DHS FF Series Centrifuge Bottle Filling System

Overview

The DHS FF Series Centrifuge Bottle Filling System is a purpose-engineered, aseptic liquid dispensing platform designed for high-integrity biopharmaceutical manufacturing environments. It addresses a critical process vulnerability in closed-system bioprocessing: the manual or semi-automated transfer of bulk drug substance or intermediate solutions into centrifuge bottles prior to centrifugal separation. Unlike general-purpose liquid handlers, the FF system operates on a gravimetric filling principle—leveraging high-resolution load cells and digital signal transmitters calibrated to ISO/IEC 17025 traceable standards—to deliver precise, repeatable, and auditable fill volumes under Grade A (ISO 5) or isolator-integrated conditions. Its architecture supports integration into end-to-end single-use or stainless-steel bioprocess trains, where it serves as a validated interface between upstream bioreactors or hold tanks and downstream centrifugation steps. The system complies with core principles of ICH Q5A, Q5B, and Annex 1 (2022), emphasizing containment integrity, material compatibility, and operational reproducibility during high-risk open manipulations.

Key Features

• Gravimetric filling accuracy of ±0.1% full-scale across all supported models (FF-16, FF-18, FF-26), achieved via dual-stage weighing: simultaneous tare-and-fill measurement of both centrifuge bottle and cap assembly prior to sealing
• Modular, fully replaceable fluid path system constructed exclusively from USP Class VI-certified silicone tubing; all wetted surfaces—including filling hood, bottle cradle, and valve manifolds—fabricated from electropolished 316L stainless steel or medical-grade PEEK and PTFE
• Patent-pending anti-foaming filling hood with laminar-flow–guided nozzle insertion and dynamic pressure compensation, minimizing shear-induced protein aggregation and air entrapment during viscous or surfactant-containing formulations
• PLC-based control architecture (Siemens S7-1200 series) compliant with ISA-88 and ISA-95 modular automation standards; supports deterministic cycle timing, batch event logging, and hardware-level interlock logic for door access, pressure differential, and sterilization status
• Large-bore main isolation valve (DN25) paired with precision bypass metering valves (CV ≤ 0.005) enabling rapid fill rates up to 120 mL/s while maintaining tight volumetric control across 5–500 mL fill ranges
• Pre-sterilized, gamma-irradiated (25 kGy) components shipped in ISO 11140-compliant barrier packaging; validation documentation includes V&V protocols aligned with ASTM E2500 and EU GMP Annex 15

Sample Compatibility & Compliance

The FF system accommodates standard conical-bottom centrifuge bottles (e.g., Thermo Fisher Nunc, Corning, Sarstedt) ranging from 15 mL to 250 mL nominal volume, including both screw-cap and snap-cap configurations. Bottle geometry recognition is mechanical—not vision-based—ensuring robust operation under low-light isolator conditions. All contact materials meet USP and cytotoxicity and systemic injection testing requirements. The system supports cleaning-in-place (CIP) with 0.5 M NaOH and steam-in-place (SIP) at 121°C/20 min when configured with autoclavable manifolds. Full compliance documentation includes ISO 13485:2016 quality management system certification, CE marking per Machinery Directive 2006/42/EC, and conformity to FDA 21 CFR Part 11 for electronic records and signatures when paired with optional audit-trail-enabled HMI firmware.

Software & Data Management

The embedded HMI provides real-time display of fill weight, deviation from target, cumulative batch count, and valve actuation cycles. All process data—including timestamped weight curves, alarm logs, and operator actions—are stored locally on encrypted industrial SSDs with redundant backup capability. Optional Ethernet/IP or OPC UA connectivity enables seamless integration with MES (e.g., Siemens Opcenter, Rockwell FactoryTalk) and LIMS platforms. Electronic batch records (EBR) generated by the system include digital signatures, change history, and immutable audit trails meeting ALCOA+ principles. Raw data export is available in CSV and ASTM E1382-compliant XML formats for regulatory submission.

Applications

• Fill-and-finish of cell culture harvests prior to clarification centrifugation in mAb, viral vector, and vaccine manufacturing
• Accurate dispensing of clarified lysates into ultracentrifuge tubes for density gradient purification
• Buffer exchange preps requiring high-precision volume allocation into swing-out rotor buckets
• GMP-compliant QC sampling of bulk intermediates under aseptic conditions without breaking primary containment
• Process validation studies supporting comparability assessments across scale-up batches (e.g., Phase II → III transition)

FAQ

Does the FF system support integration with existing SCADA or DCS infrastructure?

Yes—via configurable Modbus TCP or OPC UA server mode, with mapping tables provided for tag synchronization and alarm forwarding.
Can the system be qualified for use in Grade A environments inside an RABS or isolator?

Yes—the FF-18 and FF-26 models are dimensionally optimized for glove-port installation and include HEPA-filtered internal purge circuits compatible with ISO 14644-1 Class 5 airflow specifications.
What validation support is provided for initial commissioning?

DHS supplies IQ/OQ protocol templates, FAT/SAT checklists, and a complete URS cross-reference matrix; on-site PQ execution support is available under separate service agreement.
Is tubing replacement possible without specialized tools or calibration recalibration?

Yes—tube sets are pre-assembled on quick-disconnect manifolds; system auto-detects new assemblies and applies factory-stored flow compensation coefficients.
How is sterility assurance maintained during multi-batch operation?

Each fill cycle triggers automatic sterile flush with pre-validated WFI or saline; residual moisture detection via integrated capacitive sensors prevents carryover between batches.