition and appropriate system validation documentation. The platform meets ICH Q5A(R2) and Q5D requirements for viral clearance validation studies involving TFF-based separation steps.

Software & Data Management

UNICORN software (v7.4 or higher) serves as the unified control and data management layer for AKTAcrossflow. It provides graphical method editing, real-time trending of flux, TMP, conductivity, pH (with optional probes), and cumulative permeate volume. Raw sensor data is stored in native .cdt format with embedded metadata (method name, operator ID, timestamp, instrument serial number), enabling traceability across development batches. Batch reports auto-generate PDF summaries compliant with ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, Available). Data export supports CSV, Excel, and SDTM-compliant formats for integration into LIMS or statistical process control (SPC) systems such as JMP or Minitab.

Applications

• Early-stage process development: rapid screening of membrane types, MWCOs, and operating conditions to define robust TFF operating envelopes.
• Cell harvest optimization: clarification of CHO, HEK293, or microbial lysates using Start AXM hollow-fiber cartridges with 0.45–0.65 µm pores.
• Antibody concentration and buffer exchange: UF/DF of mAbs from 5–20 g/L to >100 g/L with minimal aggregation (<2% increase in HMW species by SEC-HPLC).
• Viral vector processing: gentle concentration of AAV or lentivirus preps using low-shear cassettes with 100–500 kDa MWCO.
• Scale-down model qualification: correlation of AKTAcrossflow performance (flux decay, rejection rate, VRF) with production-scale TFF skids using dimensionless scaling parameters (e.g., Reynolds number, shear rate).

FAQ

Can the AKTAcrossflow system be used for sterile filtration of final drug substance?
No—it is not designed for terminal sterilization-grade filtration. It supports sterile-grade microfiltration (0.2 µm) during upstream processing but requires downstream sterilizing-grade filtration (e.g., 0.22 µm PVDF) prior to fill-finish.
Is remote monitoring supported?
Yes—UNICORN Remote Access enables secure, browser-based monitoring and limited control (pause/resume, alarm acknowledgment) via corporate intranet or VPN.
What validation documentation is provided?
Cytiva supplies Factory Acceptance Test (FAT) reports, Installation Qualification (IQ) templates, and Operational Qualification (OQ) test scripts aligned with ASTM E2500 and ISPE GAMP5 guidelines.
Does the system support single-use fluid paths?
Yes—compatible with disposable tubing sets, cassettes, and hollow-fiber cartridges; wetted parts can be fully replaced without tools.
How is system calibration performed?
Flow rate calibration uses gravimetric verification against NIST-traceable balances; pressure sensors are factory-calibrated and field-verifiable using dead-weight testers.