Product Datasheet

Benefits

- Intuitive control system employing step editor software - Easy set up and installation of manifolds - Good selection of single-use sensors

Product Information

The Allegro CS1000 and CS4500 single-use tangential flow (SUTFF) systems offer all the control and instrumentation for running fully automated UF | DF processes from 500 to 2000 L batches. The approach to design offers systems that are compact, ensure low feed | retentate volumes, and have the flexibility to run cassette surface areas from 0.5 to 10 m2.

Allegro™ Fully Automated, Single-Use Tangential Flow Filtration SystemsFor control, flexibility and ease of use in manufacturing

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System ConceptAllegro SUTFF systems offer a combination of hardware, control systems and SU assemblies designed to work per-fectly together. Clever system design ensures ease of use in running fully automated TFF process sequences, with complete single-use assemblies, incorporating all of the critical sensor and instrumentation technologies.

Flexibility is a key requirement for single-use system design. These systems offer the end user a choice of single-use sensors for feed, retentate and permeate manifolds. A range of 2D and 3D bags are available for retentate, product re-covery and buffer | WFI. Weigh scales and mixer technolo-gies can also be offered with these systems, to suit individu-al process requirements.

A review of specific process needs with our engineering team will ensure a solution is offered to meet exactly all of the process requirements. This might be achieved with one of our standard platform designs for SUTFF, along with standard totes and mixers. Or it might lead to the creation of a custom design. The custom designs will still retain the core components that we have vali dated for use in SUTFF processes. But we have the flexibility to integrate our sys-tems with other plant equipment, plant control systems and offer systems designed for running other TFF formats such as hollow fibers.

The use of validated components for running SUTFF processes is extremely important for success in design and ultimate system performance of our systems. Continuity of these components is maintained throughout our offering in SUTFF processing.

The Allegro SUTFF systems facilitate the automated processing of 500 L to 2000 L batch volumes of monoclonal antibodies, recombinant proteins, vaccines and anti-body-conjugate processes. The single-use sensors provide the means to monitor and control the process fully.

The system design gives full consideration to ease of use in system set up and processing, while ensuring use of com-ponents and instruments that can achieve the performance requirements for TFF processes.

Adopting SUTFF technologies can have many potential benefits in a process. Cost of Goods studies have shown significant savings in capital, materials, labor and facility op-erating costs when comparing SUTFF to regular processing with stainless steel TFF systems. A more flexible approach in manufacturing can lead to increased productivity and bet-ter resource allocation.

Control SystemThe automation concept is based on the Process Step Editor (PPSE), which allows the user to configure automat-ed process sequences (phases) in a very simple and user friendly way. This is a very intuitive control system ideal for use in the Allegro SUTFF systems, with a phase editor that allows easy generation and configuration of end user specific processes. The software complies with CFR21Part11.

Main screen with indication of all process signals as well as system | com-ponent status

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The user can select the transition points which move the process from one step to the next. This can be done by selection of one or several process parameters (with an “and” or “or” logic) such as conductivity, retentate volume, permeate volume, biocontainer weight.

Further flexibility is added as the system allows the configu-ration and use of loop and jump functions thus making selective step repetitions feasible.

Upon operator’s selection batch reports will be generated automatically at the end of a batch for each single step. The content of the batch report is predefined.

CS1000 cassette holders, with manual torque, for 0.5 to 2.5m2 membrane area

Key System Features - Interactive P&ID based user interface with dynamic flow path - Flow, TMP and bag weight controller - Phase based automation (one phase comprising up to 30 freely definable steps) - Easy to use phase editor - Full security access to configuration - Real-time trending - Graphic data analysis using the Analytical Tool - Data and event logging - Batch report generator (one page per step) - User administration - Audit Trail

Technical DataSystems Technical Specification CS1000

Membrane area 0.5 – 2.5 m2 (dictated by specific process crossflow versus recirculation pump capacity)

Feed and retentate tubing ID

½ in. (12.7 mm)

Permeate and productinlet | diafiltration bufferTube ID

½ in. (12.7 mm)

Recirculation pump Quattroflow™ 1200SU,4-Piston Diaphragm Pump20 to 1000 L/hr

Fed batch | Buffer pump

Ismatec Flowmaster™ FMT300 Peristaltic pump, ISM Drive6 – 600 L/hr with 12.7 mm element

Recirculation biocontainer

20 L, 50 L, 100 L tote or 50 L, 200 L mixer

Filter type Sartorius Sartocon® and Sartocube®, or equivalent

Over pressure protection

Yes

Maximum pressure 4 barg for reinforced manifold sections1 barg for permeate and medium pressure manifold sections0 barg for biocontainers

Volume in feed andretentate lines

650 mL

Non recoverable volume <100 mL

Operating temperature range 4 – 40°C

System frame and cabinet materials of construction

304 stainless steel

Dimensions system with retentate 20 L tray(length × depth × height)

1800 × 800 × 1600 mm (nominal)

Dimensions system withretentate 100 L tote(length × depth × height)

1800 × 800 × 1955 mm (nominal)

Weight of empty system 350 Kg

Power 230 V, 1-phase 50 Hz; 120 V,1-phase 60 Hz

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Systems Technical Specification CS4500

¾ in. manifold assembly

1 in. manifold assembly

Membrane area 3.0 – 10 m2 (dictated by specific process crossflow versus recirculation pump capacity)

Feed and retentate tubing ID

¾ in. (19.05 mm) 1 in. (25.4 mm)

Permeate and product inlet | diafiltration buffertube ID

½ in. (12.7 mm) ½ in. (12.7 mm)

Recirculation pump

Quattroflow-5050SU 4-Piston 480 – 2000 L/h with3-degree shaft480 – 2940 L/h with6-degree shaft

Sanitary Diaphragm Pump 600 – 4500 L/h with 6-degree Pump Model

Fed batch | Buffer pump

Quattroflow-1200SU, 4-Piston Diaphragm Pump 20 to 1000 L/hr

Recirculation biocontainer

200 L tote or mixer 500 L tote or mixer

Filter type Sartorius Sartocon® and Sartocube®, or equivalent

Over pressure protection

Yes

Maximum pressure

4 barg for manifold sections 0 barg for biocontainers

4 barg for manifold sections 0 barg for bio containers

Volume in feed and retentate lines

1.9 L 2.5 L

Non recoverable volume

<100 mL <100 mL

Operating tem-perature range

4 – 40°C

The CS4500 has been designed to run both ¾ in. and 1 in. manifolds, using the same base hardware. The clamps on the pinch valves are specific to one size of tubing and these are easily changed out.

System frame and cabinet materials of construction

304 stainless steel

Dimensions process skid (length × depth × height)

1920 × 1000 × 1718 mm (nominal)

Dimensions retentate trolley with 200 L tote(length × depth × height)

747 × 975 × 1545 mm (nominal)

Dimensions retentate trolley with 500 L tote(length × depth × height)

955 × 1300 × 1600 mm (nominal)

Weight of empty system

420 Kg

Power 400 V, 3-phase 50 Hz

CS4500 cassette holder: central distribution plate, with or without auto torque. 3.0 to 10 m2 membrane area: regular T-series cassettes

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Component Specifications

CS1000 CS4500 ¾ in. manifold assembly

CS4500 1 in. manifold assembly

Recirculation pump Flow range 20 to 1000 L/hour 480 – 2000 L/hr with 3-degree shaft 480 – 2940 L/h with 6-degree shaft

600 – 4500 L/hr with 6-degree shaft

Fed batch | Buffer pump 6 – 600 L/hr with 12.7 mm element

20 to 700 L/hr 20 to 700 L/hr

Pneumatic pinch valves For use with ½ in. tubing For use with 1 in. ID or ¾ in. ID tubing (feed and retentate)For use with ½ in. ID tubing (permeate and product inlet | diafiltration buffer)

Control valve Single-Use diaphragm valve body with positioner

Single-use diaphragm valve body with positioner

Recovery valve Single-use diaphragm valve body Single-use diaphragm valve body

Retentate flow measurement

20 – 1200 L/hr ± 5% Configurable for a defined flow range (5% accuracy full scale)

Permeate flow measurement

20 – 1200 L/hr ± 5%

Pressure measurement

-0.48 – 5.2 bar; ± 2% from 0 – 0.41 bar; ± 3% from 0.41 – 2.07 bar; ± 5% from 2.07 – 4.14 bar

Temperature measurement

0 – 70 ºC 2 – 50 ºC 2 – 50 ºC

Conductivity High range 10 – 200 mS/cm Low range 0 – 100 μS/cm)

Retentate: 0.0 to 150.0 mS/cmPermeate: 0.0 to 100.0 μS/cm and 0.1 to 150.0 mS/cm (reading switches between the two ranges)± 2% of measured value ± 0.4 μS/cm (dependent of process and ambient temperature being equal).

UV 0 – 2 AU ± 0.1 AU 0 – 3 AU ± 0.5% 0 – 3 AU ± 0.5%

pH n/a 0 – 12 pH units 0 – 12 pH units

Level sensor n/a Presence | Absence liquid on the product inlet line

Air flow n/a 0 – 12500 sccm ± 1% 0 – 12500 sccm ± 1%

Mass measurement 0 – 150 kg± 20 g readability

Appropriate size load cell will be defined for each process

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Single-Use Manifolds - Are assembled in a class 10000 clean room to ISO stan-dards 9001:2008 and using validated assembly methods - Have components that are tested for biocompatibility and certified to USP<88> - Have components that are certified TSE/BSA free - Are manufactures according to a validated assembly process - Are supplied double bagged and irradiated at a minimum dose of 25 KGy - Extractables data reports are available on request

Product contact materials for Allegro CS1000 and CS4500 SUTFF Systems

Process wetted components

Materials of construction

Tubing Platinum cured silicone, reinforced in high pressure sections

Product recirculation pump CS1000 and CS4500 Diafiltration | fed batch pump CS4500

Machined polypropylene head, EPDM valves and O-rings, Santoprene™ diaphragmMolded polyethylene head, polypropylene ports, EPDM valves and O-rings, Santoprene diaphragm

Connectors and fittings Polypropylene

Single sensors: - Pressure, UV - Temperature

- Flow - Conductivity

- Polysulfone - Polysulfone with stainless sensor and silicon ring - PVDF with ruby bearing - Polysulfone with gold electrode

Multi sensor cell:temperature | conductivity | pH | UV

PPSU (electrodes: SS 316 L, gaskets:EPDM, UV window: quartz)

Sanitary fittings Polypropylene, gaskets silicone

TC gaskets Silicone

Diaphragm valves Body polypropylene, diaphragm TPE

Biocontainers LDPE

Distribution plate Polypropylene

Quality StandardsA stringent approach to quality of purchased and manufactured components is maintained. The system hardware is designed and built to well recognized industry standards, including but not limited to: - Good automated manufacturing practice (GAMP)

current version - Code of Federal Regulations 21 – Good manufacturing practice for finished pharmaceuticals. - 2004/108/EC - Software complies with CFR21Part11 for electronic records, signature and audit trail - Code of Federal Regulations 21 – Good manufacturing practice for finished pharmaceuticals. - The rules governing medicinal products in the European Community, Volume IV, and Good Manufacturing practice for medicinal products, Annex 11, computerized systems.

A quality management system according to DIN EN ISO9001: 2008, EN 729 has been implemented. This quality management system is certified by an independent third party.

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Summary

The combination of single use technologies and automation provides many benefits in bioprocessing. Fully automated SUTFF systems make UF | DF a straightforward process with full control over the key parameters.

The Allegro SUTFF systems provide control, flexibility and enable processing to be carried out under optimum conditions using fully automated process sequences

Full automation Enables precise and consistent operation and control of key parametersMinimizes operator contact

Fully disposable flowpaths

Easy system set upReduces cleaning time, improves productivity and provides cost savings in manufacturing

Single-use sensors Monitoring and control of key TFF process parametersEnables automated control of processing to optimum conditions

Process step editor software

Flexibility to create recipes to suit individual processesMonitors all process variables and provides data logging and batch reports

Sales and ServiceContactsFor further contacts, visitwww.sartorius.com

Specifications subject to change without notice.Copyright Sartorius Stedim Biotech GmbH.DIR: 2578666-000-00Status: 04 | 2020

GermanySartorius Stedim Biotech GmbH August-Spindler-Strasse 11 37079 GoettingenPhone +49 551 308 0

USASartorius Stedim North America Inc. 565 Johnson Avenue Bohemia, NY 11716Toll-Free +1 800 368 7178