Xuri™ Cell Expansion System W25
Contents
1. Cell Expansion System W25 is not a medical device nor CE marked and should not be used in diagnostic processes GE imagination at work and GE monogram are trademarks of General Electric Company Cellbag UNICORN WAVE WAVE Bioreactor and Xuri are trademarks of GE Healthcare companies DeltaV is a trademark of the Emerson Process Management group of companies Windows and Windows XP are registered trademarks of Microsoft Corporation Cellbag bioreactors with integrated optical sensors are sold under a sublicense from Sartorius Stedim Biotech under US patent numbers 6 673 532 7 041 493 and or its foreign equivalents 2013 General Electric Company All rights reserved First published Oct 2013 All goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them A copy of these terms and conditions is available on request Contact your local GE Healthcare representative for the most current information GE Healthcare Bio Sciences AB Bj rkgatan 30 751 84 Uppsala Sweden GE Healthcare Europe GmbH Munzinger Strasse 5 D 79111 Freiburg Germany GE Healthcare Bio Sciences Corp 800 Centennial Avenue P O Box 1327 Piscataway NJ 08855 1327 USA GE Healthcare Japan Corporation Sanken Bldg 3 25 1 Hyakunincho Shinjuku ku Tokyo 169 0073 Japan 29 0618 52 AB 10 20132. System Control Ex 7 pak y fy 5 Toe Hek aa i gt gt a i aA P _ wave a X Flow Scheme Chart x p Settings ll Can jum 00 Do off C z 02 21 9 Sampling 60 min Reading On on Cycle time 0s Cha 0 Gas flow 0 00 Limin Mf Rocking 20cm gt _acid Base J 0 E conre aciaseaen B Temp 31 8 a Setpoint 7 00 m Alert 100 1 90 2 m CEP 1A Tem Cellbag controller nr E A ke Media control So Cellbag 10 Cellbag Media control Wet dOAB A 5 wai Fed Batch j aN pee Feed 0 001 gt BS Harvest gt Fig 8 Monitoring and controlling all aspects of the culture is managed through the user friendly interface 29 0618 52 AB 5 Evaluation module In the Evaluation module content of the result files can be viewed analyzed and compiled as reports Reports can be customized saved and printed Automation of process parameters in pH and DO control UNICORN software automatically sets the desired proportional integral derivative PID control parameters based on Cellbag bioreactor size and gas flow set point The system also adapts the parameters during the run for optimization to reach a new set point or to maintain a current set point Alarms notifications and data logging UNICORN software gives easy access to all operations data and alarm conditions A dynamic graphical user interface shows the real time status of the run while data are automatically saved To minimize
3. in a regulated environment Documentation accompanying the system includes material certificates system specifications installation and operational qualification IQ OQ protocols and a detailed user manual UNICORN software is suitable for use in a manner that complies with 21 CFR Part 11 and Good Automated Manufacturing Practice GAMP 5 system overview and weight measurement The gas mixer delivers gas of a Xuri Cell Expansion System W25 components defined composition to the culture and is used for online Xuri Cell Expansion System W25 consists of a base unit control of culture pH and DO Liquid is delivered accurately a gas mixer and a pump which are all operated by the to the culture by the Xuri Cell Expansion W25 Pump Unit The UNICORN software installed on a client computer The pump has a flow range covering multiple applications from base unit is the main hardware unit which is used with additions of acid and base to fresh medium for perfusion culture a tray and a disposable Cellbag bioreactor The base unit An overview of the Xuri Cell Expansion System W25 is shown in has multiple functions including heating culture mixing Figure 2 The individual components are described in the text Lid Graphical user interface Xuri Cell Expansion W25 Pump Peristaltic pump oo k k E j feti ni Client computer Tray Xuri Cell Expansion System W25 Base Unit Xuri Cell Expansion W25 Installed w
4. 20 rpm Xuri Cellbag Control Unit Gas flow control range O to 1000 ml min Gas flow total accuracy process value to reference flow 10 ml min 3 of read value Fast fill flow 3 min CO control range 0 to 15 0 3 3 of read value when mixed only with air N CO measurement accuracy Total CO accuracy process value to reference CO content 0 7 3 of read value O control range 0 to 50 when mixed with N 21 to 50 when mixed with air 0 6 1 of read value within 0 to 50 when mixed only with air N O measurement accuracy Total O accuracy 1 2 1 of read value OH measurement range 4 5 to 85 OH measurement accuracy 0 05 for pH 6 75 to 7 25 0 1 for pH 6 5 to 7 5 PH control range 6 0 to 8 0 Total pH accuracy process value to reference pH 01 107 PH 6 5 10 7 25 0 15 for pH 6 5 to 7 5 DO measurement range 0 to 250 air saturation 5 air saturation excl atmospheric pressure variations DO measurement accuracy DO control range 0 to 100 air saturation 10 air saturation excl atmospheric pressure variations Total DO accuracy process value to reference DO Xuri Cell Expansion W25 Pump 100 ml to 144 l d 0 07 to 100 ml min Pump flow rate range 0 1 ml min 5 of read value after calibration Pump flow accuracy Accumulated pumped volume accuracy 10 of measured volume id 0 5 to 4 8 mm 1 50 to 3 16 wall thickness 1 6 m
5. GE Healthcare Life Sciences Data file 29 0618 52 AB UTI Xuri Cell Expansion System W25 has been specifically designed for cell therapy manufacturing applications This functionally closed system is based on the proven WAVE rocking technology which provides mixing and aeration to the culture resulting in high cell densities whilst minimizing the risk of contamination The system is enhanced by sensors to monitor your cell expansion and is operated via UNICORN control software eTM Xuri Cell Expansion System W25 offers the following benefits e Minimized risk of cell contamination e Reach high cell densities with confidence e Advanced control of cell expansion through process monitoring and remote operation e Suitability for use in a regulated environment The system delivers reliable and accurate performance across research process development and manufacturing environments xuri Cell Expansion System W25 is intended for a variety of cell culture applications such as expansion of primary T lymphocytes System benefits Minimized risk of cell contamination The Xuri Cell Expansion System W25 is a functionally closed system which minimizes the risk of contamination between different patient samples or with adventitious agents The cells are grown in a single use Cellbag bioreactor High cell densities and perfusion culture The system is designed for both batch and perfusion culture Perfusion culture in a singl
6. H sensors measurement preinstalled in Cellbag bioreactors of pHOPT type The sensor is connected to the Xuri Cellbag Control Unit via a fiber optic cable DO The DO level is measured with optical DO sensors measurement preinstalled in Cellbag bioreactors of DOOPT type The sensor is connected to the Xuri Cellbag Control Unit via a fiber optic cable Xuri Cell Expansion W25 Pump The Xuri Cell Expansion W25 Pump is a peristaltic unit incorporating two roller pumps for feed waste and pH control of the environment in the Cellbag bioreactor Tubing installation is easy and tubing sizes from 0 5 mm 1 50 to 4 8 mm 3 16 internal diameter can be used to support flow rates from 0 07 to 100 ml min Flow rate is regulated by feedback from the load cells and automatic adjustments of the pump speed Manual adjustment of the flow rate is also possible if required during process development Media handling and perfusion using calibrated pumps Calibration of pumps can be performed manually or automatically during an ongoing perfusion process Automatic calibration is possible for flow rates above 3 5 I d and is easily managed by entering the tubing diameter UNICORN software UNICORN system control software consists of four modules to ensure intuitive setup and operation Administration Method Editor System Control and Evaluation supported by a comprehensive help tool Administration module The Administration module administers a
7. UNICORN software e 21 CFR Part 11 system assessment in checklist format e Audit report and 21 CFR Part 11 conclusion on functionality by an external independent expert 6 29 0618 52 AB Networking capabilities UNICORN software operates in Windows XP and Windows 7 environments and the network ability allows real time control from a remote or local computer Communication is Ethernet based and each instrument is controlled by a dedicated instrument server One database can be connected to 32 systems and up to three instruments can be controlled simultaneously from one UNICORN client Results are saved locally in the base unit during the run and then stored on the database server Because results and instructions are saved locally on the embedded drives a run can continue even in the event of a network communication failure minimizing the risk of losing your sample UNICORN software can be integrated in a supervisory control and data acquisition SCADA system such as the Emerson DeltaV control system using the UNICORN OPC server System specifications System specifications are listed in Table 3 Table 3 Xuri Cell Expansion System W25 specifications General system specifications Control system Dimensions W x H x D Base Unit Tray 10 Tray 20 Tray 50 Lid 10 Lid 20 Lid 50 Cellbag Control Unit Pump Weight Base Unit Tray 10 Tray 20 Tray 50 Lid 10 Lid 20 Lid 50 Cellbag Control Unit Pump Power supply P
8. able temperature control Mixing and gas transfer The speed angle and motion of rocking are adjustable These parameters together with the cell culture volume affect the mixing and rate of gas transfer in the Cellbag bioreactor The speed parameter determines the number of rocking cycles per minute and the angle parameter relates to the tray s degree of tilting at the turning points The motion parameter determines the acceleration profile of the rocking motion The lowest motion parameter setting 15 gives an almost constant speed throughout the rocking cycle whereas the highest setting 100 gives a faster rocking speed in the middle of the cycle and slower at the turning points Fig 6 A lower percent setting will give a more aggressive mixing with higher gas transfer rates A higher setting will result in a smoother wave suitable for more delicate applications such as adherent cultivation on microcarriers 29 0618 52 AB 3 Rocking profile 15 10 Angle nA o uw 10 O 0 5 1 0 1 5 2 0 2 5 3 0 Time s 20 10 10 Angular velocity s O 20 ie 0 5 1 0 1 5 2 0 2 5 3 0 Time s m Rocking profile 100 Angle EE O 0 5 1 0 1 5 2 0 2 5 3 0 Time s Angular velocity s D gt w Oo O O O O O 0 5 1 0 15 2 0 25 3 0 Time s Fig 6 A user defined rocking motion can be selected in UNICORN system control software The wave can be aggressive or gentle which can
9. affect mixing and gas transfer Weight measurement Load cells located in the base unit provide accurate and continuous measurement of the weight of the culture The load cells communicate with the system control software for accurate medium handling and for tailored regulation of pH and temperature Weight measurement is also used for automatic calibration of the pump in perfusion cultures Adjustable feet enable equal weight distribution between the load cells and accommodate uneven surfaces making instrument setup easier 4 29 0618 52 AB Cellbag bioreactors Cellbag bioreactors are single use bags for the mixing of culture medium and cells during cultivation Fig 7 Cellbag bioreactors require no sterilization or cleaning steps The single use functionally closed bags provide a suitable environment for cell growth while minimizing the risk of cross contamination The bags are manufactured from multilayer laminated clear USP Class VI plastics and are easily connected to the full suite of Xuri cell expansion cell culture purification and fluid handling products The selection of Cellbag bioreactors is listed in Table 1 For more information about Cellbag bioreactors see Data file 28 9511 36 Optical DO sensor embedded in bag Air outlet filter Optional tubing Air inlet filter Inoculation harvest lines Optical pH sensor embedded in bag Cellbag rod Optional tubing Optional tu
10. bing Needleless sampling port Fig 7 Cellbag bioreactor showing fittings Table 1 Selection of Cellbag bioreactor sizes Cellbag bioreactor Working volume Cellbag 2 300 ml to 1 Cellbag 10 500 ml to 5 Cellbag 20 1to10 Cellbag 50 Dto 25 m All Cellbag bioreactor sizes are available with internal perfusion filter for perfusion cultures and or can be equipped with single use optical pH pDHOPT and DO DOOPT II sensors N Cellbag bioreactors with optical sensors require 300 ml minimal working volume Depending on application and configuration it might be possible to cultivate below the recommended minimum volume However it is highly recommended to stay above this volume for applications that require high agitation and pH and DO control The temperature pH and DO sensors need to be submerged in liquid throughout the complete rocking cycle to function correctly Data storage and communication Data and control parameters are stored on two independent mirrored solid state drives integrated in the base unit Thus once a culture has been started and data from the instrument modules have been collected the run can continue without the need for a network connection The use of two solid state drives enables culturing without losing any data even if only one drive is functional Ensuring that data is not lost and traceability is maintained is required in a regulated environment After a run data is stored i
11. e Cellbag bioreactor results in high cell density which is often needed for cell therapy purposes This means that an entire dose of cells for a patient can be obtained in one functionally closed bioreactor system without the need to open the vessels to change the cell culture medium This also eliminates the difficulties of combining culture vessels as is necessary with manual systems High cell density together with the small instrument footprint maximizes use of limited manufacturing space Cell expansion Cell Expansion system W25 Fig 1 Xuri Cell Expansion System W25 is designed for cell therapy manufacturing applications Advanced control with process monitoring and remote operation xuri Cell Expansion System W25 is equipped with sensors and automated controllers for key culture parameters rocking speed dissolved oxygen DO pH and perfusion rate which enable cell specific optimization of the cell expansion culture environment and production of high quality and high density cells Once a culture is underway data is logged and recorded in the base unit as well as in the software The system can be monitored and controlled remotely and it can send e mail alerts if user defined limits are exceeded These features provide the monitoring and tracking necessary in a regulated environment Designed for use in a regulated environment Xuri Cell Expansion System W25 is designed to meet the demands and standards required
12. ent from integrated load cells The ability to handle the bioreactor in a tilt position facilitates sampling and harvest Fig 3 The small footprint is also advantageous when space is limited A B Fig 3 A Xuri Cell Expansion System W25 in tilt position B The ergonomic design makes activities such as sampling and harvest convenient and easy Trays and lids Trays are available in three different sizes for culture volumes of up to 5 10 and 25 The trays attach easily to the base unit in the tilt position and a snap lock mechanism ensures the Cellbag bioreactors are correctly installed and can be quickly changed Fig 4 To protect light sensitive components of the culture medium and to prolong the life of the optical sensors lids are available for all tray sizes Fig 4 The tray has an easy lock mechanism for convenient and proper attachment of Cellbag bioreactors Temperature control Reliable efficient and evenly distributed heating is provided by the tray heater plate The temperature measurement is managed by sensors integrated in the rocker base unit Fig 5 To minimize the risk of overheating heating Is only enabled when the base unit is in motion For accurate stable and fast temperature control the heater power output is automatically adjusted based on the Cellbag bioreactor size and the media volume Temperature sensors Fig 5 Integrated temperature sensors for convenient handling and reli
13. ith Rocker temperature sensors Cellbag Control Unit CBCU UNICORN software scale embedded controller Gas flow mix controller and dual hard drives pH and DO sensors System setup and integration of subunits Xuri Cell Expansion System W25 Base Unit Xuri Cell Expansion W25 Pump e Acid base flow e Rocking e Feed harvest flow ae e Weight a a e Media addition measurement e Temperature UNICORN software measurement Xuri Cell Expansion W25 Cellbag Control Unit CBCU e Gas flow mix Controller with dual hard drives e pH measurement e DO measurement e Administration e System control e Method editor e Evaluation LAN OPC ery eee wees I O f F UNICORN SCADA database j not included SS e a O a UNICORN software E mail At home or within notifications enterprise network Fig 2 Xuri Cell Expansion System W25 overview The System Control module on the client computer is used to start and monitor the cultivation process One UNICORN client can control up to three Xuri Cell Expansion W25 systems simultaneously SCADA supervisory control and data acquisition OPC open platform communications LAN local area network 2 29 0618 52 AB Xuri Cell Expansion W25 Base Unit The base unit is the main hardware unit providing mixing of the culture through the rocking of the attached tray and Cellbag bioreactor reliable temperature measurement from integrated sensors and accurate weight measurem
14. ll functions of the UNICORN software such as user and e mail setup access control for groups set up of network users defining and editing system properties database management and logging of usage and activity Method Editor module Instructions to control a bioreactor run are defined in a method The Method Editor module is used to create edit save and work with methods Changes can be made to an existing method to simplify the editing process To maximize reproducibility individual changes can be saved for later use on systems having the same instrument and component configuration System Control module The System Control module is used to connect the system and to start view and control a run Fig 8 It is also possible to connect to other Xuri Cell Expansion Systems W25 when scaling up Default parameter values for an instrument can be viewed and edited in the System Settings dialog before a run is started or during a run using manual instructions The Process Picture pane enables manual interaction with the system and displays the status of the run parameters Data is shown in the process picture but can also be viewed as curves in the Charts tab and as numerical values in the Run Data pane Curves and information about the run are saved in a database which can be opened in the Evaluation module The default view shows the most commonly used curves The display color and style of curves can be customized
15. m 1 16 Supported tubing dimensions 29 0618 52 AB 7 Ordering information Product Xuri Cell Expansion System W25 Base Unit Xuri Cell Expansion System W25 Cellbag Control Unit pH Xuri Cell Expansion System W25 Cellbag Control Unit Full Xuri Cell Expansion System W25 Pump Tray 10 Tray 20 Tray 50 Lid 10 Lid 20 Lid 50 Filter heater Bag sensor adapter 2 5 m assembly UNICORN 6 3 2 Workstation Package software and license UNICORN 6 3 Remote license UNICORN 6 3 Dry license Related literature Disposable Cellbag bioreactors for Description Base unit Gas flow mix and pH Gas flow mix pH and DO For up to 5 culture For up to 10 culture For up to 25 culture To fit Tray 10 To fit Tray 20 To fit Tray 50 Fiber cable for pH and DO control WAVE Bioreactor systems Data file UNICORN 6 3 Manual package UNICORN 6 control software Data file UNICORN 6 3 Validation support file For local office contact information visit www gelifesciences com contact www gelifesciences com xuri GE Healthcare UK Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA UK Code number 29 0645 68 29 0646 00 29 0646 02 29 0645 71 29 0652 31 29 0652 52 29 0444 74 29 0652 31 29 0652 35 29 0652 gt 5 29 0652 52 28 9841 89 29 0469 18 29 0203 51 29 0203 55 28 9511 36 29 0234 67 28 9573 46 11 0029 94 imagination at work Xuri
16. n a UNICORN database on an external computer For integration into a manufacturing operation the base unit contains software that enables direct communication with the system via an open platform communication OPC link Xuri Cellbag Control Unit The Xuri Cellbag Control Unit provides gas to the culture and monitors pH and DO The control unit contains a controller for mass flow sensors for gas pressure as well as O and CO concentrations and transmitters for pH and DO Table 1 Three Xuri Cellbag Control Unit configurations are available e CO 0 pH and DO e CO 0 and pH e CO O and DO The most suitable configuration will depend on the specific application Table 2 Xuri Cellbag Control Unit overview Feature CO O air mix controller Description Depending on the configuration air is mixed with CO and or O according to the set points Nitrogen may be used instead of air for maintaining a low oxygen environment for near anaerobic applications Gas flow controller The gas mix flow is measured and controlled by a mass flow controller MFC A correct volumetric flow is achieved by compensation for CO concentration Quick filling of gas into the Cellbag bioreactor enabled by the fast fill function Significantly reduces start up time An alarm will inform the user if pressure sensors detect under or overpressure at the gas inlets or within the Cellbag bioreactor pH The pH is measured with optical p
17. ower consumption Enclosure protective class Gas supply External air supply 1 0 to 1 5 bar External CO supply 1 0 to 1 5 bar External O supply 1 0 to 1 5 bar Environmental aspects Operating ambient temperature range Operating humidity range UNICORN 6 3 or later version 404 x 560 x 205 mm 475 x 430 x 60 mm 740 x 480 x 70 mm 800 x 610 x 70 mm 475 x 430 x 230 mm 740 x 480 x 245 mm 800 x 610 x 260 mm 276 x 360 x 117 mm 275 x 280x115 mm 24 kg 4 5 kg 7 3 kg 9 5kg 1 7 kg 3 3 kg 3 9 kg 4 8 kg 3 8 kg 100 to 240 V 50 to 60 Hz 1500 VA IP Normal capacity Fast fill capacity 1 3 l min 3 5 l min 0 2 I min 0 5 I min 0 7 I min 1 7 l min 15 Ci032 C 20 to 80 noncondensing Xuri Cell Expansion System W25 Base Unit Rocking speed control range Rocking angle control range Rocking motion control range Media weight control range Scale absolute accuracy Temperature sensor Temperature measurement range Temperature control range Temperature control accuracy incl measurement error 2 to 40 rom 2 to 12 15 to 100 0 5 to 25 kg 0 050 kg 1 of load kg Pt100 Class A 2 CIO 50 C 20 C or ambient temperature 5 C to 40 C 205 C 1 When cultivating in a 50 Cellbag bioreactor at maximum working volume of 25 rocking speed and angle multiplied should not exceed 240 rpm degrees For example if the rocking angle is set to 12 degrees the rocking speed should not be set higher than
18. the risk of losing your sample UNICORN software can configure the system to trigger an alarm when certain conditions are met Individual deviation alarms can be set for all essential parameters heating gas flow CO pH and DO Alarm sensitivity and delay is defined by the user If an alarm condition is triggered the source is highlighted in the graphical user interface A dialog displays information about the alarm such as date and time of occurrence as well as a help text describing the cause and solution The system can be configured to send e mail notifications of alarms and errors to trigger your prompt response Regulatory readiness The Xuri Cell Expansion System W25 is suitable for biomanufacturing of regulated products under various Quality Management Systems The use of UNICORN software in a 21 CFR Part 11 and GAMP 5 compliant manner enables use of the system in a regulated environment Individual user access permissions can be set and individual users are password protected Active processes can be locked to enable unattended operations without the risk of unauthorized interference All records are stored in a single unalterable database including results and extended run documentation Additional validation support includes comprehensive documentation on control system validation as well as IQ OQ services Available validation support documentation includes e Detailed description of the development model used for
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