Miltenyi Biotec CliniMACS Plus System User manual

CliniMACS® Plus Instrument
User Manual

The CliniMACS System components, including Reagents, Tubing Sets, Instruments, and PBS/EDTA Buffer, are designed,
manufactured and tested under a quality system certified to ISO 13485. In the EU, the CliniMACS System components are
available as CE-marked medical device for their respective intended use, unless otherwise stated. In the US, the CliniMACS CD34
Reagent System, including the CliniMACS Plus Instrument, CliniMACS CD34 Reagent, CliniMACS Tubing Set TS and CliniMACS
Tubing Set LS, and the CliniMACS PBS/EDTA Buffer, is FDA approved as a Humanitarian Use Instrument (HUD), authorized by U.S.
Federal law for use in the treatment of patients with acute myeloid leukemia (AML) in first complete remission. The effectiveness
of the device for this indication has not been demonstrated. Other products of the CliniMACS Product Line are available for use
only under an approved Investigational New Drug (IND) application, Investigational device Exemption (IDE) or FDA approval. In
Australia, the following components of the CliniMACS Plus System are included in the Australian Register of Therapeutic Goods
(ARTG) and are therefore approved for supply: CliniMACS Plus Instrument, CliniMACS CD34 Reagent, CliniMACS Tubing Set,
CliniMACS Tubing Set LS, CliniMACS Depletion Tubing Set, and CliniMACS PBS/EDTA Buffer. Only those products which are
included in the ARTG may be used in Australia.
Unless otherwise specifically indicated, Miltenyi Biotec products and services are for research use only and not for therapeutic or
diagnostic use.
Copyright © 2022 Miltenyi Biotec and/or its affiliates. All rights reserved.
No part of this publication may be reproduced, stored in a retrieval system, transmitted, published, or distributed in any form or by
any means, electronically, mechanically, by photocopying, microfilming, recording, or otherwise, without the prior written consent of
Miltenyi Biotec; however, notwithstanding the foregoing, the owners of the instrument may make copies solely for purposes of
training personnel in the use and servicing of the unit within their business or organization.
CliniMACS, MACS, and the Miltenyi Biotec logo are registered trademarks or trademarks of Miltenyi Biotec B.V. & Co. KG and/or its
affiliates in various countries worldwide. All other trademarks mentioned in this document are the property of their respective
owners and are used for identification purposes only.

CliniMACS® Plus Instrument
User Manual
Software version 2.4x
Issued: 2022-11
210-003-188/02
Miltenyi Biotec B.V. & Co. KG
Friedrich-Ebert-Straße 68
51429 Bergisch Gladbach
Germany
Miltenyi Biotec Technical Support
[phone]
technicalsuppor[email protected]
www.miltenyibiotec.com

3
Essential information
This user manual provides information for the use of the CliniMACS Plus Instrument.
For further details on the processes running on the instrument, refer to the
CliniMACS Plus Applications User Manual.
The operation of the CliniMACS Plus System must be performed by trained
operators only. Before putting the system into operation, carefully read and
understand the safety information, warnings, precautions, and instructions
for proper operation of the CliniMACS Plus Instrument provided in the
instructions for use of the CliniMACS Plus System components (including,
without limitation, the safety information in this user manual, chapter 3
“Importantsafety information”) and in any safety-related recommendations
issued by Miltenyi Biotec. Pay special attention to all warnings displayed on
the instrument or provided with consumables and accessories. The operator
must adhere to all instructions and procedures at all times during the
operation of the instrument, confirming that all safety information,
warnings, precautions, and instructions are observed. Failure to follow the
safety information, warnings, precautions, and instructions contained in
the instructions for use could result in instrument malfunction, property
damage, personal injury, and/or death. Equipment safety may be
compromised if the instrument is not used according to the manufacturer’s
instruction.
Retain the CliniMACS Plus Instrument instructions for use for future
reference. They should be kept accessible and readily available together
with all other safety and operating documentation during the entire life
cycle of the instrument for all personnel responsible for installation,
operation, and maintenance.

4

5
1 Introduction 7
1.1 General information 7
1.2 CliniMACS Plus Instrument information 8
2 Glossary 9
2.1 Graphical depiction 9
2.2 Glossary of symbols 10
2.2.1 Safety symbols 10
2.2.2 Symbols used for labeling products 10
2.3 Glossary of terms 13
3 Important safety information 15
3.1 Safety instructions for the CliniMACS Plus Instrument 17
3.1.1 Usage and installation 17
3.1.2 Electric hazards 18
3.1.3 Strong magnetic field 20
3.1.4 Biological hazards 20
3.1.5 Mechanical hazard 20
3.1.6 Servicing and transport 21
4 The CliniMACS Plus Instrument 23
4.1 Regulatory information 23
4.2 Intended purpose 23
4.3 Technical data 24
4.4 Power connection 25
4.5 Unpacking 26
4.6 Transport 27
4.7 Positioning 27
4.8 Cleaning and disinfection 28
4.9 Maintenance 28
Table of contents

6
4.10 Disposal 29
4.11 Description 29
4.12 Installation 31
4.12.1 Connect and switch on the CliniMACS Plus Instrument 31
4.12.2 Language selection and service menu 32
4.13 General set-up menus 32
5 The CliniMACS Plus System 35
5.1 CliniMACS Plus Instrument 35
5.2 CliniMACS Reagents and Biotin Conjugates 35
5.3 CliniMACS Plus Tubing Sets 35
5.4 CliniMACS PBS/EDTA Buffer 35
5.5 Additional materials required 35
6 Troubleshooting 37
6.1 Miltenyi Biotec Technical Support 37
6.2 Error messages 37
7 Legal notes 39
7.1 Limited warranty 39
7.2 Trademarks 40
Appendix 41

7
INTRODUCTION INTRODUCTION
1 Introduction
1.1 General information
The CliniMACS Plus System offers a set of tools making high quality standard cell
separations available for therapeutic applications.
LIMITED WARRANTY
Should the CliniMACS Plus System be used in a manner not explicitly described in
this manual, all warranties will be null and void.
The CliniMACS Plus System is based on the magnetic cell separation technology
(MACS® Technology) developed by Miltenyi Biotec B.V. & Co. KG. Miltenyi Biotec has
made these products available for clinical applications meeting the requirements
of European Regulatory Standards.
The CliniMACS Reagents and Biotin Conjugates are intended for in vitro use only
and are not designated for therapeutic use or direct infusion into patients.
The CliniMACS Reagents in combination with the CliniMACS Plus System are
intended to separate human cells.
Miltenyi Biotec as the manufacturer of the CliniMACS Plus System does not give any
recommendations regarding the use of separated cells for therapeutic purposes
and does not make any claims regarding a clinical benefit.
For the manufacturing and use of target cells in humans the national legislation
and regulations – e.g., for the EU the Directive 2004/23/EC (human tissues and cells)
or the Directive 2002/98/ EC (human blood and blood components) – must be
followed. Thus, any clinical application of the target cells is exclusively within the
responsibility of the user of a CliniMACS Plus System.
IMPORTANT
Before using the CliniMACS Plus System or any components outside the European
Economic Community, the regulatory approval of the CliniMACS Plus System or any
CliniMACS Component in the country must be confirmed.

8
INTRODUCTION INTRODUCTION
1.2 CliniMACS Plus Instrument information
Record below the serial number located on the back of the CliniMACS Plus
Instrument. Refer to these numbers when calling Miltenyi Biotec Technical Support
to obtain information or request service on the instrument.
Model no:
Serial no:
Software version:

9
GLOSSARY GLOSSARY
2 Glossary
2.1 Graphical depiction
The following chart depicts the panels used in this user manual to inform the user
about potential risks if the outlined warnings and precautions are not followed.
The hazard level classifies the hazard, as described below. The level, type, and
source of the hazard, as well as potential consequences, prohibitions, and measures
are indicated as follows. Icons on the left side specify the risk.
Indicates a hazardous situation that, if not avoided, could result in death or
serious injury
Indicates a hazardous situation that, if not avoided, could result in minor or
moderate injury
Indicates information considered important, but not hazard-related (e.g., messages
relating to property damage)
IMPORTANT
Advises the user of important practices or information not related to personal injury nor
property damage

10
GLOSSARY GLOSSARY
2.2 Glossary of symbols
2.2.1 Safety symbols
General warning sign
Warning: Electricity
Warning: Magnetic field
Warning: Biological hazard
Warning: Crushing of hands
2.2.2 Symbols used for labeling products
European conformity approval with ID number 0123 (ID
number of Notified Body: “TÜV SÜD Product Service GmbH,
Munich”)
Medical Device
Eurasian Conformity mark
UK Conformity Assessed mark
UL listing mark, listed as laboratory equipment
Consult instructions for use
Caution
Strong magnetic field
Manufacturer

11
GLOSSARY GLOSSARY
Date of manufacture
Non-ionizing radiation
Separate collection for waste of electrical and electronic
equipment
Fuse
Keep dry
Fragile, handle with care
This way up
Power OFF
Power ON
Do not re-use.
Do not use if package is damaged
The packaging is PVC free
Use-by date
Temperature limit
Non-pyrogenic fluid path
Batch code

12
GLOSSARY GLOSSARY
Part number
Contents of the packaging
Catalogue number
Serial number
Unique Device Identification
Sterilized using ethylene oxide
Sterilized using steam or dry heat
Single sterile barrier system
Single sterile barrier system with protective packaging outside
Phone
E-Mail
Website

13
GLOSSARY GLOSSARY
2.3 Glossary of terms
Compartment of the CliniMACS Plus Instrument in which the
Negative Fraction Bag and Buffer Waste Bag are placed
Support on the CliniMACS Plus Instrument to mount the Cell
Preparation Bag, Non-Target Cell Bag, Priming Waste Bag,
Reapplication Bag, and buffer bag
Set of tubing, connectors, columns, and bags through which the
magnetical labeled cell suspension is processed and in which
the magnetic cell separation takes place, especially designed for
the specific depletion needs
Buffer used for cell preparation and cell separation with the
CliniMACS Plus System: PBS (phosphate buffered saline),
supplemented with 1 mM EDTA, pH 7.2. Before use, CliniMACS
PBS/EDTA Buffer must be supplemented with pharmaceutical
grade HSA to a final concentration of 0.5% (weight/volume, i.e.,
5 g HSA per liter buffer)
Magnetic cell separation instrument based on the MACS
Technology
Set of tubing, connectors, columns, and bags through which the
magnetically labeled cell suspension is processed and in which
the magnetic cell separation takes place
Ethylene-diamine-tetra-acetic acid
Human serum albumin
Pharmaceutical grade HSA approved in your country is necessary
as a buffer supplement when used with the CliniMACS Plus
System.
Reaction of cells with magnetic labeling reagent, e.g., CliniMACS
CD34 Reagent to CD34 positive cells
Apheresis collecting leukocytes
Component of the CliniMACS Plus Instrument that detects liquid
in the tubing
A super-paramagnetically labeled antibody
Tubing pump used in the CliniMACS Plus Instrument to control
the flow rate of fluid in the tubing set
Bag compartment
Bag hanger
CliniMACS Depletion
Tubing Set
CliniMACS PBS/EDTA Buffer
CliniMACS Plus Instrument
CliniMACS Tubing Set,
CliniMACS Tubing Set LS
EDTA
HSA
Human serum albumin
Labeling
Leukapheresis
Liquid sensor
Magnetic antibody
Peristaltic pump

14
GLOSSARY GLOSSARY
First column in the CliniMACS Tubing Set and the CliniMACS
Tubing Set LS, serves as filter to trap cells having non-specific
interactions with the column matrix
Support mounted on the CliniMACS Plus Instrument that holds
the pre-column in place
Sensor that prevents pump operation when the pump door is
open
See separation column.
See separation column holder.
Column in which magnetically labeled cells are separated when
exposed to the magnetic field
Molded guides in the magnet housing that holds the separation
column in place
Software program designed for the enrichment or depletion of
magnetically labeled cell subsets from a mixed cell population.
Choose from a menu of separation programs depending on the
intended separation.
Reagent for magnetic labeling of cells, e.g., CliniMACS CD34
Reagent
White blood cells
Pre-column
Pre-column holder
Pump safety switch
Selection column
Selection column holder
Separation column
Separation column holder
Separation program
Separation reagent
WBC

15
IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION
3 Important safety information
The operation of the instrument must be performed by trained operators
only. Operator training will be provided by a Miltenyi Biotec representative.
Before putting the system into operation carefully read and understand the
safety information, warnings, precautions, and instructions for proper
operation of the CliniMACS Plus System provided in this user manual
(including without limitation the safety information in this chapter) and in
any safety-related recommendations issued by Miltenyi Biotec. Pay special
attention to all warnings displayed on the instrument or provided with
consumables and accessories. The operator must adhere to all safety
information, warnings, precautions, and instructions at all times when
putting the instrument into operation.
Retain the user manuals for future reference. They should be kept accessible and
readily available together with all other safety and operating documentation
during the entire life cycle of the instrument for all personnel responsible for
installation, operation, and maintenance.
Hazards to users, instrument damage, and/or malfunction, unpredictable
results, premature wear and tear, and/or reduced life time of the instrument
if the following safety information, warnings, precautions, and instructions
are not observed at all times when using the instrument.
• Always operate, handle, use, and maintain the instrument in accordance with
the safety information, warnings, precautions, instructions, and recommended
procedures provided in the user manuals and other written instructions issued
by Miltenyi Biotec. Do not deviate from these operating instructions and
procedures.
• Always ensure that the instrument is operated, handled, used, and maintained
only by appropriately skilled and trained personnel familiar with the
construction, operation, and hazards involved with the instrument. The
instrument is intended for the use in the professional facility healthcare
environment. The instrument is not intended to be used near active HF surgical
equipment. The customer or user should assure that it is used in such an
environment.
• Always operate, handle, use, and maintain the instrument in compliance with
all applicable laws, rules, regulations and administrative provisions, including,
without limitation, all regulations regarding health and safety at work and, as
appropriate, the safety of medical instruments, as applicable at the location
where the instrument is operated.
• Always use the instrument for its designated purpose (in accordance with the
product documentation and within its performance limits), and not in any other
manner or for any other purpose.

16
IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION
• Safety and performance of the instrument may be compromised. Never use the
instrument with consumables, accessories, and/or cables other than those
approved by Miltenyi Biotec to ensure safe and proper operation of the
instrument. Note: The use of consumables, accessories, and/or cables not
expressly approved by Miltenyi Biotec could void the warranty and/or invalidate
the authority to operate this instrument under applicable regulations.
• Always follow the maintenance recommendations of Miltenyi Biotec and
appropriate product standards. Note: Installation, maintenance and service of
the instrument must only be performed by authorized local Miltenyi Biotec
service provider. Confirm that the instrument is not put into operation unless
and until all initial and periodic maintenance, and instrument safety checks
have been successfully performed.
• Defects should be addressed immediately. If there is any doubt regarding the
proper functioning of the instrument, do not use the instrument and contact
the authorized local Miltenyi Biotec service provider or Miltenyi Biotec Technical
Support as soon as possible.
• Never change or modify the instrument except with Miltenyi Biotec’s prior
written approval. Note: Changes or modifications to the instrument not
expressly approved by Miltenyi Biotec could void the warranty and/or invalidate
the operator’s authority to operate the instrument under applicable regulations.
Risk of death, serious personal injury, and/or property damage,instrument
malfunction, or damage, premature wear and tear, and reduced instrument
life time. Failure to comply with the safety information, warnings,
precautions, and instructions in the user manuals (and in other safety
related publications issued by Miltenyi Biotec for use with the instrument)
could lead to improper or incorrect use, handling or care of the product and
cause a hazard, and could result in death, serious personal injury, and/or
property damage, instrument malfunction, or damage, premature wear and
tear, and reduced instrument life time, and may void the warranty and/or
invalidate the authority to operate the instrument under applicable
regulations. Miltenyi Biotec accepts no liability for consequences arising
from failure to comply with the safety information, warnings, precautions,
and instructions provided herein.
If concerned about the safe use of the instrument or additional safety information
regarding the CliniMACS PlusInstrument System is required, contact the authorized
local Miltenyi Biotec service provider or Miltenyi Biotec Technical Support.

17
IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION
3.1 Safety instructions for the CliniMACS Plus
Instrument
In the event of an unexpected process abortion or messages on the screen that
advises the operator to contact technical support, immediately contact the Miltenyi
Biotec Technical Support. If secure operation is no longer possible, immediately
switch off and unplug the instrument from the power outlet and contact Miltenyi
Biotec Technical Support or an authorized local Miltenyi Biotec service provider.
3.1.1 Usage and installation
Risk of improper operation due to increased electromagnetic emission or
decreased electromagnetic immunity. The use of consumables, accessories,
and cables other than those specified or provided by the manufacturer of
this equipment could result in increased electromagnetic emission or
decreased electromagnetic immunity of this equipment and result in
improper operation. Medical electrical equipment requires special
precautions regarding electromagnetic compatibility (EMC) and must be
installed and placed in service according to the EMC information (see
Appendix). Portable and mobile RF communications equipment can affect
medical electrical equipment. Only use the instrument with accessories,
transducers, and/or cables approved by Miltenyi Biotec. Installation of the
CliniMACS Plus Instrument must only be performed by an authorized local
Miltenyi Biotec service provider.
Risk of process failure. If alarm signals are not recognized and the required
actions are not executed or confirmed there is the risk of process failure. Confirm
that acoustical alarm signals can be recognized by the operator at any time
during the process.
The CliniMACS Plus Instrument may be used repeatedly. It is not intended for
disposal after single use.
Contact the local authority governing electrical power supply, building
construction,maintenance,orsafetyformoreinformationregardingtheinstallation
of the equipment.
Do not leave the instrument unattended during a run. If an error occurs, the cell
separation can be interrupted by the user at the current step and the operator will
have 600 seconds to correct certain errors. If the instrument has not been restarted
after this time period, the run will be aborted.
Keep away from all moving parts.

18
IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION
Risk of injury. If the separation column is inserted or removed while the
magnet unit is switched on, there is the risk of personal injury. Only insert or
remove the separation column when the magnet unit is switched off.
Risk of reduced quality of target cells. The target cells must be analyzed and
confirmed to meet user requirements, otherwise the suitability for clinical
application can be compromised. Examine the target cells regarding quality
and quantity according to their intended use.
Risk of damage to the bag hangers. Risk of damage to the bag hangers in case
of overloading. The carrying capacity of a single bag hanger is 3 kg. Do not
overload the bag hangers.
3.1.2 Electric hazards
The CliniMACS Plus Instrument is a Protection class I instrument and may only be
plugged into an outlet with a grounded connection.
Risk of electric shock, electrical short, and spread of fire. Electric shock may
lead to severe personal injury or death. The housing of the instrument
reduces the risks of electric shock, electrical short, and spread of fire.
Opening any cover of the instrument interrupts this protective measure. Do
not remove or penetrate any cover of the instrument. Only authorized local
Miltenyi Biotec service provider may open the instrument or exchange spare
parts. Do not use the instrument in case of visible damage or if it has been
dropped. Contact Miltenyi Biotec Technical Support.
Before cleaning or maintenance of the instrument, the power cord must be
disconnected. Use the mains plug to disconnect the instrument from the
power supply. Only use the originally supplied power cord.
If flames or smoke appear, immediately switch off the instrument, unplug it
from the electrical outlet, and contact an authorized local Miltenyi Biotec
service provider or Miltenyi Biotec Technical Support.
The instrument is intended for indoor use only. Water ingress may lead to an
electrical short and the risk of electric shock or spread of fire. Do not use the
instrument in a wet or damp location or if it has been exposed to moisture.
Avoid high humidity or condensation and protect the instrument from
contact with water. Special care must be taken while handling fluids. Clean
spillages immediately. Do not allow fluids to enter the interior of the
instrument. Avoid ingress of any liquid into the valves. Do not operate the
instrument if liquids have spilled into the instrument. Fluid containers must
be handled with caution when in the area of the instrument. After moving
the instrument from a cold environment, such as a cold room at +4 °C(+39 °F),