Ambr 250 HT or Equal - Technical Specification Requirements.pdf

Technical Specification Requirements for High Throughput Scale-Down Model Bioreactor System for Process Development

Project Title: Ambr 250 or Equal High Throughput Bioreactor System for NIAID VPP

Introduction: The National Institute of Allergy & Infectious Diseases (NIAID), Vaccine Research Center (VRC), Vaccine Production Program (VPP) has a requirement to procure two (2) high-throughput, scalable, single-use bioreactor systems suitable for both perfusion and standard fed-batch cell culture processes for its mission to create vaccines. The systems must offer individual bioreactor control for Design of Experiments (DOE) optimization and enable precise, automated operations. Specifications should be Brand Name or Equal to a Sartorius Ambr 250 high-throughput bioreactor system.

Scope: The required bioreactor system should be capable of handling high-throughput operations and must include components and software optimized for efficient and consistent process development.

Product Requirements:

1. Bioreactor System Overview:

o Must be a high throughput, 24-way, scale-down model designed for process development.

o Suitable for both perfusion and standard fed-batch cell culture processes.

o Should provide individual bioreactor control for DOE optimization.

o Capable of integrating automated sampling with at-line analysis options for pH, cell count, or metabolite analysis.

o Capable of inputting processes algorithms for Design of Experiments (DOE) protocols.

2. Must be compatible with the following consumables o Single-Use Perfusion Bioreactor Vessels:

1. Fully assembled, irradiated, and ready to use to minimize setup and turnaround time.

2. Must include industry standard hollow fibre membranes (0.2 µm or 30 kDa, PES, Spectrum) for accurate large-scale process performance prediction.

3. Single-use pressure sensors for monitoring transmembrane pressure

(TMP).

o Perfusion Towers:

1. Support and control perfusion pump chambers, pinch valve cassette, and perfusion filter.

o Flow Control and Collection System:

1. Includes perfusion crossflow and permeate pumps.

2. Automated bleed functions.

3. Collection sets with bags and tubing management features for both permeate and bleed fluids.

4. Walk-away permeate sampling system for samples up to 10 mL.

3. Liquid Handling Unit:

o Facilitates addition of media, feed, cells, and reagents.

o Capable of sampling from bioreactor vessels using either 10 mL or 300 µL pipettes.

o Transfer samples to deck locations or integrated analyzers.

4. Control Software:

o User interface optimized for protocol configuration, control, and visualization of multiple parallel bioreactors.

o Full control over individual bioreactors.

Performance Specifications:

1. High Productivity System:

o Automation must enable a single user to conduct multiple bioreactor experiments, including DOE.

o Single-use bioreactors must reduce operator time needed for cleaning and setup.

2. Space and Facility Efficiency:

o Compact design with a minimal laboratory footprint.

o Single-use bioreactors must reduce the need for bioreactor wash-up and autoclaving.

o Working area is equivalent to a Class II Biosafety Cabinet (BSC) interior.

3. Size Specifications for 24-way system (excluding control PC, chiller, and UPS):

o Length: 400 cm o Depth: 115 cm o Height: 249 cm

4. Consistency and Reliability:

o Automated control and liquid addition to reduce variation and human error.

o Consistent data sets for better analysis and decision-making.

o Supports automatic clean-in-place (CIP).

5. Automated Sampling:

o Aseptic pipetting to reduce operator time significantly.

o Integration with at-line analyzers for pH, cell count, and metabolite analysis.

(existing ViCell Blu and NovaFlex II instruments).

6. SCADA integration:

o Must be able to be integrated into Program’s current system which is Lucullus.

Minimum Technical Requirements

• The systems must be free standing and complete with integrated biosafety cabinet (BSC) capable of maintaining a sterile environment.

• Each unit must have a length no greater than 400cm (13ft 2in) and a depth of not more than 115 cm (3ft 10 in), and a height not more than 249 cm (8 ft 2in) excluding, space for PC, chiller, and other ancillary equipment.

• Works on available power, 3 phase (plus neutral and primary earth) 380-44 VAC (phase to phase, 50/60Hz and capable of a minimum of 15A per phase and have an electrical disconnect isolator.

• Both systems must possess the ability to be hardwired.

• Both Systems must include a chiller which operates on 230 V supply @50 Hz with rated load current of approximately 8.8 AMPs.

• Each system must have ability to support unlubricated oxygen, nitrogen, and carbon dioxide supplies between 1.5 to 2 bar (20-29 psi).

• Perfusion system must allow for up to 3.5 bar compressed air inlet to instrument via supplied 6mm OD polyurethane tubing.

• Stirred tank system must allow for up to 2 bar compressed air inlet to instrument via supplied 6mm OD polyurethan tubing.

• Operable with currently stocked materials1 in support of multiple simultaneous small scale (~200 mL) bioreactor operation must support incoming technologies.

• Capable of operating between 1 and 24 bioreactors in parallel.

• Individualized bioreactor setup where each bioreactor functions as an individual module.

• Capable of supporting different growth conditions in parallel bioreactors, to include gassing, feed distribution, pH control, and dO at a minimum.

• Possesses disposable bioreactors and disposable sensors.

• Bioreactor working volume between 100 mL and 250 mL.

• Fully configurable sparge gassing.

• Fully configurable headspace gassing.

• Automated additions and sampling using disposable tips.

• Minimum of 4 liquid feed lines.

• 4 feed pumps per bioreactor.

• Capable of automatic foam detection.

• Capable of supporting mammalian cell culture and microbial cell culture.

• Working area is equivalent to a Class II Biosafety Cabinet (BSC) interior.

• Mammalian bioreactors 120 mm tall and 60 mm wide and utilize build-in pitched blade impeller 26 mm in diameter and 17 mm above bottom of bioreactor, sparge tube, glass pH electrode, 4 line liquid manifold, condensing ring, and access cap for disposable tips.

• Supports fully automated inoculation.

• Support real-time independent control of each bioreactor.

• Capable of defining media batch in all bioreactors.

• Capable of inputting processes algorithms for parameter control.

• Capable of inputting processes algorithms for Design of Experiments (DOE) protocols.

• Agitation speed between 150 rpm and 4500 rpm.

• Support culture temperature control in a range of 18 C to 55 C.

• Supports pH control in a range of 2 to 8.5 (+ 0.01 pH unit).

• Supports DO control in a range of 0 - 200 % (+ 5 %) air saturation.

• Sparge Gas flow rate up to 550 mL/min.

• CO2 Exhaust gas 0 - 20 %.

• O2 Exhaust gas 0 - 50 %.

• Maximum flow rate with in-line filters of at least 15 mL/min.

• Maximum flow rate without in-line filters of at least 115 mL/min.

• Disposable pipette bolus additions between 30 uL and 10 mL per dispense.

• Disposable pipette sample volumes between 1 mL and 10 mL per sample.

• Capable of supporting biomass analysist, Flex II, Raman Spectroscopy, Vi-Cell Blu.

1 Example of Stocked Materials ITEM Description Part # 175mL, 12 pck reagent bottles 001-2G50 300 μL disposable tips, 10 racks 001-2G72 10 mL disposable tips, 5 racks 001-2G78 reagent bottle, 1L- pack of 12 irradiated 001-2G51 mammalian vessels, pack of 6 001-5G21 24 way bioreactor tube kit for 250/24

(irradiated)-, 12/pack 001-2G48

• Supports automatic clean-in-place (CIP).

• Fully automated feedback control based on Flex II data.

• Maintains sterility during a 30-day culture process.

• Supports high density cell culture (> 50 million at a minimum).

• Provides real-time and ongoing liquid level control.

• Able to bleed and maintain desired cell density.

• Integrated pump design is positive displacement pumping.

• Includes 8 ea 1 L and 8 ea 175 mL media positions, all 1 L positions may be stirred at 0 -

500 rpm.

• Includes 10 pipette tip rack positions for automated pipetting.

• Includes 8 chilled samples positions (4-8 C or ambient).

• Works with the following sample tube sizes: 24 ea 2 mL, 24 ea 15 mL, 12 ea 20 mL, 6 ea 50 mL, as well as deep well V-bottom plates.

• Requires CO2, N2, O2, and Compresses Air at 25 psi; optional addition 75 psi

Compressed air requirement.

• Possesses exhaust gas analysis.

• Capable of online pCO2 measurement.

• SCADA capable – Lucullus integration with current Program’s configuration.