XCell ATF Series User manual

XCellTM ATF System
With C410:V3 Controller
USER GUIDE
XCell™
ATF4
XCel
l™ATF6
XCell
™ ATF10

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their respective owners.
Revision History
C410:V3 User Guide
XCellTM ATF System with C410 Controller, Version v3
Revision 5, November 2019

Contents
1. Description of XCellTM ATF System and Process......................................................................1
1.1 XCellTM ATF System Pump Cycle ....................................................................................2
1.2 XCellTM ATF System Control Scope and Objectives:.......................................................4
1.3 XCellTM ATF Pump Housing and Controller Pairings ......................................................4
1.4 XCellTM System Interconnectivity Drawing ....................................................................5
2. Utility Requirements.............................................................................................................6
3. Size and Weight....................................................................................................................7
4. XCell™ ATF Pump Housing Assemblies...................................................................................8
5. C410:V3 Controller Layout ..................................................................................................17
5.1 General Layout.............................................................................................................17
5.1.1 Filtration Assembly ............................................................................................18
5.2Primary Pneumatic Services.........................................................................................19
5.3 Primary Electric Services..............................................................................................21
5.4 Signal............................................................................................................................21
5.5 C410:V3 Ethernet set-up and Connectivity .................................................................21
6. C410:V3 Controller Process and Control ..............................................................................22
6.1 Interface and screens...................................................................................................22
6.2 Control Overview .........................................................................................................45
6.3 Start-up ........................................................................................................................46
6.4 Examples ......................................................................................................................48
7. Hollow Fiber Module and Diaphragm Replacement .............................................................50
7.1 Separating the Filtration Assembly from the bioreactor:............................................50
7.2 HFM removal: ..............................................................................................................50
7.3 HFM insertion: .............................................................................................................51
7.4 Screen Module replacement: ......................................................................................52
7.5 Diaphragm replacement: .............................................................................................52
7.6 Assembly ......................................................................................................................53
7.7 Use ...............................................................................................................................53
8. Sterilization........................................................................................................................53
8.1 Preparation of Filtration Assembly for autoclaving.....................................................53

8.2 Autoclave Cycle............................................................................................................55
8.3 Sterilization of Filtrate / Harvest line..........................................................................56
9. Connection to Bioreactor ....................................................................................................56
9.1 Hard Connection ..........................................................................................................57
10. Maintenance ......................................................................................................................57
10.1 Diaphragm....................................................................................................................57
10.2 Pump Air Inlet Filter.....................................................................................................57
10.3 “O” Rings, gaskets and Quick Connects.......................................................................57
10.4 Controller Maintenance...............................................................................................58
Appendix 1: XCellTM Cycle Time vs. Flow Rate..............................................................................59
Appendix 2: User Access.............................................................................................................60
Appendix 3: Declaration of Conformity.......................................................................................71
Appendix 4 Pressure Relief.........................................................................................................74
Appendix 5: Profinet Communication .........................................................................................75
Appendix 6: Spares List ..............................................................................................................81

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XCellTM ATF System with C410:V3 Controller
User Guide
1. Description of XCellTM ATF System and Process
The XCellTM ATF System provides an efficient means for fractionation of various mixtures. It may
include separation of large particles such as microcarriers (~ 200 microns in size) from a suspending
medium. It may include separation of mammalian cells (~ 10 microns in size) from culture medium;
or it may include separation of some molecules from other molecules or from a suspending solvent.
The focus in this manual will be on the use of the XCellTM ATF System and process for separation of
these constituents by filtration, based primarily on size.
The XCellTM ATF System is an alternating tangential flow filtration system consisting of the
following primary components (see also Figure 1):
•Controller: a dedicated controller used to control and monitor XCellTM ATF System
activity. It also provides the means for connecting to and controlling utility services.
•Filtration Assembly: a stainless steel assembly of two major elements, a filter housing
and a diaphragm pump:
-Filter Housing:steel housing containing the filtration element, either a hollow fiber
module (HFM) or screen module (SM).
-Diaphragm Pump:steel spherical housing in which a diaphragm membrane is moved up
and down by pressurized air or vacuum, creating alternating flow.
The Filtration Assembly includes the following components for each process application:
-Connection Assembly:tubing assembly connecting the Filtration Assembly to a bioreactor
or process vessel
-Bioreactor Adaptor: adaptor between the Connection Assembly and bioreactor port.
Typical ports/connectors/adaptors for stainless steel bioreactors include an Ingold-type
port or, if a single use bioreactor (SUB), then, a disposable aseptic connector (DAC) or
equivalent.
A typical configuration of the XCellTM ATF System is shown in Figure 1. The Filter Housing
accepts either a HFM, with pore sizes from 30kD to ~0.5 micron, or a SM for fractionation of
larger particles, >70 microns. The separating element, the HFM or SM, is positioned
between a process vessel or a bioreactor at one end and the Diaphragm Pump at the other
end. The vessel serves as a storage container for the content to be filtered. The Diaphragm
Pump provides the means for generating alternating tangential flow (ATF), back and forth,
between the vessel and pump, through the hollow fibers of the HFM or through the SM. The
ATF process provides the means for generating rapid, low shear, tangential flow. A filtrate
pump as shown in Figure 1 is used for controlled removal of a filtered stream. The unfiltered
material remains in the system. The XCellTM ATF System provides the means for confining
the process. The entire process is enclosed. Only a single connection is required between
the XCellTM ATF System and the vessel. As shown in Figure 1, that connection can be either
through a head plate of the vessel or through a side or bottom port. Placing the Filtration
Assembly next to the vessel requires only a short tubing to complete the connection
between the two. That connection can be hard piped or soft piped. Either one may be used
to make a sterile connection between vessel and the Filtration Assembly, as will be
discussed further on.

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XCellTM ATF System with C410:V3 Controller
User Guide
Figure 1. Filtration Assembly connection to C410:V3 Controller and a bioreactor side port
1.1 XCellTM ATF System Pump Cycle
The Diaphragm Pump is the heart of the ATF process. It produces an alternating flow
through the HFM (lumen side) or SM. The XCellTM ATF System provides a pulsating,
reversible, flow of liquid, back and forth, between the process vessel and the Diaphragm
Pump. The following is a description of that process:
The Diaphragm Pump is partitioned into two chambers with a flexible diaphragm, Figure
2. One of the pump chambers, the Pump Liquid (PL) chamber is connected to the Filter
Housing, which, in turn, is connected to the process vessel. Therefore, any flow between
the Diaphragm Pump and process vessel will be through the filtration device. The
second pump chamber, the Pump Air (PA) chamber, is connected to the pump flow
control system. Typically, controlled addition of compressed air into the PA chamber
increases the pressure in the chamber relative to the process vessel, forcing the flexible
diaphragm partitioning the two chambers to move into the PL chamber and towards the
vessel. Liquid in the PL chamber is forced through the filter to the process vessel. The
flow through the HFM (lumen side) generates tangential flow in one direction. This
pumping phase (or cycle) is called the Pressure Cycle. Inversely, with a pressurized
process vessel relative to PA or PL, or with an external vacuum supply, liquid will flow in
the reverse direction, from process vessel, through the HFM (lumen side), to the PL
chamber, generating tangential flow in the other direction. This pumping phase (or
cycle) is called the Exhaust Cycle. These alternating pump cycles are then repeated
continuously. See also Figure 2.

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XCellTM ATF System with C410:V3 Controller
User Guide
Figure 2. XCellTM ATF System Pump Cycles
Note on the Exhaust Cycle:
WARNING Glass bioreactors
or single-use bioreactors (SUBs), unless otherwise specified by the manufacturer of
the vessel, should not be pressurized. Such vessels can explode if pressurized.
Therefore, to increase the pressure in the vessel relative to the Diaphragm Pump, a vacuum
service is required. The PA chamber can then be alternately pressurized and evacuated to
produce ATF flow while maintaining the process vessel at atmospheric pressure.
On the other hand, when using a vessel that can be pressurized, vessel pressure can be used
to drive the liquid from the vessel to the PL chamber. When vessel pressure is limited, it
may be supplemented with vacuum. In either of the above schemes, one is driving the liquid
from the vessel to the Diaphragm Pump by increasing the pressure in the vessel relative to
the Diaphragm Pump.
When using a glass vessel or SUB, be sure to maintain an unrestricted vent from
the vessel. In the case a diaphragm fails, the air flow into the Diaphragm Pump will
proceed through the HFM or SM into the vessel. A free exhaust from the vessel will
minimize the buildup of pressure in the vessel.

4
XCellTM ATF System with C410:V3 Controller
User Guide
1.2 XCellTM ATF System Control Scope and Objectives:
The C40:V3 controller provides the process control functionality of the XCellTM ATF4,
ATF6, and ATF10 Systems. The C410:V3 controller is designed to:
1. Control ATF flow rates in both pressure and exhaust phases
2. Provide a user interface capability for XCellTM ATF System control and monitoring
3. Set-up and select operation parameters
4. Display real-time process data
5. Alarm for error conditions
6. Provide “batch control” and user hierarchy
7. Have PLC software upgrades in the field by replacing memory modules
8. Have two major components, an Electronics Box (E-Box) and a Pneumatics Box (P-
Box)
9. Allow the E-Box to operate an XCellTM ATF4, ATF6, or ATF10 System using specific
software and modules.
10. Allow the P-Box hardware and process parameters to be specific to the size of the
particular XCellTM ATF System being controlled.
1.3 XCellTM ATF Pump Housing and Controller Pairings
XCellTM ATF Pump
Housing
XCellTM Controller
Description
XCellTM ATF4
Stainless Steel
C410:4V3
C410:V3 C410 controller for XCellTM ATF4
system with air tubing.
C410:4V3-GMP
C410:V3 C410 controller for XCellTM ATF4
system with air tubing and standard GMP
documentation and FAT.
C410:4V4B-GMP
Profibus configured C410-V4B controller with
power separation for XCellTM ATF4 system with
air tubing, standard GMP documents and FAT.
XCellTM ATF6
Stainless Steel and
Single-use
C410:6V3
C410:V3 C410 controller for XCellTM ATF6
system with air tubing.
C410:6V3-GMP
C410:V3 C410 controller for XCellTM ATF6
system with air tubing, standard GMP
documents and FAT.
C410:6V4B-GMP
Profibus configured C410-V4B controller with
power separation for XCellTM ATF4 system with
air tubing, standard GMP documents and FAT.
XCellTM ATF10
Stainless Steel and
Single-use
C410:10V3
C410:V3 C410 controller for XCellTM ATF6
system with air tubing.
C410:10V3-GMP
C410:V3 C410 controller for XCellTM ATF10
system with air tubing, standard GMP
documents and FAT.
C410:10V4B-GMP
Profibus configured C410-V4B controller with
power separation for XCellTM ATF10 system
with air tubing and standard GMP
documentation and FAT.

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XCellTM ATF System with C410:V3 Controller
User Guide
1.4 XCellTM System Interconnectivity Drawing
Figure 3. C410:V3 controller with XCellTM ATF10 stainless steel pump housing and pressure
relief valve

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XCellTM ATF System with C410:V3 Controller
User Guide
2. Utility Requirements
UTILITY
REQUIREMENT
COMMENTS
PRIMARY
COMPRESSED AIR
Maximum 90 psi /
6.1 bar
Oil free, dry, filtered gas, i.e., medical grade
air.
SECONDARY
PRESSURE
Typically: 35 psi /
2.4bar,
Working, regulated pressure
VACUUM SERVICE
~20” / 508 mm. Hg at
maximum flow
use a service capable of sustaining ~20”Hg
at full flow
EXHAUST
Untreated discharge or user specified
ELECTRICAL
100-240V AC, 50/60Hz
ENVIRONMENT:
0-50°C ; 0 – 80 % RH
Temperature; Relative Humidity
STEAM (SIP)
~30lbs/hr.
Applicable to a steamable connection
between Filtration Assembly and vessel.
CONDENSATE DRAIN
Condensate drain adequate with SIP
requirements

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XCellTM ATF System with C410:V3 Controller
User Guide
3. Size and Weight
The size of a Filtration Assembly may vary slightly based on XCellTM ATF system
configuration and accessories. The C410:V3 controller dimensions are fixed.
COMPONENT
DIMENSIONS
COMMENTS
H
W
D
C410:V3
Controller
inches
PNEUMATIC BOX
17
15
8
Includes all plugs and connectors.
ELECTRIC BOX
24
20
9
Includes all plugs and connectors.
Filtration
Assembly
Fully assembled system
XCell™ ATF 4
System
24 6 6x10
Indicated dimensions are estimates for the
Filtration Assembly, as the connection to the
bioreactor, the connections to the controller
and to accessories can affect height and
effective area.
XCell™ ATF 4MC
System
44 10 8x12
XCell™ ATF 6
System
44 10 8x12
XCell™ ATF 10lgcy
System
44 14 14x20
XCell™ ATF 10
System
44 14 14x20
XCell™ ATF 6
Single-use Device
38” 12” 10”
XCell™ ATF 10
Single-use Device
38” 14” 18”
C410:V3 Controller
Estimated WEIGHT (Kg)
COMMENTS
PNEUMATIC BOX ~13
Weight of the P-Box will vary
depending on the particular ATF
System it is configured to control.
ELECTRIC BOX
~23
Filtration Assembly
XCell™ ATF 4 System ~6
Weight does not include the weight of
any liquid, filter or connection
between the Filtration Assembly and
the vessel
XCell™ ATF 4MC System ~14
XCell™ ATF 6 System ~14
XCell™ ATF 10lgcy
System
~30
XCell™ ATF 10 System ~40
XCell™ ATF 6 Single-use
Device
~ 6
Does not include the weight of liquid
and A2B connectors
XCell™ ATF 10 Single-use
Device
~ 5
Does not include the weight of liquid
and A2B connectors

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XCellTM ATF System with C410:V3 Controller
User Guide
4. XCell™ ATF Pump Housing Assemblies
The Filtration Assembly of XCell™ ATF pump housing is shown in Figure 3. Certain parts may
vary, depending on requirements and specifications. Optional components for the XCell™
ATF housing include bioreactor connection kits, pressure transducers, vacuum pump, and
options for sanitary diaphragm valves. All are available upon request.
Figure 4a. Exploded View of XCell™ ATF 10 System Filtration Assembly (P/N ATF10:PH-
GMP)

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XCellTM ATF System with C410:V3 Controller
User Guide
Table 4a. XCell™ ATF 10 Pump Housing Parts List
Note: C-CLAMP (Hemisphere) Items #20,21 should be torqued to 20-25 ft-lbs with 1"
wrench flats
See Appendix 7 for list of spares and accessories
ITEM
NO.
DESCRIPTION Material QTY.
1
ASME Clamp, Assembly, XCell™
316 SS
2
2
Pump Hemisphere Air Side,
SA479 316L SS
1
3
Lifting Handle, Assembly, XCell™
316 SS
1
4
Pump Hemisphere Liquid Side,
316 SS
1
5
Filter Housing Assembly, XCell™
316 SS
1
6
Stand, Assembly, XCell™ ATF10
316 SS
1
7
Diaphragm, Pump, XCell™
50A P.C. Silicone
1
8
0.295" C/S x 6.835" ID x 7.425"
Silicone
2
9
90 Degree Elbow, 1.5TC
316 SS
1
10
Sanitary Gasket, 1 1/2" TC
EPDM
5
11
Clamp, Sanitary, 1 1/2" TC
304 SS
5
12
Sanitary Gasket, 3/4" TC
EPDM
4
13
Sanitary Gasket, 1/2" TC
EPDM
3
14
Clamp, Sanitary 1/2-3/4" TC
304 SS
7
15
Sanitary Cap 3/4"
316 SS
2
16
Sanitary Diaphragm Valve, 1/2"
316 SS
3
17
Window, Sanitary 1.5"TC
AISI Type 316LSS
2
18
Pressure Gauge, 1.5" TC, 30 psi
SS
1
19
45 deg Elbow, 3/4" TC
SS
1
20
C Clamp w/ Lock-B, Assembly,
316 SS
3
21
C Clamp w/ Lock-A, Assembly,
316 SS
3
22
Air Inlet Filter, 0.2 micron, 1/2"
PVDF
1
23
Instrument Tee, 1.5" x 2X 3/4"
316 SS
1
24
Reducer, XCell™ ATF10
SA479 316L SS
1
25
Spectrum F10 2 Micron PES
NA
1
26
3/8” Hex Bit Socket, 3/8” Drive
Alloy Steel
1

10
XCellTM ATF System with C410:V3 Controller
User Guide
Figure 4b. Exploded View of XCell™ ATF 10 Single-use Device with 0.2u PES Hollow Fiber
Filter

11
XCellTM ATF System with C410:V3 Controller
User Guide
Table 4b. XCell™ ATF 10 Single-use Device Components

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XCellTM ATF System with C410:V3 Controller
User Guide
Figure 4c. Exploded View of XCell™ ATF 6 System Filtration Assembly (P/N ATF6:PH-GMP)

13
XCellTM ATF System with C410:V3 Controller
User Guide
Table 4c. XCell™ ATF 6 Pump Housing Parts List

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XCellTM ATF System with C410:V3 Controller
User Guide
Figure 4d. Exploded View of XCell™ ATF 6 Single-use Device with 0.2u PES Hollow Fiber
Filter

15
XCellTM ATF System with C410:V3 Controller
User Guide
Table 4d. XCell™ ATF 6 Single-use Device Components
ITEM
NO.
ITEM DESCRIPTION QTY
1
Pump Hemisphere: Air Side: XCell suATF6
1
2
Diaphragm: Pump: ATF6
1
3
Pump Hemisphere: Liquid Side: XCell suATF6
1
4
Housing Tube: XCell suATF6
1
5
Reducer: XCell suATF6
1
6
3/4" TC: Pump Hemisphere: Liquid Side: XCell
suATF6
1
7
Spectrum F6 2 Micron PES Hollow Fiber Cartridge
1
8
Pump Lock Ring: XCell suATF6
1
9
Permeate Port: Housing: XCell suATF6
2
10
Sanitary Gasket: Silicone: 3/4" TC
1
11
413 O-Ring: Class VI: 70A Silicone
2
12
233 O-Ring: Class VI: 70A Silicone
2
13
Air Inlet Filter w/1/4" NPT male ends (gamma
stable)
1
14
Poly Tube: 1/4" ID x 3/8" OD: White
1
15
GE ReadyMate to 1" TC
3
16
GE ReadyMate to 3/4" TC
1
17
1" TC 90 Deg Elbow PVDF
1
18
1" TC BioClamp: Glass Filled Nylon
8
19
0.75" TC BioClamp: Glass Filled Nylon
1
20
O-Ring: Silicone: Size 207
1
21
3/8" Tube Push-to-Connect x 1/4 NPT Male
1
22
3/8" Tube Push-to-Connect x 1/4 NPT Female
2
23
1" Silicone Sanitary Gasket
4
24
XCell ATF 6 Branding Label
1
25
Henkel Loctite AA-3944 UV Adhesive: 25ml
syringe
1
26
Roll: Poly Tube: LDPE: 6 Mil Heavy Duty: 20" x 500'
1
27
Gamma Radiation Sterilization Indicator Labels
1
28
Box: Shipping: Single Use ATF6
1
29
Tie Wrap
9

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XCellTM ATF System with C410:V3 Controller
User Guide
Figure 4e. Exploded View of XCell™ ATF 4 System Filtration Assembly (P/N XCell™ ATF4:PH-
GMP)