ThermoFisher DOC0031 User Manual
HyPerforma Single-Use Fermentor
(S.U.F.) User’s Guide
DOC0031 • Revision G
February 2021
Contents
Warnings, safety, and warranty information 1
How to use this guide 7
Chapter 1 Single-Use Fermentor (S.U.F.) overview 10
1.1 Introduction 11
1.2 Hardware characteristics 14
1.2.1 System features 14
1.2.2 Agitation 14
1.2.3 Control system 14
1.2.4 Exhaust management system 14
1.2.5 Exhaust vent filter heater 14
1.2.6 Temperature 15
1.2.7 Heating performance 15
1.2.8 External control 15
1.2.9 Load cells 15
1.3 End user and third-party supplied components 16
1.3.1 pH and dissolved oxygen (DO) probes 16
1.3.2 Single-use probes 16
1.3.3 Controllers 17
1.4 BioProcess Container characteristics 18
1.4.1 Single-Use Fermentor BPC features 18
1.4.2 Operating pressure 18
1.4.3 Working volume 18
1.4.4 Draining and harvest 19
1.4.5 Aeration 19
1.4.6 Aseptic connections 19
1.4.7 Sampling 19
1.4.8 BPC features 20
1.5 Additional system components 22
1.5.1 Probe integration 22
1.5.2 Accessories 22
Contents
Chapter 2 Installation and setup 24
2.1 Initial installation preparation 25
2.1.1 Hardware shipment and setup 25
2.2 Site preparation 25
2.2.1 Electrical connections for units with an electrical
control box 25
2.2.2 Outer support container preparation 26
2.2.3 Electrical preparation for systems with electrical
control boxes 26
2.2.4 Load cell preparation 27
2.3 Installation 28
2.3.1 Exhaust filter bracket setup 30
2.3.2 Condenser unit setup (when present) 31
2.3.3 TCU/chiller connection to condenser unit
(when present) 32
2.3.4 Exhaust filter pinch clamp setup (when present) 33
2.3.5 Optional cable management system setup 35
2.3.6 Air line preparation 35
2.3.7 Drilled hole sparger line(s) 35
Chapter 3 Operating information 36
3.1 General system operating information 37
3.1.1 BPC preparation and loading 37
3.1.2 BPC handling instructions 37
3.1.3 BPC operating information 37
3.1.4 Hardware operating information 39
3.2 BPC and drive shaft loading for 30 L units 43
3.2.1 Initial installation steps for 30 L units 43
3.2.2 Drive shaft insertion for 30 L units 51
3.2.3 Final installation steps for 30 L units 54
3.3 BPC and drive shaft loading for 300 L units 56
3.3.1 Initial installation steps for 300 L units 56
3.3.2 Drive shaft insertion for 300 L units 64
3.3.3 Final installation steps for 300 L units 69
3.4 Exhaust system 72
3.4.1 Exhaust system functional overview 72
3.4.2 When to use the condenser 73
3.4.3 Condensers and reserve vent filters 74
Contents
3.4.4 Exhaust system setup 74
3.4.5 Exhaust system setup 75
3.5 Probe assembly 79
3.5.1 Preparation and sterilization 79
3.5.2 Making CPC AseptiQuik connections 80
3.5.3 Probe insertion 83
3.5.4 Probe calibration 85
3.5.5 Kleenpak connection instructions 85
3.6 Microbial cell culture operating instructions 95
3.6.1 Operating conditions for cell culture applications 95
3.6.2 Manual operation of drilled hole spargers 96
3.6.3 Checkpoints prior to media fill 97
3.6.4 Media fill 97
3.6.5 Agitation for units with electrical control boxes 98
3.6.6 Temperature control 99
3.6.7 pH probe calibration 100
3.6.8 DO probe calibration 100
3.6.9 Checkpoints prior to inoculation 100
3.6.10 Cell inoculation 100
3.6.11 In-process checkpoints 101
3.6.12 Dispense and harvest 101
3.6.13 S.U.F. shutdown and post-use BPC disposal 102
3.6.14 Preparation for the next run 103
3.7 BPC sampling 104
3.7.1 Aseptic sampling 104
3.7.2 Sampling with sterile manifold 105
3.8 Verification procedures 107
3.8.1 Mixer speed verification 107
3.8.2 Temperature controller verification 107
3.8.3 Pressure monitor verification (when present) 107
3.8.4 Load cell verification (when present) 107
Chapter 4 Specifications and parts information 108
4.1 Hardware features and dimensions 109
4.1.1 30 L S.U.F. design features 109
4.1.2 300 L S.U.F. design features 110
4.1.3 30 L S.U.F. dimensions and ordering information 111
4.1.4 300 L S.U.F. dimensions and ordering information 112
Contents
4.2 30 L and 300 L S.U.F. hardware specifications 113
4.3 Configurable hardware options 115
4.4 BPC features and specifications 116
4.4.1 Standard 30 L S.U.F. BPC 116
4.4.2 Standard 300 L S.U.F. BPC 118
4.5 BPC options and packaging information 120
4.6 Accessories and options specifications 121
4.6.1 Load cells 121
4.6.2 Cable management system 124
4.6.3 Vent filter heaters 125
4.6.4 Exhaust system 126
4.6.5 Miscellaneous items 129
Chapter 5 Maintenance and troubleshooting 132
5.1 Maintenance 133
5.1.1 Routine maintenance 133
5.1.2 Preventive maintenance schedule 133
5.2 Troubleshooting and frequently asked questions 135
5.2.1 Hardware operation issues 135
5.2.2 Cell culture operation issues 137
5.2.3 Probe and connector issues 140
5.2.4 BPC and sparging issues 141
Chapter 6 General ordering information 142
6.1 Ordering instructions 143
6.2 Ordering/support contact information 143
6.3 Technical support 144
Appendices Appendix A—Installation of female electrical receptacle
for units with AC motors and electrical boxes 145
Appendix B—Mettler Toledo IND331 Display load cell
calibration instructions 148
Appendix C—Pre-fermentation run checklist 150
Warnings, safety, and warranty information
Warnings, safety, and warranty
information
Thank you for purchasing the Thermo Scientific™ HyPerforma™
Single-Use Fermentor (S.U.F.). We have included safety information in
this guide, based on our knowledge and experience. It is important,
however, for you to work with your Safety Management personnel to
ensure that this equipment is integrated into your safety practices.
Please take some time to perform your own job safety analysis in order
to identify and control each potential hazard.
WARNING: Read and understand this user’s guide before
operating this equipment.
The Thermo Scientific HyPerforma Single-Use Fermentor (S.U.F.)
is designed to be operated under traditional microbial cell culture
conditions. A general understanding of Fermentor systems and their
operation is important prior to using the system for the first time. Read
and understand user’s guide before operating; failure to do so could
result in injury. Proper procedures for the disposal of Single-Use
BioProcess Containers (BPCs) should be followed, depending on
the culture in use. See the appropriate section of this guide.
WARNING: Tipping hazard. The vessel should only be moved by
pushing using the provided handles or at the mid-point of the
vessel.
If pulled or moved too quickly, the vessel can tip, potentially leading
to damage to equipment or injury to personnel. To reduce the risk
of tipping, the vessel should only be moved slowly over smooth, flat
surfaces by at least two qualified personnel. During movement, any
locking feet should be retracted, and casters should be in the unlocked
position. The vessel should not be moved by pulling of any kind.
WARNING: Hazardous voltage inside.
Electrical components are required for the proper function of the
S.U.F. The mixer motor, motor controller, and control panel all have
electrical components. There is a risk of electrical shock and injury.
Disconnect power before opening electrical components. Service
by trained personnel only. Thermo Fisher Scientific recommends
using standard lockout procedures when working on electrical
components. The main breaker on the electrical control panel may
be locked out.
HyPerforma Single-Use Fermentor User’s Guide | 1Thermo Scientific
Warnings, safety, and warranty information
WARNING: Static electricity may build up in BPCs.
• BPCs may act as insulators for electrostatic charge. If electrostatic
• Where applicable, a product contact stainless steel coupler may be
WARNING: Rotating parts—entanglement hazard.
Rotating and moving parts can cause injury. Keep hands away from
moving parts.
• Do not operate this equipment unless the supplied guarding is in
• It is the responsibility of the end user to assess this equipment
charge is transferred to a BPC, the charge may be stored in
the BPC and/or the product inside. This phenomena varies by
product and use; therefore, it is the sole responsibility of the end
user to ensure a hazard assessment is conducted and the risk of
electrostatic shock is eliminated.
grounded to the frame to dissipate electrostatic build up from the
material within a BPC. It is good practice to dissipate electrostatic
build up by grounding all BPCs prior to coming in contact with
them. When working with BPCs, the use of nonconductive
materials, such as nonconductive gloves, is recommended.
place and properly functioning.
and ensure that equipment and safeguards are in good working
condition, and that all operators are trained and aware of
entanglement hazards and associated protective devices, such as
hazard signs and guarding.
WARNING: Use ladders and elevated platforms with caution.
A few operations, such as mounting the motor to the 300 L S.U.F.
during setup, may require the use of a ladder or platform. Before use,
ensure the ladder has been inspected and weight-rated for its user.
When using a ladder or platform, be sure it is stable, maintain three
points of contact and make sure the steps are clean.
WARNING: Follow lockout/tagout procedures.
To prevent injury, when servicing equipment, use your company’s
lockout/tagout procedures to isolate electrical, mechanical, pneumatic,
hydraulic, chemical, thermal, gravitational or any other potential energy
and protect workers from the release of hazardous energy.
WARNING: Use caution with hazardous chemicals or materials.
Personnel servicing equipment need to know the hazards of any
chemicals or materials that may be present on or in the equipment.
Use general hazard communication techniques such as Safety Data
Sheets, labels and pictograms to communicate any hazards.
HyPerforma Single-Use Fermentor User’s Guide | 2Thermo Scientific
Warnings, safety, and warranty information
WARNING: Hot surface—do not touch.
The heating jacket is designed to heat the inner vessel wall. Normal
operating conditions generate heat and could create hot surfaces.
• Hot surface inside
• Contact with surfaces may cause burns
• Do not touch while in operation
WARNING: The Thermo Scientific HyPerforma S.U.F. may not
be installed in a potentially explosive atmosphere as set forth
in the applicable EU ATEX Directive.
WARNING: Burst hazard.
The S.U.F. BPC chamber is under slight pressure under normal
operating conditions. Normal passive venting prevents any excess of
pressure building up within the chamber. Chamber pressure and inlet
line pressure should be monitored for proper settings.
• Do not exceed 0.03 bar (0.5 psi) pressure within the BPC
• Do not exceed 0.34 bar (5 psi) pressure in the section of BPC
• Make sure the vent filter is properly positioned and working
• Maintain a minimum gas flow of 0.1 vvm or 0.01 psi in the BPC
tubing between the inlet filter and the BPC
properly
while the impeller is spinning
Protective earth grounding
Protective earth grounding must be verified prior to plugging the
S.U.F. into any electrical outlet. Ensure the receptacle is properly earth
grounded.
Environmental conditions
• Operating: 17°C to 27°C; 20 to 80% relative humidity, noncondensing
• Storage: –25°C to 65°C
• Installation category II (over voltage) in accordance with IEC 664
• Altitude Limit: 2,000 meters
Water jacket vessel information
S.U.F. hardware unit with water jacket has been designed to be
operated with water as the heat transfer medium with temperatures not
exceeding 50°C (122°F) under 150 psig (1 MPa) operating pressure. For
the utmost safety it is recommended that the water jacketed S.U.F. be
operated at 75 psig or less.
HyPerforma Single-Use Fermentor User’s Guide | 3Thermo Scientific
Warnings, safety, and warranty information
Note: The S.U.F. BPC operating limits for temperature are 5°C to 40°C.
The internal pressure should not exceed .003 bar (0.5 psi). The water
jacket is not required to be registered, inspected and stamped with the
Code U symbol per section U-1(c)2(f) of the ASME Boiler and Pressure
Vessel Code and/or European Pressure Equipment Directive (PED)
97/23/EC. Upon request, a Declaration of Conformity, PED Sound
Engineering Practices can be made available.
Electrical connections
Power should be supplied by a non-GFCI 15 amp circuit. Ground
faults occur when current is leaking somewhere, in effect, electricity is
escaping to the ground. Electrocution can occur when the human
body serves as the path for the leakage to the ground. A Ground
Fault Circuit Interrupter (GFCI) senses the current flowing to the ground
and switches off the power (trips the GFCI) in a fraction of a second at
currents well below those that are considered dangerous. Due to the
sensitivity of GFCIs to electrical leakage (a few mA), it is recommended
that the S.U.F. not be plugged into a GFCI outlet.
Warranty information
Any warranties, if applicable, covering this equipment exclude: (a)
normal wear and tear; (b) accident, disaster or event of force majeure;
(c) your misuse, fault or negligence; (d) use of the equipment in a
manner for which it was not designed; (e) causes external to the
equipment such as, but not limited to, external puncturing, power
failure or electrical power surges; (f) improper storage and handling of
the equipment; (g) use of the equipment in combination with equipment
or software that we did not supply; (h) equipment sold to you as ‘used’
products; (i) contact with improperly used or unapproved chemicals
or samples; (j) installation, removal, use, maintenance, storage, or
handling in an improper, inadequate, or unapproved manner, such as,
but not limited to, failure to follow the documentation or instructions in
the deliverables or related to the equipment, operation outside of stated
environmental or other operational specifications, or operation with
unapproved software, materials or other products; (k) manufacture in
accordance with requirements you gave us; (l) installation of software
or interfacing or use of the equipment in combination with software
or products we have not approved; (m) use of the deliverables
or any documentation to support regulatory approvals; (n) the
performance, efficacy or compatibility of specified components; and
(o) the performance of custom equipment or products or specified
components or achievement of any results from the equipment,
specified components or services within ranges desired by you
HyPerforma Single-Use Fermentor User’s Guide | 4Thermo Scientific
Warnings, safety, and warranty information
even if those ranges are communicated to us and are described in
specifications, a quote, or a statement of work. ADDITIONALLY, ANY
INSTALLATION, MAINTENANCE, REPAIR, SERVICE, RELOCATION
OR ALTERATION TO OR OF, OR OTHER TAMPERING WITH, THE
EQUIPMENT PERFORMED BY ANY PERSON OR ENTITY OTHER
THAN US WITHOUT OUR PRIOR WRITTEN APPROVAL, OR ANY
USE OF REPLACEMENT PARTS WE HAVE NOT SUPPLIED, WILL
IMMEDIATELY VOID AND CANCEL ALL WARRANTIES WITH
RESPECT TO THE AFFECTED EQUIPMENT. IF THE EQUIPMENT
IS TO BE USED IN THE UNITED STATES, WE MAY VOID YOUR
WARRANTY IF YOU SHIP THE EQUIPMENT OUTSIDE OF THE
UNITED STATES.
Use restrictions
You must use this equipment in accordance with our documentation
and if applicable, with our other associated instructions, including
without limitation, a “research use only” product label or “limited use”
label license. This equipment is intended for research use or further
manufacturing in bioprocessing applications and not for diagnostic
use or direct administration into humans or animals, we do not submit
the equipment for regulatory review by any governmental body or
other organization, and we do not validate the equipment for clinical or
diagnostic use, for safety and effectiveness, or for any other specific
use or application.
HyPerforma Single-Use Fermentor User’s Guide | 5Thermo Scientific
Warnings, safety, and warranty information
Seismic guidance
The buyer of the equipment is responsible for ensuring that countryspecific codes and seismic values are assessed for suitability of
equipment installation and safety at the designated site. In addition,
it is the buyer’s responsibility to assess the building structure for
the designated equipment to ensure correct seismic anchoring and
tethering designs for both the equipment and facility. It is highly
recommended that the buyer consult with a local, licensed third party
architecture and engineering firm to provide the buyer with correct
engineering analysis and stamped documentation prior to equipment
installation at the facility. In addition, the buyer will be responsible for
rigging and anchoring of the equipment to a specified, fixed location.
Upon request, Thermo Fisher Scientific can assist with establishing
compliant seismic anchoring and tethering designs for purchased
equipment based on building and country codes, at an agreed upon
fee.
It is also noted that movable equipment (i.e. non-fixed or caster mount)
is exempt from seismic design requirements according to ASCE
7-16, Chapter 13, section 1.4. Although these units are exempt from
the seismic design requirements of ASCE 7, it should be noted that
such equipment is susceptible to overturning during a seismic event.
Therefore, it is the responsibility of the buyer to address seismic safety
for movable equipment at the designated facility.
HyPerforma Single-Use Fermentor User’s Guide | 6Thermo Scientific
How to use this guide
Rev. Date Section Change made Author
A.0 07/ 2 014 -- Initial release S. Jelus
A 11/ 2 0 16 -- Reformatted E. Hale
A 11/ 2 0 16 3.1.4, 4.2 Updated maximum temperature setpoint J. Brown/E. Hale
A 11/ 2 0 16 3.5.2 Added CPC AseptiQuik connection instructions E. Hale
A 11/ 2 0 16 3.5.5 Removed references to sterility E. Hale
A 11/ 2 0 16 4.2 Updated nominal tip speed E. Hale
A 11/ 2 0 16 Appendix D Added Appendix D (Pre-fermentation run checklist) J. Brown/E. Hale
B 04/2017 4.2
B 04/2017 4.2
B 04/2017 4.4.1
B 05/2017
B 05/2017 2.3, 4.1, 4.6
C 09/2017
C 09/2017 -- Changed values from “psi (bar)” to “bar (psi)” E. Hale
C 09/2017 -- Updated various aspects of formatting E. Hale
C 09/2017
C 09/2017 4.2 Added “Noise level” to specifications table E. Hale
C 11/ 2 0 17 Chapter 4 Removed hardware, BPC part numbers E. Hale
C 01/2018 -- Updated warning symbols E. Hale
How to use this guide
Scope of this publication
This user’s guide contains information about the standard Thermo
Scientific S.U.F. systems, including hardware, components, product
design verification methods, installation, operation, and specifications.
It is intended for use by people who may or may not have experience
with Thermo Scientific systems, but who have some knowledge of
bioproduction processes and large-scale mixing systems.
Document change information
Warnings and
Safety
Warnings, safety,
and warranty
information
How to use this
guide
Added Minimum Ceiling Height Requirement to 30 and 300
L specifications
Replaced “+/- 0.75% of full scale” with “+/- 5 rpm” in Motor
Speed specification field
Corrected part number for standard 30 L BPC with two 5 in.
exhaust filters
Added potentially explosive atmosphere (ATEX) warning E. Hale
Updated 30 L S.U.F. drawings to show the current motor
mount
Added warranty and usage information E. Hale
Added “Abbreviations/acronyms” section E. Hale
E. Hale
E. Hale
E. Hale
E. Hale
HyPerforma Single-Use Fermentor User’s Guide | 7Thermo Scientific
How to use this guide
Rev. Date Section Change made Author
D 11/2 018
D 11/2 018
D 11/2 018 Various Removed references to metal probe clips E. Hale
D 11/2 018 2.2.3
D 11/2 018 3.6.5, 4.6.1 Updated Figures 3.104 and 4.12 E. Hale
D 11/2 018 Appendices Removed Appendix B (AC-Tech calibration) E. Hale
D 11/2 018
D 12 / 2018 3.1.3, 3.6.5 Edited sentence (3.1.3) and reworded step #2 (3.6.5) E. Hale
Warnings, safety,
and warranty
information
How to use this
guide
Warnings, safety,
and warranty
information
Added seismic guidance E. Hale
Changed “Input into Thermo Scientific publications” to
“Questions about this publication”
Updated Figure 2.1, showing the interior of S.U.F. E-Boxes,
and removed Figure 2.2
Added emphasis to “Electrical connections” section E. Hale
E. Hale
E. Hale
D 12 / 2018 4.2
E 10/ 2019 -- Minor revisions T. Golightly
E 10/ 2019 4.2 Updated cart length dimension on Table 4.2 T. Golightly
Warning, safety,
F 06/2020
G 11/2020 --
G 11/2020 4.1.3 Updated Figure 4.5 with new cart dimentions T. Golightly
G 11/2020 4.2
G 11/2020 1.3.1
and warranty
information
Added tolerance (± 5 rpm) to “Motor speed” in
specifications
Added Tipping hazard warning and symbol C. Jones
Minor updates to the document to meet current document
standards
Corrected the overall width, length, height and dry and wet
skid weights in Table 4.2
Updated the "Finesse pH and DO" sensors to "Hamilton pH
and DO" sensors in Table 1.1
E. Hale
T. Golightly
T. Golightly/E. Hale
T. Golightly
Questions about this publication
If you have any questions or concerns about the content of
this publication, please contact technicaldocumentation@
thermofisher.com and your Thermo Fisher Scientific sales team.
HyPerforma Single-Use Fermentor User’s Guide | 8Thermo Scientific
How to use this guide
Related documents
If you are missing any of the related publications listed below, please
contact your local sales representative.
Document Document number
Thermo Scientific HyPerforma S.U.F. Validation Guide DOC0032
Thermo Scientific HyPerforma S.U.F. Packing and Unpacking
Instructions
DOC0052
Abbreviations/acronyms
Refer to the list below for definitions of the abbrieviations and acronyms
used in this publication.
BPC BioProcess Container
DO Dissolved oxygen
ETP Equipment Turnover Package
GFCI Ground fault circuit interrupter
ID Inner diameter
IEC International Electrical Code
OD Outer diameter
PED Pressure Equipment Directive
PID Proportional integral derivative
P/V Power input to volume
rpm Revolutions per minute
RTD Resistance temperature detector
slpm Standard liters per minute
STR Stirred tank reactor
S.U.F. Single-Use Fermentor
TCU Temperature control unit
VFD Variable frequency drive
HyPerforma Single-Use Fermentor User’s Guide | 9Thermo Scientific
Chapter 1 | S.U.F. overview
1
Single-Use Fermentor
(S.U.F.) overview
Chapter contents
1.1 Introduction
1.2 Hardware characteristics
1.3 End user and third-party supplied components
1.4 BioProcess Container characteristics
1.5 Additional system components
HyPerforma Single-Use Fermentor User’s Guide | 10Thermo Scientific
Chapter 1 | S.U.F. overview
1.1. Introduction
The Thermo Scientific Single-Use Fermentor (S.U.F.) has been designed
to be a single-use alternative to conventional stirred tank aerobic
fermentors currently utilized in microbial cell culture applications.
Based on years of accepted stirred tank reactor (STR) design, the
S.U.F. emulates STR scalability and operating parameters, yet it
has the unique advantage of being a single-use device. Ease of
setup with respect to system operation and integration into existing
facilities makes the S.U.F. an attractive alternative to its stainless steel
counterpart. Critical design parameters such as height to diameter
ratios, mixer design and location, and typical control system interfaces
are consistent with traditional fermentation platforms. S.U.F. BioProcess
Containers (BPCs) are supplied sterilized by irradiation and therefore
do not require any facility hook-ups for sterilization or cleaning. A key
element in the single-use design is the plastic (polyethylene) impeller
with a bearing/seal assembly linking to an external mixer drive. Quick
setup and changeover allows for faster turnover in microbial cell culture
runs over traditional reusable systems.
S.U.F. systems consist of the following primary components:
• Outer support container with standard water jacket heating
system
• S.U.F. BioProcess Container (BPC)
• Electrical control panel (E-Box) for agitation
• Direct drive agitation mixing assembly with an AC motor, drive
shaft, and impeller
HyPerforma Single-Use Fermentor User’s Guide | 11Thermo Scientific
Chapter 1 | S.U.F. overview
Figure 1.1. 300 L S.U.F. with electrical
control panel, condenser, cable
management system, and bottle
management system.
The Thermo Scientific S.U.F. utilizes an open architecture design for
the control system, allowing for integration with customer systems
or with third-party controllers for feed pumps, mass flow controls,
and HMI (human-machine interface) screens. Controls for agitation
are integrated into the S.U.F., with temperature, pH/DO probes and
controls being supplied by the user or a third-party integrator. Water
jacketed systems require a temperature control unit (TCU) selected and
supplied by the end user or by Thermo Scientific.
The stainless steel outer support container is engineered and
fabricated to fully support each S.U.F. BPC and allow easy access
for operation. The outer support container is mounted to a portable
cart base and includes the mixing drive, water jacket for heating
and cooling, and optional controllers for mixing. The drive shaft is
detachable and reusable and is inserted into the BPC through the
motor assembly and into the bearing port. Load cells are offered as an
option.
HyPerforma Single-Use Fermentor User’s Guide | 12Thermo Scientific
Chapter 1 | S.U.F. overview
The BPC includes the impeller assembly, sparger, vent filter inlet/outlet
ports, probe integration ports and filling, dispensing, and sampling
ports. The materials are fully qualified for biological product contact
per USP Class VI plastics. Each assembly is manufactured under
cGMP and is supported by qualification and validation information. No
reuse cleaning or sterilization validations are required as the BPC is
provided gamma irradiated. Innovative, proprietary technology allows
for the integration of the mixing shaft, pH and dissolved oxygen (DO)
probes, and the resistance temperature detector (RTD). The probe and
temperature interfaces are comparable to traditional systems with the
design allowing for simple, aseptic connections. Integrated spargers
are built into the S.U.F. BPC through universal ports.
This user’s guide covers the setup, operation, maintenance, and
troubleshooting of 30 and 300 L S.U.F. systems.
HyPerforma Single-Use Fermentor User’s Guide | 13Thermo Scientific
Chapter 1 | S.U.F. overview
1.2. Hardware characteristics
1.2.1. System features
The S.U.F. is designed for system mobility and easy integration while
utilizing a straightforward operator interface. Hardware drawings and
specification tables specific to volume can be found in Chapter 4 of
this guide. The following topics include general descriptions of the
hardware components of the S.U.F.
1.2.2. Agitation
If your system uses a Thermo Scientific electrical control panel (E-Box),
the stirring speed is adjusted by using the keypad interface on the
control panel. The agitation control interface utilizes a digital display
to indicate stirring speed in units of revolution per minute (rpm). Power
is supplied to the motor by a two-position power switch. The up and
down arrows on the agitation keypad adjust the stirring speed. Your
system may also be integrated and managed by a third-party controller.
1.2.3. Control system
The S.U.F. is designed to integrate with existing control systems in
their many configurations. The S.U.F. control system supplied with the
Thermo Scientific E-Box enclosure manages the agitation process
and monitors the pressure inside the BPC. Parameters of pH and DO,
gas management, feed addition, and base addition control must be
managed by an external controller supplied by the end user or a thirdparty integrator.
1.2.4. Exhaust management system
A condenser system is recommended and is available as optional
hardware. It cools exhaust gases and re-circulates the condensate into
the fermentor.
1.2.5. Exhaust vent filter heater
An optional exhaust vent filter heater is available for increased longevity
of the exhaust filter on the S.U.F. BPC. Heating the filter sufficiently
to eliminate the formation of condensation is an effective means of
reducing the risk of fouling of the filter membrane. The heater is factory
preset to operate between 40–55°C, ± 3 degrees. Temperature
settings above 60°C are not recommended.
HyPerforma Single-Use Fermentor User’s Guide | 14Thermo Scientific
Chapter 1 | S.U.F. overview
1.2.6. Temperature
The S.U.F. can be operated within the temperature range from 5–55°C.
The process temperature is measured by means of a supplied RTD
(pt-100) that is inserted into the thermowell of the S.U.F. BPC. Water
jacketed system temperature control is maintained through the TCU or
a third-party controller.
1. 2 .7. Heating performance
Heating times for S.U.F. systems vary based on operating liquid
volume and temperature, ambient or heating fluid temperature, sparge
rate, and mixing rate. Users should adjust process liquid staging
and seeding strategies to the unique aspects of the S.U.F. Process
controllers are designed to provide optimum heat transfer and to
minimize heat up times, while maintaining the material integrity of the
polymer film construction of the S.U.F. BPC. Refer to section 3.1.4 for
expected heating times.
1.2.8. External control
Users can choose to bypass the mixing speed control and display
pressure systems provided with the S.U.F. and utilize existing
controllers. Refer to section 3.6 for more details.
1.2.9. Load cells
Load cells, used to determine the weight of the contents of a S.U.F., are
optional. Load cell kits can be installed at the factory or can be added
later by a certified service technician. The load cell kit comes with three
load cells, summing block, wiring, and display with a choice of several
data interfaces.
Load cells arrive uncalibrated. It is recommended that the load cell
manufacturer or a qualified technician calibrate these systems on site.
HyPerforma Single-Use Fermentor User’s Guide | 15Thermo Scientific
Chapter 1 | S.U.F. overview
Table 1.1. Manufacturers and models of compatible pH/DO probes.
Probe lengths (from O-ring to tip) must not exceed 235 mm (9.25 in.)
1.3. End user and third-party supplied
components
1.3.1. pH and DO probes
The following table shows the length and diameter requirements for
traditional sensors (probes) that can be integrated into the S.U.F. These
requirements are based on the necessary insertion depth of the probe
when used with the probe ports. Note: The presence of a properly
positioned O-ring on the probe is critical for use with the S.U.F.
O-ring to probe tip
Sensor Inserted
Probe Part number Diameter
AppliSens DO Z010023525 12 mm (0.47 in.) 13.5 PG
AppliSens pH Z001023551 12 mm (0.47 in.) 13.5 PG
Mettler Toledo DO
Mettler Toledo pH
Broadley-James DO D140-B220-PT-D9 12 mm (0.47 in.) 13.5 PG
Broadley-James pH F-635-B225-DH 12 mm (0.47 in.) 13.5 PG
Hamilton DO 237542 12 mm (0.47 in.) 13.5 PG
Hamilton pH 238633-2543 12 mm (0.47 in.) 13.5 PG
NOTE: Consult probe manufacturer’s website for appropriate probe cable connection and part number.
InPRO 6800/12/220,
PN 52200966
405-DPAS-SCK8S/225, PN
104054481IG
12 mm (0.47 in.) 13.5 PG
12 mm (0.47 in.) 13.5 PG
Thread
type
Length Length
235 mm
(9.25 in.)
235 mm
(9.25 in.)
215 mm
(8.46 in.)
195 mm
( 7.6 7 in. )
215 mm
(8.46 in.)
225 mm
(8.85 in.)
225 mm
(8.85 in.)
225 mm
(8.85 in.)
235 mm
(9.25 in.)
235 mm
(9.25 in.)
215 mm
(8.46 in.)
219 mm
(8.62 in.)
214 mm
(8.42 in.)
219 mm
(8.62 in.)
220 mm
(8.66 in.)
220 mm
(8.66 in.)
1.3.2. Single-use probes
Mettler Toledo single-use pH and DO sensors are supported, and
BPCs may be ordered with single-use sensors as fully integrated
components.
HyPerforma Single-Use Fermentor User’s Guide | 16Thermo Scientific
Chapter 1 | S.U.F. overview
1.3.3. Controllers
Thermo Scientific operates with an open architecture approach to the
integration of controls. Our industry-leading S.U.F. can be integrated
with most controllers on the market, allowing customers to choose
the control system they want, or to reduce expense by integrating
with a controller that is already onsite. In order to facilitate integration,
electrical schematics are provided in the Equipment Turnover Package
(ETP) supplied with the Thermo Scientific S.U.F.
S.U.F. units may be provided with integrated controls, pump towers, a
control monitor, and advanced features, such as data logging, multiple
S.U.F. connections, and optional 21CFR part 11 compliance for cGMP
manufacturing. A variety of single-use sensors are available for pH,
DO, and pressure control. Thermo Scientific can provide complete,
integrated solutions with the Thermo Scientific OEM Controller, or using
the manufacturers listed below.
• Applikon SUB-Controller
• Legacy Finesse PC Controller
• Emerson Delta V
• Allen-Bradley
• Siemens
Contact your local sales representative for more information.
Note: The S.U.F. will work well with any of the various control system
platforms, such as PLC, PC, DCS, or proprietary operating system
based controllers.
HyPerforma Single-Use Fermentor User’s Guide | 17Thermo Scientific
Chapter 1 | S.U.F. overview
1.4. BPC characteristics
1.4.1. S.U.F. BPC features
The microbial culture itself is contained inside the S.U.F. BPC
(Figures 1.2 and 1.3). The chamber is manufactured from single-web,
multi-layer film, which is a co-extruded structure specifically designed
for biopharmaceutical process usage. All materials are qualified for
a broad range of physical, mechanical, biological, and chemical
compatibility requirements (refer to data in our BPC Catalog, which is
available from your sales representative). The BPC is presterilized using
validated gamma irradiation processes.
1.4.2. Operating pressure
The S.U.F. BPC does not operate as a closed system, as it has both
inlet and exhaust filters that are utilized to maintain an environment for
cells to grow without concern for contamination. However, conditions
can be encountered when gas inlet flow rate may exceed exhaust
flow rate. This may be encountered in the unlikely event of a pressure
regulator failure on a gas feed, or when excessive foaming creates
conditions of vent blockage. The S.U.F. BPC is not rated as a pressure
vessel (gas pressure should not exceed 0.03 bar (0.5 psi) within the
BPC). Custom BPCs can be ordered with an optional single-use
pressure transducer for monitoring the pressure within the S.U.F.
1.4.3. Working volume
Each S.U.F. is designed for a working volume range. The minimum
working volume and the rated working volume are listed in the
specification tables provided in Chapter 4. The total volume listed
includes the head space needed for proper aeration and gas
management. Actual working volumes should not exceed the indicated
rated working volumes. In addition, working volumes less than the
minimums listed can result in damage to the BPC and S.U.F. hardware
malfunction.
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Chapter 1 | S.U.F. overview
1.4.4. Draining and harvest
The S.U.F. is equipped with a bottom drain line that allows for liquid
harvest, typically with a peristaltic pump. Connection of the bottom
drain line can be accomplished by use of a tubing welder or the aseptic
connection of quick connect or fitting that is provided. Manipulation of
the BPC as the last few liters of media are removed can minimize liquid
hold-up within the S.U.F.
1.4.5. Aeration
Gas to liquid mass transfer in microbial culture fermentors is controlled
by the solubility of the gas in the liquid, its distribution, and the
temperature and pressure. Direct air sparging is a way of providing
for the oxygen requirements of cell cultures. The standard S.U.F. BPC
incorporates a unique rind-like film sparger design that allows for
optimal aeration of the culture process.
1.4.6. Aseptic connections
Multiple aseptic connection options exist for S.U.F. users. The
standard BPCs include tubing welder sections, quick connects, CPC
™
AseptiQuik,
or Pall™ Kleenpak™ aseptic connections. The S.U.F.
BPC is designed with various lengths and dimensions of thermoplastic
tubing for the purpose of addition to and dispensing from the S.U.F.
BPC. Refer to ordering information in Chapter 4 for custom end
treatment options.
™
1.4.7. Sampling
The S.U.F. is equipped with a small volume sample port that is adjacent
to the BPC thermowell. This small diameter silicone dip tube of 152.4
mm length (6 in.) allows low void volume samples to be taken for
cell viability and density, as well as analyte analysis. This dip tube is
supplied with an aseptic luer lock connector (SmartSite
for direct sampling or attachment of various sampling manifolds by
use of standard luer lock connection. Alternatively, manifolds can be
™
welded onto the C-Flex
sample line by tubing welder.
™
) that allows
Detailed BPC drawings and standard configuration tables specific to
volume can be found in Chapter 4 of this guide.
HyPerforma Single-Use Fermentor User’s Guide | 19Thermo Scientific
Chapter 1 | S.U.F. overview
1.4.8. BPC features
Figures 1.2 and 1.3 illustrate the components of standard 30 L and
300 L S.U.F. BPCs. See Table 1.2 on the following page for more
information.
1
4
6
11
Figure 1.2. 30 L S.U.F. BPC.
2
3
5
7
9
10
1
2
8
3
6
11
4
5
8
9
7
10
Figure 1.3. 300 L S.U.F. BPC.
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Chapter 1 | S.U.F. overview
Table 1.2. BPC information for Figures 1.2 and 1.3.
1. Exhaust vent filter Single-use capsule filter for exhaust gas exchange (two types available)
2. Condenser bag (optional) Optional single-use condenser bag
Component Description
3. Foam sensor (optional)
4. Seal/bearing assembly
Built-in single-use sensor may be used with a controller to automatically trigger
addition of an anti-foaming agent when excessive foam is present
Links with mixer motor and allows impeller to turn while retaining integrity of
the S.U.F. BPC
5. Feed ports Feed port for addition of media and other liquids
6. Impeller
Injection molded plastic; linked to seal/bearing assembly by C-Flex tubing
contact material of the shaft
7. Ports with single-use sensors
or standard Pall Kleenpak*
Ports with single-use sensors or standard Pall Kleenpak* connectors
connectors
8. Spare sterile connect port Spare port
9. Temperature RTD/ small volume
sampling port
10. Gas sparge line(s)
For integration of temperature probe while retaining integrity of the S.U.F. BPC,
and for needleless sampling or connection to sampling manifold
Drilled hole sparger integrated into the chamber and protected by gas filters
and a check valve (check valve is provided on 30 L units only)
11. Drain port Used when draining the S.U.F.
*CPC AseptiQuik aseptic connectors are also available on S.U.F. BPCs.
HyPerforma Single-Use Fermentor User’s Guide | 21Thermo Scientific
Chapter 1 | S.U.F. overview
1.5. Additional system components
1.5.1. Probe integration
The probe assembly is an innovative design to package user-supplied
pH and DO probes for sterilization and to aseptically connect them to
the S.U.F. BPC. The probe assembly (Figure 1.4) includes the following
components:
1. Molded bellows cover
2. Threaded probe adapter
3. Pall Kleenpak connector (KPCHT series—high temperature)
4. Cable ties
2
Figure 1.4. Probe assembly.
Note: Figure 1.4 shows a Pall Kleenpak connector. CPC AseptiQuik
connectors are also available for S.U.F. systems.
4
1
4
3
1.5.2. Accessories
To assist in the operation of the S.U.F., additional accessories are
available (see accessories below).
Required
• Heavy-duty tubing clamps
Recommended
• Exhaust management system with condenser and vent filters.
Optional
• E-Box
• Sampling manifold with luer lock
• Temperature sample port (for RTD calibration/validation)
• Vent filter heater system—for users who require additional
protection for the exhaust vent filter on the standard S.U.F. BPC;
includes filter heater, controller, and power cord.
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Chapter 1 | S.U.F. overview
• Load cells—Load cell packages include three load cells, summing
block, wiring, and an optional display screen with your choice of
several data interfaces
• Cable management system
• Bottle management system
• Feed bag management hook
See Chapter 4 of this guide for accessory ordering information.
HyPerforma Single-Use Fermentor User’s Guide | 23Thermo Scientific
Chapter 2 | Installation and setup
2
Installation and setup
Chapter contents
2.1 Initial installation preparation
2.2 Installation
HyPerforma Single-Use Fermentor User’s Guide | 24Thermo Scientific
Chapter 2 | Installation and setup
2.1. Initial installation preparation
The Single-Use Fermentor (S.U.F.) hardware will arrive crated. For
unpacking instructions and detailed contents of the crate, please refer
to the S.U.F. Packing and Unpacking Guide (DOC0052).
There will be detailed instructions for crating, uncrating, and assembly
of 30 L and 300 L S.U.F. units. Be sure to follow the instructions
provided and retain all packaging materials. After uncrating, contact
your sales representative immediately if you find that any damage has
occurred in shipping.
2.1.1. Hardware shipment and setup
The S.U.F. hardware will arrive with the following items:
• Outer support container (platform, tank, and control panel)
• Drive shaft, resistance temperature detector (RTD), four probe
brackets, and standard tool set (spanner wrench and torque
wrench)
• Equipment Turnover Package (ETP) provided on a USB drive,
shipped separately
2.2. Site preparation
2.2.1. Electrical connections for units with an electrical
control panel
S.U.F. hardware with AC motors cannot be used on circuits equipped
with GFCI circuit protection due to the potential for nuisance tripping.
The electrical plug on the S.U.F. is a connector that offers a secure
ground. These connectors meet the electrical safety codes for portable
equipment and are International Electrical Code (IEC) rated (meet IEC
standard 60309). This plug serves to provide electrical ground prior
to power connection. The supplied electrical receptacle should be
hard-wired into the facility by a qualified electrical technician; for US
installations the receptacle will require the use of an adapter mounting
plate (supplied) which will fit into a two gang box. For additional
information on the adapter mounting plate, please see the ETP.
Alternatively, the system can be hard-wired directly into the facility.
Note: The yellow plug and receptacle are for 120 VAC and the blue are
for 240 VAC S.U.F.s.
HyPerforma Single-Use Fermentor User’s Guide | 25Thermo Scientific
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