AKTA pcc Continuous Chromatography System

Overview

The AKTA pcc Continuous Chromatography System is a fully integrated, scalable platform engineered for continuous, multi-column protein purification under GMP-aligned operational conditions. Developed by Cytiva (Uppsala, Sweden), the system implements true periodic counter-current chromatography (PCC) principles—leveraging sequential column switching, dynamic load balancing, and real-time process adaptation to maintain consistent product quality across extended run times. Unlike batch-based systems, the AKTA pcc operates on a steady-state mass transfer model, where feedstock is continuously introduced while elution, washing, and regeneration occur in parallel across multiple columns. This architecture significantly improves resin utilization efficiency, reduces buffer consumption by up to 40% compared to conventional batch processes, and enables higher volumetric productivity without compromising purity or yield. The system supports both monoclonal antibodies (mAbs) and complex biologics—including bispecifics, Fc-fusion proteins, and viral vectors—making it suitable for clinical-stage manufacturing and commercial-scale purification workflows.

Key Features

• Modular column configuration with selectable 3-column or 4-column layouts, enabling flexible implementation of 2-column PCC, 3-column tandem loading, or 4-column full-cycle continuous operation.
• Dynamic process control engine that continuously monitors feed concentration (via inline UV/conductivity), column breakthrough profiles, and resin saturation status to auto-adjust loading volumes, wash durations, and elution triggers.
• Proprietary Post-Loading Wash (PLW) functionality—executed immediately after sample loading and prior to elution—which removes weakly bound impurities while retaining target product on resin, thereby enhancing final purity and increasing overall recovery by ≥5–8% relative to standard wash protocols.
• Integrated high-stability xenon lamp UV-Vis detector with dual-wavelength capability (254 nm and 280 nm), low-noise analog signal processing, and temperature-compensated baseline stability for reproducible quantitation across multi-day campaigns.
• Full suite of inline sensors: conductivity, pH, pressure (up to 20 bar), and temperature—with all signals sampled at ≥10 Hz and time-synchronized to chromatogram data.
• Robust fluidic architecture featuring low-dead-volume valves, PEEK/PEEK-lined tubing, and single-use-compatible flow paths validated for ≤0.2 µm sterile filtration integration.

Sample Compatibility & Compliance

The AKTA pcc accommodates a broad range of biomolecular feedstocks, including clarified mammalian cell culture harvests (e.g., CHO, HEK293), microbial lysates, and plasma-derived fractions. It supports standard chromatographic resins such as Protein A, ion exchange (IEX), hydrophobic interaction (HIC), and mixed-mode media—validated for use with resins from Cytiva, Tosoh, Bio-Rad, and Purolite. All hardware and software components are designed in alignment with ICH Q5A(R2), ICH Q5B, and USP guidelines for analytical instrument qualification. The UNICORN software platform provides audit trail, electronic signature, and user access control features compliant with FDA 21 CFR Part 11 and EU Annex 11 requirements. Full IQ/OQ documentation packages are available upon request, supporting regulatory submissions for Phase II/III clinical manufacturing and commercial license applications.

Software & Data Management

Control and monitoring are managed via UNICORN 7.4 or later—a validated, Windows-based chromatography software platform with native support for continuous process methods. Method development tools include automated gradient scouting, peak tracking across columns, and real-time overlay of multi-column chromatograms. All raw sensor data, method parameters, and event logs are stored in encrypted .chm binary format with SHA-256 hash integrity verification. Data export options include CSV, PDF report generation, and direct integration with LIMS and MES systems via OPC UA or RESTful API interfaces. Version-controlled method libraries, role-based permissions (Administrator, Operator, Reviewer), and configurable alarm thresholds ensure traceability and procedural consistency across shifts and sites.

Applications

• Continuous capture of monoclonal antibodies using Protein A chromatography—reducing cycle time by >50% versus batch mode while maintaining ≥99.5% monomer content per SEC-HPLC.
• Polishing steps involving sequential anion-exchange and hydrophobic interaction chromatography for host cell protein (HCP) and DNA clearance.
• Process intensification studies for biosimilar development, where residence time distribution modeling and column efficiency mapping inform scale-up decisions.
• Early-phase clinical material production requiring rapid turnaround and strict documentation adherence under GLP conditions.
• Technology transfer between R&D, pilot plant, and commercial facilities using identical UNICORN method templates and hardware configurations.

FAQ

What regulatory standards does the AKTA pcc support?
The system complies with FDA 21 CFR Part 11, EU Annex 11, ISO 13485, and ICH Q5A(R2) for biopharmaceutical manufacturing environments.
Can the AKTA pcc be integrated into existing downstream process skids?
Yes—it features standard 3/8″ VCR fittings, 4–20 mA analog I/O, and digital communication via Ethernet/IP or Modbus TCP for seamless integration with PLC-based control systems.
Is single-use fluidic path support available?
Cytiva offers validated single-use flow path kits for the AKTA pcc, including pre-sterilized tubing assemblies, column adapters, and sensor housings compatible with gamma irradiation sterilization.
How is method scalability ensured from lab to manufacturing scale?
UNICORN’s dimensionless parameter scaling tools preserve linear velocity, residence time, and binding capacity ratios—enabling direct translation of PCC methods from 1 mL/min to 100 mL/min systems without re-optimization.
Does the system support PAT (Process Analytical Technology) frameworks?
Yes—the integrated sensor suite, real-time data streaming, and UNICORN’s built-in multivariate analysis (MVA) module support QbD-aligned PAT implementation, including real-time release testing (RTRT) strategies.