cytiva UniFlux10 User manual

UniFlux10
Operating Instructions
Original instructions
cytiva.com

Table of Contents
1Introduction ........................................................................................................ 5
1.1 About this manual ......................................................................................................................................... 6
1.2 Important user information ....................................................................................................................... 7
1.3 Associated documentation ....................................................................................................................... 9
1.4 Abbreviations .................................................................................................................................................. 10
2 Safety instructions ............................................................................................. 11
2.1 Safety precautions ........................................................................................................................................ 12
2.2 Labels ................................................................................................................................................................. 22
2.3 Emergency procedures ............................................................................................................................... 25
3 System description ............................................................................................ 28
3.1 Configurations ................................................................................................................................................ 29
3.2 Illustrations ...................................................................................................................................................... 30
3.3 Standard components ................................................................................................................................. 35
3.3.1 Structural components .............................................................................................................................. 36
3.3.2 Control system components ................................................................................................................... 38
3.3.3 Connections and drains ............................................................................................................................. 39
3.3.4 Feed pump and feed line ........................................................................................................................... 41
3.3.5 Retentate line ................................................................................................................................................. 42
3.3.6 Permeate line ................................................................................................................................................. 43
3.3.7 Air integrity test device .............................................................................................................................. 45
3.3.8 Feed tank ......................................................................................................................................................... 46
3.4 Optional components .................................................................................................................................. 47
3.4.1 Peristaltic pumps .......................................................................................................................................... 48
3.4.2 Multiple inlets ................................................................................................................................................. 49
3.4.3 UV monitor ...................................................................................................................................................... 50
3.4.4 pH sensor ......................................................................................................................................................... 51
3.4.5 Conductivity sensor ..................................................................................................................................... 52
3.4.6 Feed tank mixer ............................................................................................................................................ 53
3.5 Filter cassette configuration ..................................................................................................................... 54
3.5.1 Filter cassette components ..................................................................................................................... 55
3.5.2 Cassette holder ............................................................................................................................................. 56
3.5.3 Filter cassettes .............................................................................................................................................. 58
3.6 Hollow fiber (HF) configuration ................................................................................................................. 59
3.6.1 UniFlux 10 HF configuration .................................................................................................................... 60
3.6.2 HF cartridges .................................................................................................................................................. 61
3.7 Meters and sensors ....................................................................................................................................... 63
3.7.1 Pressure ............................................................................................................................................................ 64
3.7.2 Flow .................................................................................................................................................................... 65
3.7.3 pH, conductivity and UV ............................................................................................................................. 66
3.7.4 Temperature .................................................................................................................................................. 67
3.7.5 Tank mass balance ...................................................................................................................................... 68
3.7.6 More information .......................................................................................................................................... 69
3.8 Flowchart .......................................................................................................................................................... 70
3.9 UNICORN control system ........................................................................................................................... 74
Table of Contents
2 UniFlux 10 Operating Instructions 28993587 AF

4 Installation .......................................................................................................... 78
4.1 Site requirements .......................................................................................................................................... 79
4.2 Transport .......................................................................................................................................................... 81
4.3 Unpacking ......................................................................................................................................................... 82
4.4 UniFlux 10 Setup ............................................................................................................................................ 84
4.4.1 Lock the wheels ............................................................................................................................................. 85
4.4.2 Stand-alone computer ............................................................................................................................... 86
4.4.3 Setup of control system and network .................................................................................................. 87
4.4.4 Connect compressed air supply ............................................................................................................. 88
4.4.5 Filter setup, feed pump and CFF filter protection ........................................................................... 90
4.5 Power supply .................................................................................................................................................... 91
5 Operation ............................................................................................................ 95
5.1 Prepare the system ....................................................................................................................................... 97
5.1.1 Sample handling ........................................................................................................................................... 98
5.1.2 Start the system and software ................................................................................................................ 101
5.1.3 Install hollow fiber cartridges .................................................................................................................. 103
5.1.4 Install filter cassettes .................................................................................................................................. 104
5.1.5 Testing ............................................................................................................................................................... 105
5.2 Calibrations ...................................................................................................................................................... 108
5.2.1 Preparing mass measuring ...................................................................................................................... 109
5.2.2 Establishing and entering holdup volume ......................................................................................... 110
5.2.3 Meter range and calibration .................................................................................................................... 111
5.3 Perform a run ................................................................................................................................................... 112
5.4 Procedures after usage ............................................................................................................................... 114
6 Maintenance ....................................................................................................... 115
6.1 User maintenance schedule ...................................................................................................................... 117
6.2 Cleaning ............................................................................................................................................................ 119
6.2.1 Important considerations for cleaning ................................................................................................ 121
6.2.2 Cleaning-in-place (CIP) .............................................................................................................................. 123
6.3 Storage .............................................................................................................................................................. 124
6.4 Disassembly and assembly ........................................................................................................................ 127
6.5 pH calibration .................................................................................................................................................. 129
6.6 Repair and calibration .................................................................................................................................. 131
6.7 Change filter type .......................................................................................................................................... 133
7 Troubleshooting ................................................................................................. 138
8 Reference information ....................................................................................... 145
8.1 Specifications .................................................................................................................................................. 146
8.2 Signals ................................................................................................................................................................ 150
8.3 Battery limits ................................................................................................................................................... 151
8.4 Chemical resistance ..................................................................................................................................... 153
8.5 Recycling information .................................................................................................................................. 155
8.6 Regulatory information ............................................................................................................................... 156
8.6.1 Contact information .................................................................................................................................... 157
8.6.2 European Union and European Economic Area .............................................................................. 158
8.6.3 Eurasian Economic Union
Евразийский экономический союз .................................................................................................. 159
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UniFlux 10 Operating Instructions 28993587 AF 3

8.6.4 Regulations for North America ............................................................................................................... 161
8.6.5 Regulatory statements .............................................................................................................................. 162
8.6.6 Declaration of Hazardous Substances (DoHS) ................................................................................ 163
8.6.7 Other regulations and standards .......................................................................................................... 165
8.7 Further information ...................................................................................................................................... 166
8.8 Health and Safety Declaration Form ...................................................................................................... 167
Appendix A: Create a method with UNICORN 5 ...................................................... 169
A.1 The Method Editor ..................................................................................................................................... 170
A.1.1 Introduction to the Method Editor .................................................................................................... 171
A.1.2 Method Editor layout .............................................................................................................................. 173
A.1.3 Other Method Editor features ............................................................................................................ 175
A.2 An example of using the Method Editor ............................................................................................ 176
A.2.1 Introduction .................................................................................................................................................... 177
A.2.2 Create the method ....................................................................................................................................... 179
A.2.3 Block 1: Initial conditions ........................................................................................................................... 182
A.2.4 Block 2: Product transfer ........................................................................................................................... 185
A.2.5 Block 3: Fed-batch concentration ......................................................................................................... 191
A.2.6 Saving the method ....................................................................................................................................... 201
Appendix B: Create a method with UNICORN 6 and above .................................... 202
B.1 The Method Editor ..................................................................................................................................... 203
B.1.1 Introduction to the Method Editor .................................................................................................... 204
B.1.2 Method Editor layout ............................................................................................................................... 206
B.1.3 Other Method Editor features ............................................................................................................. 208
B.2 An example of using the Method Editor ............................................................................................ 209
B.2.1 Introduction .................................................................................................................................................... 210
B.2.2 Create the method ....................................................................................................................................... 212
B.2.3 Phase 1: Method Settings ......................................................................................................................... 214
B.2.4 Phase 2: Product Transfer ......................................................................................................................... 218
B.2.5 Phase 3: Fed Batch Concentration ........................................................................................................ 224
B.2.6 Saving the method ....................................................................................................................................... 235
Appendix C: Evaluation for UNICORN 5 ................................................................... 236
Appendix D: PID control and feedback tuning ........................................................ 239
D.1 Introduction ..................................................................................................................................................... 240
D.2 Using PID control ........................................................................................................................................... 242
D.3 More information ........................................................................................................................................... 243
Index ........................................................................................................................... 245
Table of Contents
4 UniFlux 10 Operating Instructions 28993587 AF

1 Introduction
About this chapter
This chapter contains important user information, descriptions of safety notices,
intended use of the UniFlux™ 10 system and a list of associated documentation.
In this chapter
Section See page
1.1 About this manual 6
1.2 Important user information 7
1.3 Associated documentation 9
1.4 Abbreviations 10
1 Introduction
UniFlux 10 Operating Instructions 28993587 AF 5

1.1 About this manual
Purpose of this manual
The Operating Instructions provide you with the information needed to install, operate,
and maintain the product in a safe way.
Scope of this manual
This Operating Instructions covers all variants of UniFlux 10 system.
The components included in the configuration are described in the General Specifica-
tion (GS). Classification information for your system is described on the system label.
Typographical conventions
Software items are identified in the text by bold italic text.
Hardware items are identified in the text by bold text.
In electronic format, references in italics are clickable hyperlinks.
1 Introduction
1.1 About this manual
6 UniFlux 10 Operating Instructions 28993587 AF

1.2 Important user information
Read this before operating the
product
All users must read the entire Operating Instructions before installing, oper-
ating or maintaining the product.
Always keep the Operating Instructions at hand when operating the product.
Do not operate the product in any other way than described in the user documenta-
tion. If you do, you may be exposed to hazards that can lead to personal injury and you
may cause damage to the equipment.
Intended use of UniFlux 10 system
UniFlux 10 system is intended for pilot to production scale biological separations.
The systems are configured to operate hollow fiber cartridges suited for microfiltration
applications such as cell clarification/harvesting, or cassettes/hollow fibers for ultrafil-
tration applications, such as protein concentration and diafiltration in downstream
unit operations.
UniFlux 10 system shall not be used in any clinical procedures, or for diagnostic
purposes.
UniFlux 10 system shall not be used for operation in a potentially explosive atmosphere
or for handling flammable liquids.
WARNING
Do not operate the product in any other way than described in the
user documentation.
1 Introduction
1.2 Important user information
UniFlux 10 Operating Instructions 28993587 AF 7

Prerequisites
In order to operate UniFlux 10 system in a safe way, and according to the intended
purpose, the following prerequisites must be met:
•You should be acquainted with the use of bioprocessing equipment and with the
handling of biological materials.
•You must have read and understood the Safety chapter of these Operating Instruc-
tions.
•The system must be installed according to the instructions in Chapter 4 Installation,
on page 78.
•You must have a working knowledge of the UNICORN™ software. Refer to the
UNICORN manuals for instructions on the software structure and the work flow.
Safety notices
This user documentation contains safety notices (WARNING, CAUTION, and NOTICE)
concerning the safe use of the product. See definitions below.
WARNING
WARNING indicates a hazardous situation which, if not avoided,
could result in death or serious injury. It is important not to proceed
until all stated conditions are met and clearly understood.
CAUTION
CAUTION indicates a hazardous situation which, if not avoided,
could result in minor or moderate injury. It is important not to
proceed until all stated conditions are met and clearly understood.
NOTICE
NOTICE indicates instructions that must be followed to avoid
damage to the product or other equipment.
Notes and tips
Note: A note is used to indicate information that is important for trouble-free and
optimal use of the product.
Tip: A tip contains useful information that can improve or optimize your proce-
dures.
1 Introduction
1.2 Important user information
8 UniFlux 10 Operating Instructions 28993587 AF

1.3 Associated documentation
System-specific documentation
In addition to the Operating Instructions, the documentation package supplied with
the UniFlux 10 system also includes product documentation binders containing
detailed specifications and traceability documents. The most important documents in
the document package with regard to technical aspects of the UniFlux 10 system are:
Document Abbrevia-
tion
Purpose/Contents
Piping and Instrumen-
tation Diagram
P&ID Schematic overview of the entire
process flow, all components and
instruments and the control system.
General Specification GS Technical data for the system.
Assembly Drawing AD Physical layout. Provides all dimen-
sional data.
Bill of Material BOM Detailed specifications for process
related components.
Declaration of
Conformity
DoC EU declaration of conformity.
Spare Part List SPL List of spare parts available from Cytiva.
Software documentation
Together with each system, the following software documentation is supplied
providing additional information that applies to UniFlux 10 system, independent of the
specific configuration:
Document Purpose/Contents
UNICORN™ manual package •The manuals contain detailed instructions on
how to administer UNICORN, work with
methods, perform runs and evaluate results.
•The Online help contains dialog descriptions for
UNICORN. The Online help is accessed from the
Help menu.
Component documentation
Documentation for components produced both by Cytiva and by a third-party are, if
existent, also included in the product documentation package.
1 Introduction
1.3 Associated documentation
UniFlux 10 Operating Instructions 28993587 AF 9

1.4 Abbreviations
Introduction
This section explains abbreviations that appear in the user documentation for UniFlux
10.
Abbreviations
Abbrevia-
tion
Definition (English) Translation
EPDM Ethylene Propylene Diene
Monomer
Ethylene Propylene Diene
Monomer
HEPA High Efficiency Particulate Air High Efficiency Particulate Air
PID Proportional Integral Deriva-
tive
A PID controller calculates an
error value as the difference
between a measured process
variable (PV) and a desired
setpoint (SP). The PID
controller attempts to mini-
mize the error by adjusting the
process control inputs (CV).
Proportional Integral Deriva-
tive
A PID controller calculates an
error value as the difference
between a measured process
variable (PV) and a desired
setpoint (SP). The PID
controller attempts to mini-
mize the error by adjusting the
process control inputs (CV).
PLC Programmable logic controller Programmable logic controller
PV Process variable, measured Process variable, measured
SP Setpoint
The target value that an auto-
matic control system, for
example PID controller, will
attempt to reach by adjusting
the process control inputs.
Setpoint
The target value that an auto-
matic control system, for
example PID controller, will
attempt to reach by adjusting
the process control inputs.
TC-clamp Hygienic tubing connection
clamp
Hygienic tubing connection
clamp
UPS Uninterruptible power supply Uninterruptible power supply
1 Introduction
1.4 Abbreviations
10 UniFlux 10 Operating Instructions 28993587 AF

2 Safety instructions
About this chapter
This chapter describes safety precautions, emergency shutdown procedures and
labels information for UniFlux 10
In this chapter
Section See page
2.1 Safety precautions 12
2.2 Labels 22
2.3 Emergency procedures 25
Important
WARNING
Before installing, operating or maintaining the product, all
users must read and understand the entire contents of this
chapter to become aware of the hazards involved.
2 Safety instructions
UniFlux 10 Operating Instructions 28993587 AF 11

2.1 Safety precautions
Introduction
The safety precautions in this section are grouped in the following categories:
•General precautions on page 12
•Flammable liquids and explosive environment, on page 14
•Personal protection on page 14
•Installing and moving on page 15
•Power supply, on page 18
•System operation on page 18
•Maintenance on page 20
Note: Some of the safety precautions in this chapter may concern components or
situations described in other UniFlux 10 product documents.
General precautions
WARNING
Risk assessment. Perform a risk assessment for any risks due to
the process or process environment. Evaluate the effects the use of
the product and the operational processes may have on the classi-
fication of the hazardous area. The process might cause the area to
increase or the zone classification to change. Implement the risk
reduction measures needed, including use of personal protective
equipment.
WARNING
The customer must make sure that all installation, maintenance,
operation and inspection is carried out by qualified personnel who
are adequately trained, understand and adhere to local regulations
and the operating instructions, and have a thorough knowledge of
the product and the entire process.
WARNING
Do not operate the product in any other way than described in the
user documentation.
2 Safety instructions
2.1 Safety precautions
12 UniFlux 10 Operating Instructions 28993587 AF

WARNING
Protective earth. The product must always be connected to
protective earth when energized.
WARNING
Do not use UniFlux 10 system if it is not working properly, or if it has
suffered any damage, for example:
•damage to the power cord or its plug
•damage caused by dropping the equipment
•damage caused by splashing liquid onto it
WARNING
Only authorized personnel may open the electrical cabinet doors.
There is hazardous voltage inside the electrical cabinet that can
cause human injury or death.
WARNING
The electrical cabinet doors may only be opened when the product
is taken out of operation and subject to LOCK OUT / TAG OUT
(LOTO) (lockout-tagout).
CAUTION
Hot surface. When pumping fluid through the system that has a
temperature above the normal working temperature, do not touch
the system until you are sure that this can be done without risk and
when all components in the system have reached the normal
working temperature range.
CAUTION
Do not insert your fingers or other objects into fans or other
moving parts.
2 Safety instructions
2.1 Safety precautions
UniFlux 10 Operating Instructions 28993587 AF 13

Flammable liquids and explosive
environment
WARNING
Flammable liquids. This product is not approved to handle flam-
mable liquids.
WARNING
Explosive environment. The product is not approved for work in
a potentially explosive atmosphere. The product does not fulfill the
requirements of the ATEX Directive.
Personal protection
WARNING
Hazardous substances and biological agents. When using
hazardous chemical and biological agents, take all suitable protec-
tive measures, such as wearing protective clothing, glasses and
gloves resistant to the substances used. Follow local and/or
national regulations for safe operation and maintenance of UniFlux
10 system.
WARNING
Personal Protective Equipment (PPE). Whenever packing,
unpacking, transporting or moving the system, wear protective
footwear, preferably with steel toe caps.
WARNING
High pressure. The product operates under high pressure. Wear
protective glasses and other required Personal Protective Equip-
ment (PPE) at all times.
2 Safety instructions
2.1 Safety precautions
14 UniFlux 10 Operating Instructions 28993587 AF

Installing and moving
WARNING
The product must be installed and prepared by Cytiva personnel or
a third party authorized by Cytiva.
WARNING
Move transport crates. Make sure that the lifting equipment has
the capacity to safely lift the crate weight. Make sure that the crate
is properly balanced so that it will not accidentally tip when moved.
WARNING
The system is not fitted with lifting eye bolts or other equipment for
lifting with telphers or similar equipment. The system should only
be lifted using the lower part of the frame.
WARNING
Heavy object. Because of the significant weight of the product,
great care must be taken not to cause squeezing or crushing inju-
ries during movement. At least two, but preferably three or more,
people are recommended when moving the unit.
WARNING
Heavy object. The ramp is not reinforced in the center. Do not use
a pallet lifter or forklift on the ramp.
WARNING
Heavy object. When rolling the system down the ramp take great
care to avoid the wheels slipping off the edge of the ramp.
2 Safety instructions
2.1 Safety precautions
UniFlux 10 Operating Instructions 28993587 AF 15

WARNING
Access to power switch and power cord with plug. Do not
block access to the power switch and power cord. The power switch
must always be easy to access. The power cord with plug must
always be easy to disconnect.
WARNING
Fixed power supply: Access to power switch and isolation
switch. The power switch and the isolation switch must always be
easy to access.
WARNING
When the system is operated from a remote controlling computer,
the operator must always make sure that no one is present and
exposed when the system is started and that no one enters the risk
area around the system during operation.
CAUTION
The wheels of the product must be locked during normal use. The
wheels must be unlocked only when moving the unit.
CAUTION
Make sure that all tubing, hoses and cables are placed so that the
risk of tripping accidents is minimized.
CAUTION
The product is designed for indoor use only.
CAUTION
Do not use the product in a dusty atmosphere or close to spraying
water.
2 Safety instructions
2.1 Safety precautions
16 UniFlux 10 Operating Instructions 28993587 AF

CAUTION
Make sure that correct air pressure is always maintained. Too high
or too low air pressure may be hazardous and may cause erroneous
results and leakage.
CAUTION
Before moving the UniFlux 10 system, make sure that:
1. The power supply to the system is switched off.
2. All power cords to the systems are disconnected.
3. All air supply lines to the systems are disconnected.
4. All process lines to the systems are disconnected.
5. All communication cables to the systems are disconnected.
CAUTION
Make sure that the common waste outlet is:
•Never exposed to back-pressure.
•Connected to piping with at least the same diameter as the
common waste outlet piping.
•Connected to piping that allows maximum waste flow to be
transported away from the product without pooling.
CAUTION
Use the supplied network cable with encased RJ45 connectors to
protect from liquids. Do not replace this cable with an unprotected
cable.
CAUTION
To prevent bacterial growth, the product may be partly filled with
denatured alcohol (18% C2H5OH (ethanol), 2% C3H7OH (isopro-
panol) and 80% H2O (water)) at delivery.
The denatured alcohol mixture can be hazardous to humans
if consumed.
Flush out the denatured alcohol before assembling, testing or inte-
grating the product into the intended process context.
2 Safety instructions
2.1 Safety precautions
UniFlux 10 Operating Instructions 28993587 AF 17

NOTICE
Any computer used with the equipment must comply with EN/IEC
60950-1, and be installed and used according to the manufactur-
er's instructions.
Power supply
WARNING
Protective ground. The product must always be connected to a
grounded power outlet.
WARNING
National Codes and standards (NEC, VDE, BSI, IEC, UL etc.) and local
codes outline provisions for safely installing electrical equipment.
Installation must comply with specifications regarding wire types,
conductor sizes, plugs, branch circuit protection and disconnect
devices. Non-compliance may result in personal injury and/or
equipment damage.
WARNING
All electrical installations must be performed by authorized
personnel only.
CAUTION
Connection of an external Uninterruptible Power Supply (UPS)
(uninterrupted power supply) for system operation shall only be
performed by authorized personnel to avoid mismatching or
connection errors. Contact your local Cytiva representative for
more information.
System operation
WARNING
Safe distance. Always maintain a safe distance from UniFlux 10
system during drainage or other activities that may involve
splashing.
2 Safety instructions
2.1 Safety precautions
18 UniFlux 10 Operating Instructions 28993587 AF

WARNING
During operation, all cabinet doors must be closed and locked.
WARNING
Before operation, all process connections and the piping system
must be tested for leakage at maximum pressure for continued
protection against injury risks due to fluid jets, burst pipes or
potentially explosive atmosphere.
WARNING
Use a harmless fluid in the beginning of the process. This will make
it possible to detect leakage with minimized consequences and the
risk for potential leakage of hazardous fluids is avoided.
WARNING
Never exceed the operating limits stated in this document and on
the system label. Operation of the product outside these limits can
damage equipment and cause personal injury or death.
WARNING
Power failure - equipment may remain pressurized. During a
power failure, or if the EMERGENCY STOP button is pressed, the
equipment may remain pressurized. Opening a line or vessel at this
point could result in the release of potentially hazardous process or
cleaning fluid, and cause bodily harm.
When recovering from a power failure or emergency shutdown,
make sure all lines and vessels are depressurized before opening.
WARNING
Shutdown does not automatically result in depressurizing of the
piping system.
2 Safety instructions
2.1 Safety precautions
UniFlux 10 Operating Instructions 28993587 AF 19

WARNING
Emergency stop. Pressing the EMERGENCY STOP will not shut
off mains power to the electrical cabinet.
WARNING
Alarm signals. All alarm signals must be set within the limits
specified in the system documentation. Pressure and temperature
control must be activated while the system is in use to prevent
leakage or damage to the piping system.
WARNING
Alarm signals. Make sure to change back to the original alarm
level after UNICORN for BioProcess alarm buzzer test.
CAUTION
Make sure that the pH probe is mounted correctly after reas-
sembly.
CAUTION
The operator must always make sure that no one is present and
exposed before energizing the hydraulic pump.
Maintenance
WARNING
Decontaminate before service. Before performing any service
work on the system, make sure that the system has been properly
decontaminated.
2 Safety instructions
2.1 Safety precautions
20 UniFlux 10 Operating Instructions 28993587 AF