Upstream Processing Solutions
From Research to Production

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

Upstream Process Overview

Solutions for
Upstream Processing Needs
Sartorius offers a wide range of process solutions for cell culture and microbial
production processes, as well as for cell line and process development activities.
SCADA system, process automation and chemometrics toolbox

Media and Media Preparation• Ready-made liquid media
in bottles and bags
• Powder media• Platform system for media
preparation• Prefilters, sterile filters,
mycoplasma-retentive andvirus removal filters• Bags for mixing and storage

Cells and Cell Banking• CHO expression platform• GMP dispensing systems• Cell bank manufacturing andcharacterization

Cell Line andMedia Development• Automated multi-parallel
mini bioreactors• High throughput tools for media
development

Test kits

2

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Production

Clarification• Single-use bioreactors• Single-use centrifugation• Stainless steel bioreactors• Depth filtration• In-line sensors and at-line
analyzers• Sterile filtration• Bulk harvest testing• Virus filtration

Appendix• Crossflow filtration• Membrane chromatography

Process Development• Bags for fluid management(mixing and storage)• Buffers in liquid or powderform• Automated multi-parallel
mini bioreactors• Benchtop bioreactors withglass and single-use vessels• Stainless steel bioreactors• In-line sensors and at-line
analyzers

Tubings, connectors, disconnectors, SU sensors for flow | pressure and valves3

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

Table of Contents

Table of Contents

Introduction

2

Upstream Process Overview
Solutions for Upstream Processing Needs

2
2

Latest Trend powered by Sartorius

6

Cell and Gene Therapy Applications

I. Cell Line8

1. Cell Line Development Services
CellcaCHO Expression Platform
2. Cell Bank Manufacturing and Characterization
An Integrated Cell Banking and Characterization Package
Closed Cell Bank Manufacturing System
3. Automatic Dispensing of Banks, Samples and Standards

10
10
12
12
14
16

II. Media

18

1. Cell Culture Media
Experience and Flexibilityfor Cell Culture Needs
Media Services
2. Media Preparation
Solutions for Media Preparation
3. Media Sterile Filtration
Filter Selection Guide

20
20
24
26
26
30
30

III. Bioreactors and PAT

34

1. Overview

36
36
38
49
54
61
62
64
66
68
68
70
71

Which Bioreactor Fits Your Needs?
2. Mini Bioreactors
3. Benchtop Bioreactors
4. Single-Use Bioreactors
Holistic Safety Concept of BIOSTAT STR®
Flexsafe® Bag Family
Rely on Proven Scalability – Accelerate The Development
5. Stainless Steel Bioreactors
6. Bioreactor Control
Gas Supply Options
Oxygen Control Strategies
Advanced Measurement and Control Loops

4

6

Sub chapter | Feature Pages

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

7. Process Analytical Technologies
Sartorius Process Analytical Technologies
8. Process Analyzers and Sensors
Automated Cell Bleed in Intensified Processes Through BioPAT® ViaMass
9. Process Automation
Automation is Key
Seamless Scalablity and Data Consistency with BioPAT® MFCS
Software Modules BioPAT® MFCS
10. Chemometrics
Umetrics® Chemometrics Toolbox
11. Training Software
12. Instrument Services

72
72
74
75
82
82
85
86
87
87
93
94

IV. Clarification

96

1. Automated Cell Removal | Supernatant Clarification
2. Cell and Contaminant Removal with Depth Filters
3. Centrifugation Systems

98
99
100

V. Bioanalytics and Biosafety102

1. Product Characterization and Biosafety Testing Services
Physicochemical and Biological Analytical Comparability for Biosimilars
2. Bioanalytics
3. Virus Quantification

104
104
110
111

VI. Application and Engineering Services

112

1. Integrated Process Development Services
Accelerate The Early Phase Drug Development
2. Bioprocess Development & Engineering
Flexible, Scalable and Cost Efficient Bioprocess Facility Solutions
3. Application Centers
Visit Your Closest Sartorius Application Center!

114
114
116
116
118
118

Appendix

120

Glossary

120
122
124

Solutions for Downstream Processing Needs
Overview Weblinks

Appendix5

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

Latest Trend powered by Sartorius

Cell and Gene Therapy
Applications
Developers and manufacturers of cell and gene therapies require technologies and solutions
with assured process integrity and a robust supply chain, which are critical to the successful
development and manufacturing of these advanced therapies.
Sartorius is a global solution provider for the biologics industry, especially for antibody andvaccine production. Knowledge and experience gained with these proven products and services
provide a strong foundation to support upstream and downstream processing of cells andviruses for allogeneic and autologous advanced therapies.
Therapy development can benefit from our single use systems, intelligent equipment andprocess analytical tools enabling accelerated process development and realization of therapy
production goals. .
Highlighted here are some upstream solutions for research, process development andoptimization, and production workflows for autologous and allogeneic advanced therapies:• Cellular Immunotherapy
Sartorius provides the cellular immunotherapy industry with a range of scalable
single-use production technologies. Our
portfolio supports immune cell expansion,
viral vector production cell expansion, anddownstream processing steps.
• Gene Therapy and Viral Vectors
Viral vectors such as adenoviruses,
adenoassociated viruses, lentiviruses andretroviruses are effective delivery systems
for genetic material used in cell and genetherapies. Sartorius technologies are ideallysuited for development and manufacturing
processes for viral vectors. They allow
end-to-end, single-use processing of virus
batches at scales required for processdevelopment through to commercial
manufacturing, up to 2,000L.

6•	Cell Therapy
Cell therapies applications encompass theuse of various types of stem cells
such as mesenchymal stem cells (MSCs) or
induced pluripotent stem cells (iPSC).
MSCs are the most commonly used class ofmultipotent stem cells and are illustrativeof production requirements of other celltherapies. Sartorius' portfolio of technologies supports scalable cell expansion anddownstream processing steps including
harvest, wash, and concentration of cells.

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

AppendixTechnology Options Include
Stage ofDevelopment

Step

Cellular Immunotherapies

Viral Vectors for Cell & Gene
Therapies

Cell Therapies

Researchand Process
Development

Expansion• ambr® 15• ambr® 250• ambr® 15 & ambr® 250• Umetrics® MODDE®
• UniVessel® Glass• UniVessel® SU• ambr® 15 &ambr® 250 modular• UniVessel® Glass• UniVessel® SU

Production

Media Preparation• Flexsafe® 2D Bags
• Single-use mixing systems• Sartorius Filter range• Single-use mixing systems• Flexel® & Flexsafe® &Flexboy® Bags
• Palletanks• Sartorius Filter range• Single-use mixing systems• Flexel® & Flexsafe® &Flexboy® Bags
• Palletanks• Sartorius Filter range

Expansion• BIOSTAT ® RM TX &
BIOSTAT ® B Control Unit
• BioPAT ® MFCS
• Flexsafe® RM TX Bags &BioPAT ® ViaMass• BIOSTAT ® RM or STR®
• BIOSTAT ® B Control Unit
• BioPAT ® MFCS

• BIOSTAT ® RM
• BIOSTAT STR®
• BIOSTAT ® B Control Unit
• BioPAT ® MFCS

Please ask a Sartorius specialist for more information
about the portfolio for any stage of individual process.
Contact us on
regenmed@sartorius.com
7Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

﻿

I. Cell Line8

1. Cell Line Development Services

10

2. Cell Bank Manufacturing and Characterization

12

3. Automatic Dispensing of Banks, Samples and Standards

16III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix9

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

1. Cell Line Development Services

Cell Line Development
Services
CellcaCHO Expression Platform
Sartorius Stedim Cellca is a leading provider of Cell Line Development Services for large-scaleprotein production of biopharmaceuticals in mammalian cells. Within 4 months the CellcaCHO
Expression Platform can provide a stable well characterized Research Cell Bank (RCB)
with titres consistently exceeding 3g/L in an easily scalable fed-batch process.

CellcaCHO Expression Platform
Host Cell Line•	CHO DG44
•	Growth in suspension•	Long-term stability•	Fully documented history

Media System•	Chemically defined•	Free of animal components•	Free of proteins & peptones•	Optimized for Cellca cell lines

Expression Vector•	DHFR system with highselection stringency without
any MTX | MSX, antibiotics•	Optimal signal peptide•	Freedom to operate

Upstream Process Design•	Robust•	Easy to scale•	Proven performance invarious bioreactor systems

Key Benefits
Speed•	From DNA to high-titre RCB in 4 months.
Save up to 3 months by omitting the needfor scalability studies.
Track Record•	More than 90 successfully completed projects.
Scalability•	Processes can be easily transferred andscaled-up to a range of bioreactors.

VectorCloning

Transfection and
Pool Generation

Performance•	Up to 8 g/L in a ready-to use, unoptimized
12 – 14 day standard fed-batch process.
Customer Focus•	Committed project teams and dedicatedclient managers deliver service excellence
and meet our clients requirements.

Single Cell
Cloning

Clone
Evaluation

From DNA to RCB in 4 Months

10

RCB
Preparation

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Products•	mAbs (IgG1, IgG4, IgG2)•	Fusion proteins•	Fab-related products•	Bispecifics•	Biosimilars

Scalability & Robustness - High Titer & Viability, Low Lactate Levels

Scalability and Robustness – High Titer & Viability, Low Lactate Levels
2000 L

4,0

Titer

Viable cell concentration

250

VCC [105 cells/mL]
Viability [%]200 L

UniVessel® Glass 5 L

UniVessel® Glass 5 L

3,3

200

2,7

150

2,0

Viability100

1,3

Lactate50

Titer, Lactate [g/L]

5L

300

BIOSTAT STR® 200 L
BIOSTAT STR® 200 L

0,7

BIOSTAT STR® 2000 L
0

0,0
0

2

4

6

8

10

12

Time [d]BIOSTAT STR® 2000 L

1Scalability from shake flask to 1000 L with minimal process development

Cell Line Development: Track Record
2 g/L

3 g/L

4 g/L

5 g/L

6 g/L

7 g/L

8 g/L

Pre-clinic & Phase 1

16

29

20

12

8

1

1

Phase 2

1

–

1

–

1

–

–

Phase 3

–

1

–

1

–

–

–

Market Approval

1

–

–

–

–

–

–

Un-optimized yields in a 12-14 fed-batch process with minimum 70% viability

Stability
Study

Bioreactor
Confirmation

Transfer &Documentation3 – 4 Months

11

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Cell Bank Manufacturing and Characterization

Cell Bank Manufacturing
and Characterization
An Integrated Cell Banking andCharacterization Package

To ensure safety and quality of any biological product, it is essential to have a fully characterized,
well-documented, homogeneous, Master Cell Bank (MCB) and Working Cell Bank (WCB).
The Cell Line and Testing Solutions portfolio now offers fully GMP cell bank manufacturing
as well as cell bank characterization.
Cell Bank Manufacturing• Closed, single-use manufacturing system with in line monitoring and control• Dedicated facility to mammalian suspension cells, no serum or animal products,
no bacteria or viral products• Up to 500 vial cell banks at 1– 3 +107 cells per vial
• Automatic vial filling system and controlled rate cryopreservation• Storage of filled vials in vapor phase LN2

From RCB to Released MCB in 5 months
Cell Bank Manufacturing
500 vials

Cell Bank Characterization
5 months

12

ReleaseII. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

13

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

2. Cell Bank Manufacturing and Characterization

Cell Bank Manufacturing
and Characterization
Closed Cell Bank Manufacturing System

Cell Bank Manufacturing Process Flow

Initial cellrecovery in
Grade A system

14

Serial expansion
in closed system

Asepticconnections via
sterile welding

Cell harvest,
concentration,
centrifugation

Automatedfilling:
500 vials within
20 minutes

Controlledrate freezing;
harvest to
storage under2 hours

III. Bioreactors and PAT

IV. Clarification

Ultimate Safety
Standards• Closed & automatedsystem• Automated filling(fill-it)• Dedicated facility
for mammalian,suspension cell banks
using serum-free &animal component
free media• Extensive environmental monitoring
programme• Manufacturing
process brothqualified for sterility
assurance

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Regulatory Acceptance

Deliverables• MHRA IMP(MIA) licenced
manufacturing
facility• MHRA GMP Licenced
Testing Facility• Facilities andequipment validated
to VMP• Cell bank testing
to global regulatory
standards• > 500 vial bank ~1 × 107 viable cells
per vial• Manufacturing
Summary Report• Certificate of GMP
Compliance• TSE | BSE Batch
Certification• Certificate ofAnalysis for each
Release andCharacterization
Assay

Appendix

Integrated Approach: DNA to Cell Bank Release
The Cell Bank Manufacturing Services can be easily combined with our Cell Line Development
Services and Cell Bank Characterization Services for a de-risked and time-saving approachfrom DNA to MCB in 10 months.

From DNA to MCB in 10 Months
DNA Synthesis

Vector Cloning &Pool Generation

Single Cell
Cloning & Clone
Evaluation

RCB Generation& Testing

MCB
Manufacturing

MCB
Characterization

MCB Release

10 months

15

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Automatic Dispensing of Banks, Samples and Standards

fill-it
Automated Cell and Strain Banking System

Applications• GMP cell banking• Cell banking for discovery
purposes• Strain banking under GMP
and non-GMP requirements• GMP liquid aliquotation

fill-it is an automated benchtop system for creating high-quality cell and strain banks
in cryovials.
The system works with racks of branded
0.5 – 5.0 mL cryovials in 24-way, 48-way and
96-way formats.

or other downstream activities. It is a provensystem designed for easy installation ona laboratory bench or in a standard biosafetycabinet.

The fill-it system decaps all cryovials
simultaneously and then dispenses cells,strains or liquids into the cryovials before
recapping, ready for transfer to freezers

16

High-throughput system unlike slow manual
processing

k Permits processing of large batches, significantly
reducing QC costs and increasing productivity

Automated dispense module with peristaltic pump
and an aseptic single-use tube set certified forcompliance with GMP

k High-throughput aseptic transfer of cell, strains andliquids improves product consistency and reduces therisk of contamination

Validatable IQ | OQ processes for GMP

k Supports clinical development, regulatory approvaland manufacture of biologics

System has a simple three-button user interface
and fits on a laboratory bench or in a standard
biosafety cabinet

k Easy-to-use flexible system with small footprint
designed to fit in any laboratory

Automated decap | recap module

k Reduces risk of repetitive strain injury comparedwith manual processing

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

AppendixIntroduction

Table of Contents

Latest Trend powered by Sartorius

II. Media

I. Cell Line﻿II. Media

18

1. Cell Culture Media20

2. Media Preparation

26

3. Media Sterile Filtration30

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

19

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

1. Cell Culture Media

Experience and Flexibility
for Cell Culture Needs
Development of powerful cell culture media and feed strategies has dramatically changed
the way of producing antibodies, recombinant proteins and vaccines. Today, antibody titers of
up to 10 g/L and beyond can be achieved in intensified cultures using serum- or protein-freeor even chemically defined media and feeds.
Sartorius offers a broad range of powerful cell culture media for the most common cell lines
used for protein and virus production.
As selection and optimization is cell line dependent and a critical aspect of processdevelopment, we provide qualified application support and development services
to our customers.

The cell culture platform media offering includes• Serum-free media• Protein-free media• Animal-origin-free media• Chemically defined media• No virus or prion concerns• Simplified downstream processing• Maximized yields

Experience and Quality

Flexibility and Customization•	Rely on a partner who understands
the criticality of an appropriate quality
system, quality control and assuranceof supply.
•	All raw materials are selected to comply
with European and U.S. Pharmacopeia
standards. If available, they are froma certified non-animal origin source.
•	Powder media are produced in a controlledarea at low humidity to prevent any
inadvertent hydration. All liquid media
are made from water for injection forthe best microbiological quality.

Sartorius as partner can help to adapt cell
culture media formulation to specific needs.
•	Liquid media in containers ranging from
0.5 L bottles to 1,000 L bags; up to 10,000 L
per batch•	Powder media in package sizes of up
to 20 kg per unit; up to 7 tons per batch
Come to the right place to optimize yourcell culture medium.
• Expert support for your media optimization• Media optimization services
The Sartorius Media Team is looking forward
to supporting customer specific projects inmaking it a success.

20

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix• Long-term relationships with dualsourced raw material suppliers
guarantees supply and quality• Leading position in single-use
applications that include fluid
management, filtration andprocess analytical technology• Pioneer in state-of-the-art
micronization high-quality powder production processes

Industry with
Cell Culture Media
Solutions• Risk minimization approach
applied to powder | liquid solutions• ISO certification with successful audit
track record following Current Good
Manufacturing Practices 21CFR820

Complete Solution
All liquid media filtered through Sartorius filters;
full media qualification package and support

k Optimized media filtration and guaranteed successful
scale-up and transfer into commercial production

Pre-weighed buffer and media powder
in ready-to-use dispensing bags

k Simple and straightforward media and buffer
preparation with Sartorius FlexAct® MP or mixing
solutions

Advanced feeding and control strategies using
Sartorius ambr® and BIOSTAT ® ­bioreactors,
sensors, MFCS supervisory ­control system andchemometrics tool box

k Fast track to optimized culture conditions and yields

Sartorius one-stop shop for integrated and optimized k Full process support allows you to focus on customer
core tasks and targets
solutions for cell line, media and process development
and production of cell culture derived products

For more information please contact:
CellCultureMedia.EU@Sartorius.com (for EU and Asia)
CellCultureMedia.NA@Sartorius.com (for Americas)
Info_CellCultureMedia@Sartorius.com
21

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

1. Cell Culture Media

Broad Range ofCell Culture MediaMedia Are Available as Liquid and Powder
for Maximun Flexibility

Applications• Mammalien and insect cell
culture• Process developpment andoptimization• Media preparation can beused with WFI-quality waterin bags

With maximun flexibility different format can be provided. For media preparation,
WFI quality water in bags can be used.
Cells
CHO (e.g., DG44, CHO-S, CHO K1, DHFR–)

Hybridoma
NS0
Insect cells (e.g., Sf9, Hi 5)
Vero

Primary Application
Proteins

Adherent

Proteins
Proteins
Proteins | Vaccines
Vaccines

MDCK

Adherent

Vaccines

HEK 293

Adherent
Suspension

Vaccines

Per.C6® *Mesenchymal stem cells
Adult dermal fibroblasts
Adult and neonatal primary keratinocytes
hPSC and IPSCs* License required

22

CultureSuspension and adherent
Suspension
Suspension
Suspension
Suspension

Adherent
Adherent
Adherent
Adherent

Vaccines
Cell therapy
Cell therapy
Cell therapy
Cell therapy

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

1. Cell Culture Media

Custom Media Formulations
Adapted Solutions for Customer Requirements

Applications• Vaccine production• Therapeutic protein
production• Cell therapy

In addition to off-the-shelf media formulations, we support our customers with the
manufacture of their own proprietary media formulation, either in liquid or powder
format. The team of experienced media specialists can also assist with the development
and optimization of cell line specific medium and feed formulations. Get a support
about cell line and process development to clinical and commercial production.
Media Optimization Services and Support
The media specialists will develop or
optimize customer specific media formulations
designed for your unique cell culture
requirements.

Media Supply for GMP Production
The media production facilities are
ISO 9001 | 2008 and 13485:2012 compliant
following cGMP 21CFR820 guidelines.

Media Supply for Process Development
An expedited production option for thosethat require high quality cell culture media
for process development and non-GMP
production.
Homogeneous particle size of powder formulations

k Reduces regulatory burden
k Facilitated dissolution

Two redundant manufacturing sites

k Security of supply globally

Wide range of batch sizes and packaging• Up to 10,000 L for liquid formulations• Up to seven tons for powder formulations

k Excellent partner for scale-up, matching needsfrom preclinical to commercial phase

Similar offering for buffers

k Products also for downstream processing

23

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

1. Cell Culture MediaMedia Services
In addition to a broad standard classical and chemical-defined portfolio,
Sartorius media services team is able to provide custom cell culture solutions.

Quality
Sartorius is currently engaged in the
manufacture of over 1,500 products for pharmaceutical and biotechnology applications
such as disease diagnosis, biomedical research,
production of diagnostics and therapeutics
as well as quality control testing of pharmaceuticals and medical devices for the presenceof bacterial contaminants.
Manufacture of these Sartorius products –specifically cell culture media, reagents, andbuffers – follow the protocols and compliancespecifications of the following industry
regulations:• 21CFR820• ISO 9001: 2008 certified• ISO 13485: 2003 certified

In order to maintain consistent quality
in sterile cell culture media products, strict
control of each production lot is essential.
Written procedures in accordance withcurrent Good Manufacturing Practice (cGMP)
provide quality control from start to finish
for each product.
To verify the conformity of material toestablished specification throughout the
manufacturing process, inspections andtesting are carried out during these fourstages:• Raw material receipt• In-process manufacturing, labeling andpackaging• Finished product• Post-manufacture for shelf life studies

Media Processes

Customization

Support andValidation

Quality
Packaging
and Shipping

24

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Packaging
Sartorius' business units are industry-leading suppliers for the application they serve, such as
filtration, fluid handling and fermentation. Combining forces enhances the strength ofSartorius Stedim Biotech. With decades of experience and a rich heritage in engineering, thepackaging solutions will be answering the customer specific needs providing excellence in customer service, product quality and innovation solutions.
Sartorius wants to protect our products in the best possible way with high-quality packaging –on the inside as well as the outside. There is a particular value on the highest standards ofsafety and security, in order to offer efficient and flexible solutions in a market that is bothchallenging and constantly changing.

Shipping
Media & Buffer product storage and shipping conditions vary. While some can be stored
at ambient temperature (uncontrolled), others might need to be stored at room temperature(15 – 30°C), refrigerated (2 – 8°C) or frozen (–10°C | –20°C). Appropriate packaging is provided
to maintain optimal conditions during shipping. We have years of experience in shippinga broad range of volumes of our products (in liquid or powder form) at different temperatures
all around the globe. Custom transportation solutions can be tailored to every specific need
if required.

Shipping Solutions for Media & Buffers | Powder Form
10 g to 2 kg
Bucket5 kg to 20 kg

2 kg to 20 kg

500 g to 2 kg

•

Drum

•

Powder Bag•

Flexel Tankliner•

Shipping Solutions for Media & Buffers | Liquid Form
BottleLDPE 2D Pillow Bag
Drum

0.5 to 1 L

1 to 2.5 L•••

2 to 20 L

50 L

100 L

200 L

•

500 L

1000 L•••LDPE 3D Bag inContainer

•

•

•

•

Stainless Steel
Palletank

•

•

•

•

•

•

Plastic Palletank25

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Media Preparation

Solutions forMedia Preparation
Sartorius offers:• A broad portfolio of filtersfor various media types,­including chemically definedor protein, serum or­hydrolyzate-supplemented• Safe solutions for­mycoplasma risk mitigation;
combining high retention
efficiency with optimalthroughput for costeffective processing

Cell culture media are produced in large volumes and aseptically transferred into bioreactors.
Key process steps involved in media preparation are the mixing of the powder media with water
for injection (WFI), sterilizing-grade and mycoplasma-retentive filtration and media storage­before use.
Continuous cost pressure, increased titers and reduced production volumes have led to theadoption of single-use technologies – both for bioreactors and media preparation. Sartorius has
therefore developed the fully automated, easy-to-use FlexAct® MP system that helps reduce­labor intensive steps to ensure higher productivity.
As leading partner for upstream processing, Sartorius provides integrated s­ olutions thatcomprise cell culture media, bags, sterilizing grade filters, mycoplasma retentive filters andvirus risk mitigation technologies.

• Prefilter portfolio with
optimal protection of final
filters to further reduce
filtration costs• All media filtration solutions
are available both for singleuse processing and media
production in stainless steel
equipment• Industry leading systemdesign with highest total
throughput and economic
filtration

SterilizingGrade Filters
MycoplasmaRetentive­Filters

Automated
Media­Preparation
Cell
culturemedia
Storage Bags

Virus
Removal­Filters

Mixing Bags

Media Filtration Solutions
The choice of an appropriate filtration
solution for media preparation highly depends
on the composition of the cell culture medium.
Often, 0.2 µm-rated sterilizing-grade filters
are used for media preparation. However,reports of mycoplasma contamination of cell
culture processes have put 0.1 µm-rated
mycoplasma-retentive filters into the spotlight,
again. Typical sources for mycoplasma
contamination are animal-derived materials,
such as trypsin or serum; plant-derived
culture media supplements, such as soy-based
26

supplements; and contamination causedby the operators themselves. Producers of cell
culture media have to assess their potential
risk for mycoplasma contamination in orderto decide which filtration method to use.
Sartorius media filtration solutions range
from prefilters to sterilizing-grade andmycoplasma-retentive filters – tailored to thespecific filtration needs of the various typesof cell culture media.

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Single-Use Media Preparation
Today, single-use systems for media preparation
are available up to 3,000 L volume. Whileusers initially converted individual production
components to single use, the industry is
now moving towards completely integrated
systems for media preparation.
The Sartorius FlexAct® MP media preparation
platform is a highly automated, fully closed
system: It starts with powder dissolution ina single-use mixing system, which is followed
by sterile filtration and the transfer of theready-to-use media into a storage bag. To
avoid errors, the entire media preparation
process is supervised by a multi-functional
central control unit. It monitors and records
all relevant process data, such as operatingpressure, pH, pump speed and fluid level.
Sartorius filters and single-use bags are­supported by an industry-leading documentation package, which includes validation andextractables guides. The Sartorius validation
experts support customer throughout qualification of single-use systems for biopharmaceutical production.
• Complete range of single-use bags formedia preparation, mixing and storage
from 50 L up to 3,000 L• Magnetic mixing technology with universal
mobile drive unit
• Fully integrated FlexAct® MP media­preparation platform• Comprehensive validation support
for extractables | leachables by our­dedicated validation teamPowder media

MixingVirus Risk Mitigation inMedia Preparation
Virus risk mitigation in cell culture media
preparation is a hot topic. Multiple bioreactor
contaminations reported over the past
several years have been caused by small,non-enveloped viruses like MVM and Vesivirus
derived from raw materials.
Technologies such as high-temperature,­short-time (HTST) treatment and virus removal
filtration have been employed for virus risk
mitigation in cell culture media preparation.
The new Virosart® Media filter is a uniquesolution for cost effective risk mitigation. It
combines highest flux with superior capacity
and is the method of choice for chemicallydefined cell culture media.
• Cost effective virus risk mitigation ofchemically defined media with the new
Virosart® Media• Orthogonal and robust technologies for
effective contamination control

Filtration

Storage27

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Media Preparation

FlexAct®
Single-Use Solution
for Automated Media Preparation

Learn more about
®
Learn
about
Solution
FlexActmore®
Solution
FlexAct
Overview Weblinks 124

Applications• Sterile Media Preparation• Virus Mitigated Media
Preparation

The FlexAct® configured to order solution brings together
hardware, software, wetware and documentation intoa ready to use package for single-use bioprocessing.

28

Media preparation can be configured within
the offered application space making it capableof preparing single or up to 10 aliquots ofmedia in 2D and 3D single-use bags. It uses
pre-defined configurable software based on
ANSI | ISA-S88 industrial standards for batchprocessing.

The software architecture allows easy interface to Distributed Control Systems (DCS) for
plant-wide integration. The modular FlexAct®
build and connection of sensor, actuator andholder components allows them to be shared
between unit operations, enabling a single
FlexAct® system to perform up to 6 distinct
unit operations at various volumetric scales.

Flexible processing skids with multiple functionality
for diverse unit operations

k Supports multi-product | adaptive-scale bioproduction

Easy to integrate into distributed control systems
and manufacturing execution systems

k Speed and effort of system integration

Easy-to-use predefined application software
based on flexible unit operation recipes

k No additional coding or programing of software

Reliable Single-Use sensor and actuator technologies

k Higher process accuracy and control

High degree of automation, user guidance,system diagnostic and process transparencyk A reduced risk of error and unplanned downtime

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

AppendixIntroduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Media Sterile Filtration

Filter Selection Guide
Learn more
more about
about thetheLearn
2 Filter
Filter Family
FamilySartopore®® 2
Sartopore
Overview Weblinks

124

Todays industrial cell culture media formulations can be very different spanning, from serumand hydrolysate supplemented to chemically defined media. Sartorius has a long standing
experience in media filtration. Based on this there are recommended filter solutions for eachneed. The international team of application specialists helps to optimize the customer’s
specific filtration process. Get in contact with Sartorius today.

Learn more about the
Learn more about theSartoguard Filter Family
Sartoguard Filter Family
Overview Weblinks

124

Media Type
Serum, soy or yeast
hydrolysate-supplemented
cell culture media

Chemically definedcell culture media

Complex serum-free media

Sterile Filtrate Required
Recommended Prefilter
Sartoguard GF
1.2 µm | 0.2 µm

Sartoguard PES
1.2 µm | 0.2 µm

Sartoguard PES
1.2 µm | 0.2 µm

Recommended Final Filter
Sartopore® 2 XLG
0.8 µm | 0.2 µm

Mycoplasma Removal Required
Recommended Prefilter
Sartoguard GF
0.8 µm | 0.1 µm

Sartoguard PES
0.8 µm | 0.1 µm

Recommended Final Filter
Sartopore® 2 XLM
0.2 µm | 0.1 µm

Virus Removal Required
Recommended Prefilter
Sartopore® 2 XLM
0.2 µm | 0.1 µm

Recommended Final Filter
30

Virosart® Media
20 nm

Sartoguard PES
0.8 µm | 0.1 µm

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

3. Media Sterile Filtration

MaxiCaps® MR
Unique Large Scale Single-use Solution

Learn more about®
MR
the MaxiCaps
Learn
more about®
theMaxiCaps
Overview Weblinks MR
124

Applications•	Media & Feeds Filtration•	Large-Scale Buffer
Preparation•	Post Cell Removal Bioburden
Reduction for mAb's•	Clarification of Viral Vectors& Gene Therapy Products

Pre-assembled, pre-sterilized and self-contained: MaxiCaps® MR is designed for large-scale
filtration in biopharmaceutical applications. It maximizes filtration capacity and minimizes risk.
Single-use filter capsules have beensystematically replacing stainless steel filter
housings and cartridges as an highly economical choice for the biopharmaceutical industry.
From capsules to complex custom assemblies,
the implementation of single-use filter
assemblies provides shortened setup times
and hardly any clean up time.

MaxiCaps® MR offers a single-use,large scale-filter system which can be
configured with a filtration area between
5m2 to 27m2 and high quality Sartorius
brand filters. Within the upstream process
it is used for Media & Buffer Preparation,
Cell Removal and Clarification applications.

90% less tubing

k Better handling and small footprint

90% less connections

k Highest safety

No assembly required

k Easy installation

Pre-sterilized systemk Ready-to-use

One integrity test only

k Saves up to 4 hours

31

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Media Sterile Filtration

Sartocheck® 5 Plus
Filter Integrity Tester
Keeps Risk Factors Under
Complete Control

Learn more about®
5 Plusthe SartocheckLearn
more about
FilterIntegrity ®Tester
5 PlustheSartocheck
FilterIntegrity
TesterOverview Weblinks 124

Applications• Integrity testing of filters
pre and post use

The Sartocheck® 5 Plus perfectly meets today's key industry requirements for filter integrity
testing in demanding GMP enviroments.
It sets a new standard for filter integrity
testing devices:• Surpass the Requirements of Quality Risk
Management (QRM)

32• Reach the Ultimate Level of Data Integrity• Experience the Comfort of Intuitive Usability• Discover the Simplicity of Health, Safety,
and Environment (HSE)

Quality Risk Managementk Specific program parameters allowing detectionof user errors and abnormal test conditions.

Data Integrityk Flexible user matrix for generating individual roles,
double data back up and a barcode scanner function.

Highest Safety for Operator, Drug & Environment

k The Sartocheck® 5 Plus is the only ex-proof integrity
tester device on the market. This provides safety when
testing alcohol wetted filters.

Usability

k Automatic test time for faster testing as well as
attractive and intuitive industry rewarded userinterface (iF Design Award 2018).

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

3. Media Sterile Filtration

Virosart® MediaFirst Virus Retentive Filter for
Cell Culture Media

Learn more about
the
virus
riskabout
mitigation
Learn
more
strategythevirus risk mitigation
strategy
Overview Weblinks 124

Applications•	Media preparation ofchemically defined cell
culture media• Addition of media feeds
such as glucose

Virus-retentive filtration is a highly effective method for viral risk mitigation of cell culture
media. Virosart® Media filter provides more than 4 LRV (log10 reduction value) for small
non-enveloped viruses and more than 6 LRV for larger enveloped viruses.
This media filter provides a cost effective
solution with highest filter capacity forcell culture media.

Through this high capacity it overcomes
today's bottlenecks of virus filters originallydeveloped for downstream applications.

> 4 LRV for small non-enveloped viruses> 6 LRV for large enveloped virusesk Highest safety for cell culture

New high-performance PES membranes

k Highest capacities and flow rates
No impact on cell culture performance

Capsules and filter transfer sets delivered gamma
irradiatedk Ready-to-use
Easy implementation into single-use processes

33Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

﻿III. B ioreactors and PAT

34

1. Overview

36

2. Mini Bioreactors

38

3. Benchtop Bioreactors

49

4. Single-Use Bioreactors

54

5. Stainless Steel Bioreactors

66

6. Bioreactor Control

68

7. Process Analytical Technologies

72

8. Process Analyzers and Sensors

74

9. Process Automation

84

10. Chemometrics

87

11. Training Software93

12. Instrument Services

94III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix﻿35

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

1. Overview

Which Bioreactor Fits Your Needs?
Available for
Cell Culture (CC)or Microbial (MO)CultureScreening ofMedia, Clones
or Expression
Constructs

Small-Scale
Protein
SupplyCC

Process
Development
Optimization,
Characterization

Seed Expansion

Production
Product( )ambr® 15 cell culture
Generation 2

MO
CC
MO

ambr® 15 fermentation

CC

( )

MO

( )

CC

( )

MO

( )

ambr® 250high throughput
ambr® 250 modular

CC

( )

( )

MO

( )

( )

BIOSTAT ® A

CC
MO

BIOSTAT ® B

CC
MO

BIOSTAT ® B-DCU

CC

( )

MO

( )

( )

BIOSTAT ® Cplus

CC
MO

BIOSTAT ® D-DCU

CC
MO

( )

( )

( )

BIOSTAT ® RM

CC
MO

BIOSTAT ®® RM TX

CC
MO

( )

( )

( )

( )

BIOSTAT STR®

BIOSTAT ® A

BIOSTAT ® B

Typical applications( ) Selected applications

ambr® 15 cell culture
Generation 2

36ambr® 15
fermentationambr® 250 modularambr® 250high throughput

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Cultivation Chamber Type
Product
Single-Use

Glass

Stainless Steelh®

ambr 15 cell culture
Generation 2hambr®® 15
15 fermentation
fermentationambr

hambr® 250high throughputhambr® 250 modular

h

h

h

h
h

BIOSTAT ® Ahhh

BIOSTAT ® Bhhh

BIOSTAT® B-DCUhh

BIOSTAT ® Cplushh

BIOSTAT ® D-DCUh    h *

BIOSTAT ® RM

hNumberof Parallel
Vessels

Appendix

Max. Vessel
Working Volume

24 | 48

10 –15 mL24

8 –12 mL

12 | 24

100 – 250 mL

2|4|6|8100 – 250 mL

1

1– 5 L2

1–10 L6

1–10 L1

5 – 30 L

2

10 – 200 L

2*

0.5 –100 L

2

0.5 – 5 L

2**

50 – 2,000 L

BIOSTAT ®® RM TXh    h *

BIOSTAT STR®

h Available
h * Available for low cell density applications

BIOSTAT ® B-DCU

BIOSTAT® Cplus

BIOSTAT ® D-DCU

BIOSTAT ® RM

* Twin versions available for RM Rocker 20 L and 50 L** Twin versions available for BIOSTAT STR® 50 L and 200 L

BIOSTAT ® RM TX

BIOSTAT STR®

37

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Mini Bioreactors

ambr® 15 cell culture
Generation 2
Advanced Microbioreactor System
for Cell Culture Applications
Learn more about
Learn
more
about ofthe new
generation
®
the
new
15generation
cell cultureof
ambr®
cell culture
ambr
Overview15
Weblinks
124

Applications
Clone selection
Media and feed development
Early process optimization
Perfusion mimic processes
DOE studies

•
•
•
•
•

ambr® 15 cell culture is an automated, high throughput microbioreactor system that monitorsand controls 24 or 48 cultures in parallel with working volumes from 10 – 15 mL.
ambr® 15 cell culture replicates laboratory
scale bioreactor performance at the microscale.
It comprises single-use cell culture vessels,
automated workstation and powerful software,ambr® 15 cell culture is installed in a biologicalsafety cabinet for aseptic operation.
New flexible operation with flexible deck layout andexpanded tip bin capacity
Gas Supply Options

68

ambr® 15 Individual Gas Supply

38

The Generation 2 system offers improved
performance, increased flexibility and extended
capability to support more applications. It has
been developed to answer the challenges faced
as biotherapeutics become more complex,
and processes more intensified.
k Increases walk-away time to maximize operator productivity

New rapid vessel drain functionality and process steps k Enables clone stability studies, media exchanges andperfusion mimic processes to be performed
New liquid handler and culture station design

k Improves performance and allows lower stirrer speeds
for sensitive cell lines

New ambr® clone selection software, 1 year license

k Simplifies the clone selection data workflow helping
operators to select the best clones

Wide range of cell lines and processes

k Suitable for CHO, NS0, HEK293, T-cells, iPSCs, NK cells
and many more

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

2. Mini Bioreactors

ambr® 15 fermentation
Advanced Microbioreactor System
for Microbial Applications

Take a tour of the
Take
tour
of thefermentationambra® 15
ambr ® 15 fermentation
workstation
andworkstationand vessel
microbioreactor
microbioreactor
Overview Weblinks vessel
124

Applications• Strain selection• Vector screening• Media and feed development• Early process optimization• DOE studies

ambr® 15 fermentation is an automated, high throughput microbioreactor systemthat monitors and controls 24 cultures in parallel with working volumes from 8 – 12 mL.
ambr® 15 fermentation is dedicated tomicrobial applications. It provides a reliablemicroscale model for early stage microbial
screening and optimization experiments.
It comprises single-use microbial vessels,
automated workstation and powerfulsoftware, ambr® 15 fermentation is installed
in a biological safety cabinet for aseptic
operation.

Fed-batch operation supports highdensity fermentations, improving earlystage predictions of large scale bioreactor
performance compared to shake flask
or plate based cultures.
Now available with integrated online biomass
measurement for real-time continuous
growth measurement of microbial cultures.
Gas Supply Options

Pumped pH reagent and feed additionk Enables more predictive high cell density cultures

High kLa values

k Supports E.coli growth to over OD 200

Culture station stirrer control

k Representative conditions compared to lab scale bioreactors

Independent bioreactor control of pH, DO and tempk More reliable and scalable results than shake flasks

Automated sampling and addition of liquid feeds

k Reduces hands-on operator time and cost68

ambr® 15 Individual Gas Supply

39

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Mini Bioreactors

ambr® 15 Vessels
Single-Use Microbioreactor Vesselsfor High Throughput Screening

Applications
Clone or strain screening
Media development
Cell culture
Microbial fermentation

•
•
•
•

ambr® 15 automated bioreactor systems use irradiated single-use microbioreactor vessels
configured either for cell culture or microbial cultivations.
The ambr® 15 microbioreactor vessel design
incorporates single-use pH and pO2 sensor
spots, integrated impellers, vessel port withcap for sampling and liquid additions, andentry for gas supply. Microbial vessels haveadditional lines for base and feed.
The microbioreactors are easily loaded into
the culture stations prior to starting ambr® 15
cultivations.

40

Cell culture vessels for ambr® 15 cell culture
include a pitched blade impeller, they can besupplied with or without gas sparge line forheadspace gassing or gassing into the impeller
mixing zone.
Microbial vessels for ambr® 15 fermentation
include a Rushton impeller, gas sparge line,
supply plate and lines for base and feedpumped liquid additions.

Integrated pH and pO2 spots

k Provides highly predictive screening results undercontrolled bioreactor conditions

Integrated impeller and sparge tube

k Efficiently mixes liquid and gas, delivering scalable
results

10 –15 mL working volume (cell culture)
8 –12 mL working volume (fermentation)k Enables repeated culture sampling in a compact
and cost-effective format

Robotic compatible cap

k Improves productivity and reduces errors by automating
sampling, feeding and reagent addition

Irradiated single-use vesselk Enables same-day turnaround of the ambr® 15 system,
increasing throughput and reducing timelines

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix41

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Mini Bioreactors

ambr® 250 high throughput
Single-Use Multi-Parallel Bioreactor,
Fully Automated for Accelerated Process
Development

Find out about
®
Find
about
250
high
ambrout®
250 highambr
throughput
throughput
Overview Weblinks 124

Applications• Process development• Scale-down model

development• Process characterization

The ambr® 250 system is a high throughput, automated bioreactor system for processdevelopment with 12 or 24 fully featured single-use 100 – 250 mL mini bioreactors.
This is a completely integrated high throughput system with Easy Connect bioreactors andflexible software that enables scientists tomanage many experiments at the same time
while reducing the costs per experiment.

Gas Supply Options

68

ambr® 250 Individual Gas Supply

42

The ambr® 250 is ideal for scaling down
processes based on its fully featured
bioreactor design and provides a step change
improvement in lab productivity.

Fully automated 12- or 24-way bioreactor systemwith liquid handling capability and intuitive control
softwarek Manage more experiments in parallel and reducemanual handling cost per experiment

Fully disposable, single-use Easy Connect
mini bioreactors

k Fast turnaround of up to 24 bioreactors in lessthan one day

Classic stirred tank bioreactor design

k Provides excellent scalability to lab-scale bioreactors

Flexible software and individual control
of all process parameters

k Enables DOE optimization of all parameters,
ensuring implementation of QbD principles

Relatively small footprint and integrated biologicalsafety cabinet

k Flexible system – fit 12 or 24 bioreactors in
any laboratory

Positive displacement pumps and mass flow
controlled gassingk Highly accurate liquid and gas flow at low
flow rates

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

2. Mini Bioreactors

ambr® 250 Vessels
Fully Featured Single-Use
Mini Bioreactor Vessels

Applications• Process development• Scale-down model development• Process characterization

Each ambr® 250 automated bioreactor system uses 12 or 24 single-use mini bioreactors
with a working volume ranging from 100 – 250 mL.
The fully featured vessel design incorporates
an integrated single-use pH electrode andpO2 spot sensor. Each system is irradiated forsupply as presterilized units.

A simple three-step Easy Connect process
enables you to quickly hook up all the gas,­liquid and sensor lines to each vessel andthus significantly reduce the time needed to
set-up multiple bioreactor experiments.

You can choose between mammalian cell
culture vessels with pitch blade impellers or
microbial fermentation vessels with Rushton
impellers.
Fully featured, classic stirred tank vesselk Applicable as a scale-down model

Integrated Easy Connect gas and liquid in-line filters

k Simplifies the process of system set-up and results infast turnaround between experiments

100 – 250 mL working volume with baffles

k Reduces reagent costs and supports enhanced
off-line analysis

Polycarbonate vessel construction and integrated
pH electrode and pO2 spot

k Fully disposable with no need to clean between runs
or refurbish probes

Robotic compatible cap for samplingk Improves productivity and reduces errors by enabling
automated inoculation, feeding and sampling

43

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Mini Bioreactors

ambr® 250 high throughput
perfusion
The Fast Track to Intensified
Cell Culture Processes Development
Read about ambr ® 250
Read throughput
about ambr ® 250
high
high
throughput
perfusion
perfusion
Overview Weblinks 124

Applications
Perfusion cell culture
Process development
Intensified fed-batch
Continuous perfusion
Seed train optimisation

•
•
•
•
•

The ambr® 250 high throughput perfusion system is a high throughput, automatedbioreactor system for a range of applications in perfusion cell culture process development.
This next-generation perfusion bioreactor
system can enable and enhance yourperfusion process development in several
key areas, including seed train optimisation,
intensified fed-batch, and continuous
perfusion.

44

Different process types can be run in parallelor in series, including both perfusion andfed-batch process types.

Integrated single-use perfusion bioreactors

k Reduce complexity and setup time

Fully automated parallel systemk Increase experiment size and consistency

Industry standard bioreactor and perfusion filterk Results are predictive of larger scale performance

Lower media and labour costs

k Increased cost effectivenessEnables larger perfusion studies and DOE

k Improve development timelines and process
performance

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

2. Mini Bioreactors

ambr® 250 perfusion Vessels
Single Use Mini-Bioreactor Vessels
with Perfusion Capability

Applications• Perfusion cell culture• Process development• Intensified fed-batch• Continuous perfusion• Seed train optimisationambr® 250 high throughput single-use perfusion bioreactors include all key elements
required for perfusion culture, in a simplified and user-friendly format.
Single-use perfusion bioreactors significantly
reduce staff time needed for set-up andcleaning, and enable rapid system turnaround.
This increases system utilization efficiency
and helps to reduces development timelines.

High efficiency sparger

Integrated components further reduce set-up
time and minimize risk of lost experiments.
ambr® 250ht perfusion bioreactors areavailable in both alternating tangential flow(ATF) and tangential flow filtration (TFF)
variants.
k Supports very high cell densities

30 kDa or 0.2 µm filterk For product retention or flow throughSingle use pressure sensors

k Monitor transmembrane pressure

Perfusion pump systemk Performs crossflow and bleed functions

Integrated and irradiatedk Reduce complexity and setup time45

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Mini Bioreactors

ambr® 250 modular
Increased Productivity with
Simplified Operation

Find out more about
®
Find
more
about
250
modularambrout®
250
modularambr
Overview Weblinks 124

Applications• Process optimization• Process characterization• Process scale-down modelambr® 250 modular is an innovative easy-to-use benchtop bioreactor system that can be
expanded from a 2 to 8 bioreactor system, using fully integrated single-use 100 – 250 mL minibioreactors.
The system utilizes the same advanced stirredtank bioreactor technology pioneered in theoriginal ambr® 250 high throughput system.
The system comprises a series of elegantly
designed benchtop modules enabling

Gas Supply Options

68

ambr® 250 Individual Gas Supply

Classic stirred tank bioreactors

k Provide excellent scalability to lab-scale bioreactors

Benchtop bioreactor system that is modular andexpandable

k A flexible system that can be expanded to meetincreased demandSingle-use bioreactors are fully integrated to reagent k Increase productivity by enabling experimental set-up
reservoirs and syringe pumps
and turnaround to be carried out quickly and easily
Positive displacement pumps and mass flow
controlled gassing46

1– 8 bioreactors to be operated in parallel
and a control module with intuitive system
software accessed via a user-interface screen.

k Highly accurate liquid and gas flow at both high andlow flow rates

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

2. Mini Bioreactors

ambr® 250 modular Vessel
Fully Integrated Single-Use Mini Bioreactor
Vessels

Applications• Process optimization• Process characterization• Process scale-down model

The ambr® 250 modular bioreactor is a single-use bioreactor vessel that is fully integrated
to 5 reagent reservoirs and syringe pumps allowing for significant simplificationof experimental set-up.
Each bioreactor is fully integrated with
5 liquid reservoirs and proprietary single-use
syringe pumps.

Bioreactor fully integrated to reagent reservoir
and syringe pumps

The integration simplifies experimental set-up,
eliminates any need for sensor or pumpcalibration, and significantly reduces any error
due to manual handling.

k Allows for rapid experimental set-up and turnaroundSingle-use syringe pumps

k Enables highly consistent and accurate liquid delivery

Classical stirred tank vessel design

k Enabling accurate scale-down modelling

Single-use technology

k Eliminates need for sensor or pump calibaration
ensuring easy and rapid experimental set-up

47

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

3. Benchtop Bioreactors

BIOSTAT ® AYour Professional Start
to Controlled Cultivation

See how easy it can beSee
how easy
it can be
to control
a bioreactor
tocontrola bioreactor
Overview
Weblinks
124

Applications• Microbial fermentationand cell culture• Academic education andtechnical training• Early-stage research anddevelopment

BIOSTAT ® A is a minimum footprint and easy-to-use bioreactor | fermenter designed as anentry-level model for microbial fermentation and cell culture.
With its compact design, BIOSTAT ® A saves
valuable space in your laboratory. If you arelooking for a bioreactor for training purposesor for scale-up from shake flask to controlledcell growth, BIOSTAT ® A is the perfect fit.
BIOSTAT ® A is available in configurations for
microbial fermentation and for cell culture
applications.

It can be combined with the UniVessel® Glassin a range of 1 L, 2 L and 5 L, as well as withthe 2 L single-use UniVessel® SU. Using theadvanced package, you can operate it bya tablet or a smartphone and can perform
fed-batch processes.

BioPAT ® Sensor and Software Options:
Intuitive operation concept including operation
via tablet and smartphonek Speeds up training and reduces the riskof operating errors

Integrated, circulated cooling for microbial
fermentation

k Allows fermentation in any lab and minimizes
water usage

Simple and automatic aeration control

k No manual adjustment of flow meters andno pulsed aeration

Easy interchangeability between reusable andsingle-use culture vessels

k More flexibility every day

Fast Load pumps

k Easy, fast and safe handling of tubing• MFCS:
Supervisory Control andData Acquisition 84

Gas Supply Options

68

Additive Flow49

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Benchtop Bioreactors

BIOSTAT ® B
Check out the possibilitiesof BIOSTAT ® B

The Multi-Talent for Research andProcess Development

Check out the possibilitiesof BIOSTAT ® B
Watch Video on Sartorius
Benchtop
Bioreactor
WebsiteOverview
Weblinks
124

Applications• Microbial, insect and­mammalian cell culture• Suspension and microcarrier
cultivation• Process development• Process optimization• Process characterization

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement74• Trace:
Glucose | Lactate measurement 76• Fundalux:
Turbidity measurement• Xgas:Off-gas analysis

77

88• MFCS:
Supervisory Control andData Acquisition 84

With multiple thousand installations
worldwide, the BIOSTAT ® B is the market­leading benchtop system for various
R&D applications.

It is available with the UniVessel® Glass in arange of 1 L, 2 L, 5 L and 10 L, as well as withthe 2 L single-use UniVessel® SU and with the
RM Rocker in a choice of 20 L and 50 L.

One BIOSTAT ® B control tower controls up to
two culture vessels completely independently,
saving valuable bench space.
Stirred and rocking motion, reusable and single-use
culture vessels – all controlled with one DCU towerk Flexibility of bioreactor system – suitable forvarious demands

Single or twin set-up for control of one or two
culture vessels

k Saves valuable bench space

Configurable design thanks to variety of flexible
and scalable options

k Fully configurable BIOSTAT ® B meets customer
specific needs

Additive Flow

12” touch screen and stainless steel housing

k Simple to operate and easy to clean

Advanced Additive Flow

Gassing system comparable to our BIOSTAT STR®
with up to four mass flow controllers

k Straightforward process transfer to production-scale,single-use bioreactors

Gas Supply Options

50

The BIOSTAT ® B is our universal benchtop controller for stirred and rocking motion systems.

68

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

3. Benchtop Bioreactors

BIOSTAT ® B-DCU
The Ultimate Tool for the Developmentof Intensified Bioprocesses

Learn more about the
®
Learn
more
about theB-DCU
BIOSTAT®
B-DCU
BIOSTATas Perfusion
BioreactorasPerfusion
Bioreactor
Overview
Weblinks
124

Applications• Perfusion & concentrated
fed-batch processes• Mammalian, microbial
and insect cell cultures• Process optimization• Process characterization• Process development

The BIOSTAT ® B-DCU is designed to meet demanding requirements in process optimizationand characterization – especially for intensified bioprocesses.
®

®

The BIOSTAT B-DCU provides enhanced
functionality and an unrivalled level of options
to flexibly design process control strategies.
It is the ideal scale-down bioreactor model forcell culture and microbial processes as it canemulate process strategies used at production
scale. The unique system design enables theindependent operation of up to six culture
vessels and makes it an ideal tool for MSAT
as well as process optimization andcharacterization teams.

The BIOSTAT B-DCU can be combinedwith glass culture vessels, ranging from
1 L, 2 L and 5 L to 10 L, and with the 2 L
single-use UniVessel® SU.

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement• Trace:
Glucose | Lactate measurement 76• Fundalux:
Turbidity measurement

Advanced and precise control of multiple
liquid lines for feed, bleed and permeate flowplus fully flexible aeration options makeour BIOSTAT ® B-DCU the ultimate tool forthe development of intensified bioprocesses
with ultra high cell densities.

• Xgas:Off-gas analysis

Integration of advanced BioPAT ® sensor andprocess control options

k Better process control and optimization options leadto improved titer and quality

Gas Supply Options

Connectivity to third party supervisory software
including DeltaV™ 1

k Integration into existing supervisory control infrastructure
reduces human error and improves data consistency

O2 Enrichment

Large number of configuration options, based on
decades of experiencek Reliability and flexibility for seamless scale-up andscale-down allows hassle-free process optimizationand characterization

Superior gas mixing with up to six smart mass flow
controllers with a 1:200 flow rangek Accurate oxygen control across large cell density range
and precise down scalling of large scale bioreactors

1DeltaV™ is a trademark of Emerson Process Management

74

77

88

• MFCS:
Supervisory Control andData Acquisition 84

68

Additive Flow
Advanced Additive Flow51

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Benchtop Bioreactors

UniVessel® Glass
Multi-Purpose Glass Culture Vessel
Get more information
Get
more
about
the information
features ofaboutthe® features
Glass ofUniVessel®
Glass 124
UniVessel
Overview Weblinks

Applications• Perfusion and concentrated

fed-batch processes• Microbial fermentation(bacteria, yeast, fungi)• Animal cell culture(mammalian, insect)• Adherent cell cultures

on microcarriers• Process development andoptimization• Scale-up and scale-downstudies

UniVessel® Glass culture vessels are specifically tailored to the needs of biopharmaceuticalprocess development e.g. for such as monoclonal antibodies, recombinant proteins and vaccines.
The autoclavable UniVessel® Glass can be
configured according to individual needs.
Over 50 years of experience in designing­scalable bioreactors have gone into the­making of UniVessel® Glass. Numerous
scientific articles on its scalability and reproducibility have meanwhile been published.
Bottom drain option

Our recently launched new design is lighter,easier to handle and dishwasher proof. The
special bottom drain version makes it ideal for
ATF and TFF based intensifed processes.

Configuration Examples
For microbial culture, with double-wall­vessel, Rushton impellers, baffles, inoculation
port and ring sparger
For cell culture, with single-walled vessel,
3-blade segment and Rushton impellers,
micro-sparger and dip tube for gentle
inoculation.

Lighter design, easier to handle and dishwasher proof k Quick turnaround, easy to use

52

Classic stirred-tank design, characterization
data available

k Straightforward scale-up

Fits into small autoclaves

k Saves investing in new autoclave

Choice of 1 L, 2 L, 5 L, 10 L working volumes

k Flexible interchangeability between vessel sizes
without extra investments into a new controller

Fits to all BIOSTAT ® benchtop systems

k Lowers the investment budget for new controllers as
the available UniVessel® Glass can be used

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

3. Benchtop Bioreactors

UniVessel® SU
Single-Use Bioreactor, Proven Design,
Ready for the Future

Turn the production
Turnthetoproduction
process
single-use
processtosingle-use
Overview Weblinks
124

Applications• Mammalian and insect

cell culture• Suspension and microcarrier

cultures• Process development andoptimization• Seed expansion

The UniVessel® SU is a stirred-tank single-use bioreactor with a working volume rangeof 0.6 – 2 L. It is entirely single use from vessel to sensors and can easily be connected toexisting bioreactor controllers.
It combines the proven, scalable designof glass bioreactors and the fast turnaroundof single-use systems. UniVessel® SU can beeasily integrated into both new and existingbioreactor controllers in customer's lab. The
optical holder guarantees secure vessel standand its built-in single-use measurements for
pH and DO minimize vessel preparation time.
All single-use from vessel to sensors

It can be used interchangeably with glass
vessels to help efficiently manage peak workloads despite challenging timelines. Since
discarding the complete vessel after one use,
the user hasn't to bother with the hassle ofcleaning, autoclaving and reinstallation.

k Achieves turnaround in less than an hour

Compatible with your available bioreactor controllers k Enables you to utilize your existing controllers
with cutting-edge, single-use vessels and sensors;no additional investment in new controller neededInterchangeable with glass vessels

k No more bottlenecks during peak workloads

Proven and scalable designk Same design principles as glass bioreactors and
BIOSTAT STR®, to reduce time and effort for processdevelopment, optimization and validation

53

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

4. Single-Use Bioreactors

BIOSTAT® RM TX
with Flexsafe® RM TX Bags
Culturing Consistent Quality Products
for Cell Therapy Applications
Learn more about the
®
Learn
more
about
thecellRM
TX for
BIOSTAT®
RM TX for cell
BIOSTAT
therapy applications
therapy
applications
Overview Weblinks
124

Applications• Process Development• Immunotherapy• Ex vivo expansion ofpatient-specific T-cells
and | or T-cell subsets

The BIOSTAT ® RM TX and Flexsafe® RM TX bag combination provides an automated,wave-mixed and closed environment suitable for optimal growth of cell products in working
volumes up to 5 L.
The system supports the culturing of
consistent quality cells and is perfect for small
volume autologous processes with multiparallel scale out needs. Using this system,
one Flexsafe® RM TX bag can be controlled
and monitored via the BIOSTAT ® B
control unit.

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement• MFCS:
Supervisory Control andData Acquisition 84

Gas Supply Options

68

Advanced Additive Flow

54

74

For scale-out, two Flexsafe® RM TX bags
and two separate rocking platforms can be
attached to a twin BIOSTAT ® B control unit.
Fed-batch, perfusion processes or a combination of culture modes are possible with
the BIOSTAT ® RM TX.

Fixed perfusion membrane at the bottom of the bag, k Minimal loss or damage of the cells
for removal of cell free media during perfusion process
Single-Use sensors for pH, DO and viable biomass

k To enable sophisticated process control with reduced
sampling need

100% integrity tested, gamma-irradiatable and fully
validated Sartopore® Air sterile filters

k Continuous protection of the culture fromcontamination

Unique gravity harvesting concept (see picture)k To maximize cell recovery

Walk-away automated analysis and control

k For robust & consistent manufacturing

Complete qualification of the systemk For GMP use to support regulatory compliance

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

4. Single-Use Bioreactors

BIOSTAT ® RM 20 | 50
Easy-to-Use Rocker

Learn more about the
®
Learn
more
about
RM
as a thefully
BIOSTAT®
RM aswavea fully
BIOSTAT
GMP
compliantGMP
mixedcompliant
bioreactorwavemixed
Overviewbioreactor
Weblinks 124

Applications• Mammalian, insect andplant cell cultures• Suspension cells andadherent cells on­microcarriers• Low to medium density
microbial cultures• Expansion and differentiation of stem cells• Rapid material supply for
preclinical trials• Production of recombinant
proteins, mAbs and vaccines

The BIOSTAT ® RM is a fully GMP compliant single-use, wave-mixed benchtop bioreactor.
It is perfectly sized and suitable for stand alone use or in combination with a control tower(BIOSTAT ® B).
It features an exchangeable bag holder tofit bags with a total volume of 1– 50 L.
The BIOSTAT ® RM basic rocking platform
with an integrated local controller, optional
Air | CO2 mixing module and load cells is
the optimal choice for straight-forward
applications, such as seed generation.

For more sophisticated process control the
BIOSTAT ® RM basic can be combined with
the BIOSTAT ® B tower to run fully automatedand controlled batch, fed-batch or high celldensity perfusion cultures.

Individual control of two bags on one platformk Space-saving

BioPAT® Sensor and Software Options:

Advanced alarming and safety features

k Safe cultivation

Automated sampling function

k Reduced manual handling• ViaMass:
Viable biomass measurement

Basic configuration in combination with BIOSTAT ® B
controller

k Maximum process flexibility

Advanced process analytical sensor options
in combination with BIOSTAT ® B controller

k For increased process safety and reduced
sampling need74

• MFCS:
Supervisory Control andData Acquisition 84

Gas Supply Options

68

Advanced Additive Flow55

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

4. Single-Use Bioreactors

BIOSTAT ® B with
RM 200 Rocker
Learn more about the
®
Learn
more
about
RM
200 the
BIOSTAT®
200
BIOSTAT
rockeras aRMlarge-scalerockeras a large-scalebioreactor
bioreactor
Overview Weblinks 124

Large-Scale, Rocking-Motion,
Single-Use Bioreactor

Applications• Mammalian, insect andplant cell cultures• Suspension and adherent
cell cultures on microcarriers• Low to medium density
microbial cultures• Shear-sensitive cells, such asstem cells• Large-scale seed expansion• Small-scale productionof recombinant proteins,
vaccines and mAbs

The BIOSTAT ® B with RM 200 rocker is a single-use, rocking motion bioreactor forlarge-scale. Flexsafe® RM 100 L and 200 L bags are also available with a bag integrated
perfusion filter. This solution is ideal for intensified seed supply without the need foran external cell retention device, e.g. ATF.
BIOSTAT ® B with RM 200 rocker is the ideal
choice for production-scale seed expansion
and rapid material supply for preclinical andclinical studies using proven rocking motion
technology.
The bag holder fits Flexsafe® RM bags
providing working volumes up to 100 L.

Flexsafe® RM bags can be used in your seed train
processes and scaled up to the BIOSTAT STR®
single-use, stirred tank bioreactors equippedwith Flexsafe STR® bags. Thereby the samepolyethylene film material can be used acrossall cell culture steps.

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement• MFCS:
Supervisory Control andData Acquisition 84

Gas Supply Options

68

Advanced Additive Flow56

74

Low consumable costs

k Economical alternative to stirred single-use
bioreactors

Well-proven technology with intuitive design

k Easy to operate

Precise gravimetric harvest and feed controllers

k Reliable and efficient cultivation

Independent controller and rocking platform unitk Flexible space-saving component arrangement

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

4. Single-Use Bioreactors

Flexsafe® RM
Excellent Growth in Flexsafe®
Bioprocessing Bags

Applications
Mammalian cells
T-cells
Insect cells
Plant cells
Stem cells
Microbial cells

•
•
•
•
•
•

The Flexsafe® RM is a single-use bioreactor bag available in multiple
sizes and configurations. The control of the complete manufacturing process, from resin to
the final bag, ensures consistent and reproducible quality of the Flexsafe® bioprocessing bags.
This has been proven by excellent and lot-tolot consistent cell growth performance of thismultilayer polyethylene film. Our BIOSTAT ® RM
bioreactors use rocking motion mixing technology which is ideal for cell cultivation withlow shear stress. Flexsafe® bags are available in
1 L, 2 L, 10 L, 20 L, 50 L, 100 L and 200 L size
as basic, optical and perfusion configurations,with or without BioPAT ® ViaMass. Basic bags
are designed for use in seed train and production applications without pH and DO control.

Optical bags feature integrated single-use
opto-chemical pH and DO sensors, which are
already pre-calibrated. Perfusion bags areavailable in two versions:•	with integrated 1.2 µm perfusion
membrane (PES)•	ATF perfusion bags are designed for theconvenient connection to an external cellretention device via OPTA connector.

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement

Strong and flexible filmk Ultimate process safety | fast & easy handling

Optimized and fully controlled film formulation

k Consistent cell growth, security of supply

Basic, optical or perfusion bag designs

k Wide range of standard bags is suitable formany different needs and applications

Integrated single-use sensors for measurementof viable biomass, pH and pO2

k Reduced operator interaction enables higher
automation level and thereby decreases
contamination risk

74

57

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

4. Single-Use Bioreactors

BIOSTAT STR®
Learn more about the
®
Learn
more
the
bioreactor
BIOSTATSTRabout®
bioreactor
BIOSTAT
STR
familyfamily Weblinks 124
Overview

Perfect Match for True Scalability
in Single-Use

Applications• Antibodies, recombinant
proteins, vaccines, cell &gene therapy• High cell density exceeding
150 million cells /mL• Adherent cell culture
on microcarriers• Process development andscale-up• Seed expansion

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement

74

The BIOSTAT STR® single-use bioreactor design is based on the gold standard of conventionalstirred-tank bioreactors.
Simplify the scale-up and scale-down,minimize the risk of your process transfersand easily switch between stainless steel
and single-use bioreactors.

Get the best solution for high cell density­continuous cultures and microcarrier cultures.
BIOSTAT STR® is available with working volumesof 50 L, 200 L, 500 L, 1,000 L and 2,000 L.

• MFCS:
Supervisory Control andData Acquisition 84

BIOSTAT STR® makes all this possible thanks
to its classic stirred-tank design, comparable
mixing and gassing strategies and reliable
single-use sensor platform.

The latest generation design offers a numberof features such as connectivity to our
BioPAT ® MFCS or 3rd party supervisory software
like DeltaV™ 1.

Gas Supply Options

Geometrical similarity of vessel designk Straighforward scalability between scales andfrom multi-use systems

Proven stirrer design with two impellers
on central shaft

k Excellent fluid flow dynamic – minimized mixing time

Advanced aeration concept

k Excellent oxygen transfer and CO2 removal atminimized foaming

Advanced single-use pH and pO2 sensors

k Low contamination risk; easy and quick handling

Easy integration into 3rd party distributed
control system (e.g. Delta V™ 1 )k Reduce operator training and mitigate human error• Trace:
Glucose | Lactate measurement 76• Xgas:Off-gas analysis

88

68

Additive Flow
Advanced Additive Flow

158

DeltaV™ is a trademark of Emerson Process Management

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

4. Single-Use Bioreactors

Flexsafe STR®
Single-Use Bags for BIOSTAT STR®

Learn more about
Learn
more about
the Flexsafe
STR®
the
Flexsafe
STR®
single-use
bags
single-use
bags
Overview Weblinks 124

Applications• Suspension or adherent cell
culture on microcarriers• Mammalian, insect andstem cell culture• Low to medium cell density
microbial culture

Flexsafe STR® single-use bags for our BIOSTAT STR® bioreactor are a member of ourbioprocessing bag family, combining outstanding cell growth, robustness and assuranceof supply.
Flexsafe STR® facilitates single-use manufacturing there by meeting the most stringent
customer needs for safe bioprocessing.
Flexsafe STR® bags are configurable, offering
multiple options for tubing, connectivity tocell retention devices (ATF type), spargers andimpeller combinations. The preferred singleuse pH sensor can be choosen between theproven optical technology and the new drystorage electrochemical solution.

Pre-configured standard bags are available
from stock.
The same polyethylene film material canbe used across all cell culture steps.
Flexsafe® RM bags can be used in a seed train
process, e.g. together with our BIOSTAT ® RM
bioreactors. For media storage, shipping andbulk harvest hold. Flexsafe® 3D bags canbe used.

* Available bag working volumes:
50 L, 200 L, 500 L, 1,000 L, 2,000 L

BioPAT® Sensor and Software Options:• ViaMass:
Viable biomass measurement

Robust bag with telescopic shaft

74

k Easy installation and reliable operation

Complete control of film raw materials

k Consistent lot to lot cell growth performance

Sterile connection and disconnection devices

k Safe liquid transfer

Needle-free sampling port

k Easy and convenient sampling

59

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

4. Single-Use Bioreactors

Flexsafe STR® Point-of-Use
Leak Test
Process Safety with Bag Post-Installation,
Pre-Use Testing

Learn more about
Learn
more about
the Integrity
Testingtheincl.Integrity
bag test Testingincl. bagWeblinks
test
Overview
124

The innovative Sartocheck® 4 plus bag tester technology applied to Flexsafe STR® single-use
bioreactors will secure processes in case the bag got damaged during transportation etc.
Intactness of Flexsafe STR® single-use
bioeractors can be easily checked at point of
use to ensure an optimal process and operator
safety thanks to fully validated and qualified
technology.

60This non destructive method will prevent
batch losses, time and money waste due
to potential bag mishandling.

Post-installation, pre-use pressure decay testingk Mitigate risk of batch losses
k Keep projects timelines on track

Test bag and connections until the first clamp

k Check bag intactness just before use

Patented, qualified non destructive technology

k Reliably and reproducibly detects leaks

Single-use and easy to use fleeces

k Low impact on process timeline

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

4. Single-Use Bioreactors

Holistic Safety Conceptof BIOSTAT STR®
Biosafety
Production

Transportation

Installation

Operation

Deinstallation

Sartorius has developed a holistic safety concept, from production site
to post-use disposal, which brings ultimate safety to single-use bioprocessing.
Production• Incoming goods inspection• ISO7 cleanroom bag assembly• Qualified staff and manufacturing SOPs
• Stringent quality control
Transportation•	Innovative packaging concept protects bag
until final installation
Installation•	System designed for convenient installation
to reduce operator manipulation•	Detailed instructions in operating manual
available•	Video installation guide available•	Aseptic connector technology•	Bag tester for point-of-use leak test

Operation• Proven cell culture performance•	Extensive application-based robustness
qualification•	Pressure measurement and control keeps
bag pressure within permissible range•	Single-use exhaust cooler eliminates
blockage of exhaust filter•	Overheating protection to maintainmaterial properties•	Completely closed bag with non-invasive
magnetic coupling and single-use sensors•	Spill tray with direct connection to kill tank
Deinstallation•	Aseptic disconnection•	Convenient disassembly61Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

4. Single-Use Bioreactors

Flexsafe® Bag Family
Safe and Convenient Single-Use Processing

Flexsafe® – One Film Across All Single-Use Applications
Flexsafe® meets the requirements for outstanding robustness and ease of use throughout
all steps of single-use processing – from rocking motion or stirred tank bioreactor cell
culture, through to large-scale mixing to shipping of drug products. In addition, Flexsafe®
reduces time and expense for process validation, extractable and leachable studies,toxicology assessment and stability studies.

One for All
Learnmoremoreabout
aboutthetheLearn®® bag family
Flexsafe
Flexsafe bag family
Overview Weblinks

124

Watch Video: New Bag Family

62

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Cell Density

Cell Growth

Reference: Borosilicate Glass
Flexsafe® Bags
Standard Bags

Time

Flexsafe® ensures excellent and reproducible growth
behavior of the most sensitive production cell lines.
The complete control of our raw materials, the extrusion
process and the bag assembly guarantees consistent
lot-to-lot cell growth performance.
We optimized the resin and minimized the additive
package, in collaboration with our resin and film
suppliers.
Independent labs have confirmed that Flexsafe® bags
are free of cytotoxic leachables. No bDtBPP is identified
in WFI extracts of Flexsafe® bags.

Robustness

Bag A
Bag B
Bag C
Flexsafe®
Energy at BreakThe thickness, strength and flexibility of the newpolyethylene film enhances the mechanical robustness
of Flexsafe® – making it ideal for all bioprocessing
applications. The strength of Flexsafe® significantly
reduces the risk of accidental damage to the bag
due to inappropriate handling. Its flexibility enables
convenient installation and self-deployment of
the bag in its container.

Assurance of Supply

Complete control of ourmanufacturing processfrom resin and film extrusion
to final bag assembly

Flexsafe® provides you with an unprecedented
assurance of supply and enables robust business
continuity plans. Our strategic partnership with resinand film suppliers ensures full traceability of raw
materials and control over the entire manufacturing
process from the resins to the final assembled bags.

63

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

4. Single-Use Bioreactors

Rely on Proven Scalability –Accelerate The Development
Sartorius Stedim Biotech offers classic stirred-tank design in single-use bioreactors,
from ambr® 250 to BIOSTAT STR® 2000.

– Geometrical similarity of vessel design

Simplify your scale-up and scale-down studies– Consistent mixing and gassing strategies

Easily switch between reusable and single-use bioreactors– Reliable single-use sensor platform

Mitigate risks during process transfersambr® 250
100 – 250 mL
working volume

UniVessel® SU 2 L
0.6 – 2 L
working volume

Cell line Development

BIOSTAT STR® 50
12.5 – 50 L
working volume

Process Development

BIOSTAT STR® 200
50 – 200 L
working volume

BIOSTAT STR® 500
125 – 500 L
working volume

Production– Mammalian, insect and stem cell culture– High cell density cultures exceeding 150 million cells /mL– Adherent cell culture on microcarriers– Low to medium cell density microbial culture64III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Seamless scalability in single usefrom early process development
to commercial production

250 mL

2L

BIOSTAT STR® 1000
250 – 1,000 L
working volume

50 L

2000 L

BIOSTAT STR® 2000
500 – 2,000 L
working volume– Antibodies and recombinant proteins– Vaccines– Cell and gene therapy

For further details please have a look at:www.sartorius.com/biostat-str
atour website.

65Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

5. Stainless Steel Bioreactors

BIOSTAT ® Cplus
The Stainless Steel Fermenter | Bioreactor
for Your Laboratory
Learn more about the
®
Learn
more
about
Cplus
as thea
BIOSTAT
as a
BIOSTAT ® Cplus
laboratory
stainlesslaboratory
stainlesssteel fermentersteelfermenter
Overview Weblinks 124

Applications• Microbial and cell culture• Suspension and microcarrier

cultures• Process development andscale-up• Seed production• Protein supply for researchand development

BioPAT® Sensor and Software Options:• Trace:
Glucose | Lactate measurement 76• Fundalux:
Turbidity measurement• Xgas:Off-gas analysis

77

88• MFCS:
Supervisory Control andData Acquisition 84

Gas Supply Options

68

The BIOSTAT ® Cplus is available with a selection of culture vessels with working volumesof 10 L, 15 L, 20 L and 30 L. A benchtop
version is available with a 5 L working volume
culture vessel. The system can be flexibly
integrated into an existing laboratory infrastructure. The culture vessel can be sterilized
by electro or steam heating. The casters under
the supply unit of the bioreactor enable it

to be easily moved to another location.
Extended functionality and ease of use isprovided by a wide choice of in-line sensors
and anaylzers with an integrated displayof process values on the DCU screen. For
enhanced system performance, the powerful
SCADA software BioPAT ® MFCS is available
with an optional S88 recipe control module.

Compact and mobile design

k Saves valuable laboratory space and easy to relocate

O2 Enrichment

Closed loop temperature control systemwith a choice of steam or electrical heatingk Highly precise temperature control that matches yourlaboratory infrastructure

Additive Flow

Automatic Sterilization In Place (SIP)k Minimizes manual operation

Open frame piping skid

k Easy to access during operation and maintenance

Advanced Additive Flow

66

BIOSTAT ® Cplus is a fermenter | bioreactor developed for the fermentation of microorganisms
and cultivation of animal cells.

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

5. Stainless Steel Bioreactors

BIOSTAT ® D-DCU“Fast Lane” to Production

Learn more about the
®
Learn
more
aboutasthe
D-DCU
the
BIOSTAT®
D-DCU
as theBIOSTAT
fastlane toproduction
fastlaneWeblinks
to production
Overview
124

Applications• Microbial and cell culture• Suspension and microcarrier

cultures• Process development andscale-up• Seed production• GMP Production

The BIOSTAT ® D-DCU is designed for demanding requirements in process development
and small scale production.
The system offers an excellent solution for any
budget and every need. Working volumes areavailable in a choice of 10 L, 20 L, 30 L, 50 L,
100 L and 200 L. Scalable BioPAT ® MFCS S88
recipes provide a significant increase inprocess safety and reliability and result in
improved batch-to-batch consistency.
Due to the bioreactor’s modular design,
various configurations are available – frombasic to fully featured. The BIOSTAT ® D-DCU
can be equipped with an automated CIP
system. It can be connected to a mobile unit

for easy and convenient cleaning of the vessel
and transfer lines. Alternatively, it can be
powered and integrated into a hard pipedsystem in your facility.
It is designed to interface single-use storage
bags for media addition and harvesting,as well as the TAKEONE® single-use aseptic
sampling systems. Further enhanced
functionality and ease of use are provided
by a wide selection of in-line sensors andanalyzers and by integrated display of process
values on the DCU screen.

Single or twin configuration

k Saves valuable space

Automatic Sterilization In Place (SIP) and
Cleaning In Place (CIP) sequencesk Minimizes manual operation

Powerful industrial DCU control system

k Reliable and flexible to grow with your needs

Gear-free, low-noise agitation systemk For silent operation even at a high agitation speed

Fully configurable from basic batch set-up
to sophisticated configurations supporting advanced
gassing and feeding strategies

k Meets virtually all process requirements

BioPAT® Sensor and Software Options:• Trace:
Glucose | Lactate measurement 76• Fundalux:
Turbidity measurement• Xgas:Off-gas analysis

77

88• MFCS:
Supervisory Control andData Acquisition 84

Gas Supply Options

68

O2 Enrichment
Additive Flow
Advanced Additive Flow67

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

6. Bioreactor Control

Gas Supply Options
ambr® 15
Individual Gas Supply

CO2 | N2

Sparger* or

O2 | Air

Overlay*

Air | Air
O2 | O2cell culture | microbial

Typical gases used are Air | O2 | CO2 for ambr®
15 cell culture and N2 | Air | O2 for ambr® 15
fermentation. Each gas is added individually
into the supply line for each bioreactor vessel.
The mixed gas is delivered to the culture via
sparger or overlay according to the type ofambr® 15 vessel being used.

* Depending on vessel type.

ambr® 250
Individual Gas Supply
N2 | CO2

Air | Air or N2

Sparger andSparger

Overlay

O2 | O2cell culture | microbial

Switch valve
Dosing shutoff valve
Mass flow sensor

68* The diagrams shown are examples.
The detailed design depends on the specific­configuration of the ambr ® gassing strategy.

This advanced gassing strategy utilizes both
mass flow controllers and valves to accurately
control flow rates. The strategy directs any or
all of the 3 gases (Air, O2, N2 | CO2) to the
sparger or overlay independently. Any twogases can be accurately mixed, for example
when enriching gas with oxygen, either as apercentage of the total flow or as an addition
to the current gas flow. Gas actual flow rates
are monitored and controlled digitally via
the user interface.

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

O2 Enrichment
This gassing strategy uses a 3 | 2-way solenoid
valve to direct either an air or O2 flow to the
sparger. A manual flow meter visuallyindicates and controls the flow rate. O2 ispulsed via a solenoid valve, when required
to maintain the dissolved oxygen setpoint.
Air is not provided at this time. Optionallymass flow controllers can be integrated tomeasure and control the total gas flow rate
via manual adjustment or automatically in
conjunction with the controller, based on
the signal of the pO2 probe and the selected
setpoint.

Air

SpargerO2

Additive Flow
Controls the flow rate of air and O2
individually, (N2 and CO2 also possible but
not shown) to a single output, either asparger or overlay.

Sparger

Air

O2Advanced Additive Flow
Direct air, O2, N2 and CO2 can be directed tothe sparger and to the overlay. Flow meters
visually indicate the flow rate for each gas.
Add an additional gas flow path to the sparger
or overlay outlet. Select optional mass flow
controllers for each flow path, and switch
gases between overlay and sparger.
The detailed design of the Advanced Additive
Flow gassing approach depends on particular
BIOSTAT ® bioreactor system and configuration.
Please contact your the Sartorius representativefor further details.

OverlayAir

Sparger

O2

N2

CO2

Flow controller
Optional gas switch
Dosing shutoff valve
Optional dosing shutoff valve* The diagrams shown are examples.
The detailed design depends on the specific­configuration of the BIOSTAT ® gassing strategy.

Flow controller

3|2-way solenoid valve

Optional gas switch

Mass flow controller

Dosing shutoff valve

Optional mass flow controller

Optional dosing shutoff valve

Optional gas flow path3|2-way solenoid valve

69

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

6. Bioreactor Control

Oxygen Control Strategies
Solenoid Valves and Mass Flow Controllers
Choose between two options for controlling the gas flow into a B­ IOSTAT ®: solenoid valves (SVs)and mass flow controllers (MFCs). SVs operate electromechanically, switching on or off anddiscontinuously dosing a fixed flow rate of gas when a specific electric c­ urrent is applied. MFCs
are designed and calibrated to a ­specific type of gas in a particular range, and use a proportional
control valve to realize a continuous gas flow. The accuracy of a MFC is typically 10-fold betterand offers increased flexibility for an oxygen control strategy.

Cascade Gassing Control

Cascade Gassing Control

Automatic pO2 control is one of the mostimportant functionalities of a bioreactor.
It is designed to alter the volumetric oxygen
transfer rate in order to meet process oxygen
demands. As the measured pO2 moves off theset point, the system will automaticallychange a parameter (over a defined range)in order to re-establish the pO2 set point.
Freely select between different control
parameters such as stirrer speed, air flow or
oxygen percentage. Each parameter is placedin a cascade order. Once the parameter’s limit
has been reached the BIOSTAT ® controller will
shift to the next cascade until reaching theset point.

Cascade 1
Air

Cascade 2
O2

Cascade 3
Stirrer

Max
60.0%

Max
30.0%

Max
7.5%

Min

Min

Min

5.0%

0.0%

0.5%

Oxygen Demand

Advanced pO2 Control
Enable parallel modification of all physical parameters with the advanced pO2 controller.
Activate or change multiple parameters simultaneously such as stirrer speed, aeration rate
for air | oxygen or other parameters. All oxygen control strategies can be realized and beresource efficient. For examples see below visuals:
Constant Gas Ratio Constant Gas Ratio

Constant Gas Flow Constant Gas Flow

Air
lpm
O2
lpm
Stirrer
rpm

20

20

20

10

10
0

0

0

40

40

40

40

2

18 18

40 40

Oxygen Demand

Constant gas flow decreases the flow of airand simultaneously increases oxygen gas

70

2

Air
lpm

5

5

5

O2
lpm

5

5

5

40

40

40

Stirrer
rpm

10

10

40

Bubble Size Optimization
Bubble Size Optimization
20 20

20 20

40 40

Oxygen Demand

Constant gas ratio, where both air andoxygen % are increased at the same rate

Air
lpm

5

5

5

O2
lpm

5

5

5

40

40

40

Stirrer
rpm

10

20 20

10

20 20

80

80

Oxygen Demand

Bubble size optimization enables finetuning of the oxygen % and gas-liquidinterface area
lpm: litre per minuterpm: revolutions per minute95III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Advanced Measurement
and Control Loops
Glucose Feed Control
The BioPAT ® Trace monitors glucose andlactate online in both microbial and mammalian cultivations. This analyzer combines
single-use bio sensors and fluidic elements
to provide real-time glucose concentration
data which can be fed into the BioPAT ® DCU
or MFCS. From there the software enables
control loops for automated glucose feeding
to ensure virtually constant in-process
glucose concentrations.

Integrated Fast
Load pumps®

UniVessel® SU

BioPAT ® Trace

BioPAT DCU or MFCS

Metabolic Respiration Control
The BioPAT ® Xgas off-gas sensor and MFCS
software with the S88 recipe module can
automatically adjust the aeration, agitationand oxygen percentage to the respiration
requirements of individual cells. As a result,
this upstream control loop enables optimal
growth conditions, ultimately increasing
the productivity of customer process.

Mass flow
controllers andimpeller speed

UniVessel® Glass

BioPAT ® Xgas®

BioPAT DCU or MFCS

Viable Biomass Feed Control
Collecting real-time data about viable cellvolume enhances process understanding
and control capabilites. It allows continuous
adjustment of feed pumps and perfusion
rates as the biomass changes. As the BioPAT ®
ViaMass is fully integrated, the BIOSTAT ® canbe configured to indicate trigger points atdesired viable cell volumes rather than using
a set cultivation time. This considerably
improves the consistency and reproducibilityof batches.

Integrated Fast
Load pumps

BIOSTAT ® RM

BioPAT ® ViaMass
BioPAT ® DCU or MFCS

71

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

7. Process Analytical Technologies

Sartorius Process Analytical
Technologies
Biopharmaceutical production processes have changed significantly due to overall titerimprovements and the increasing deployment of single-use technologies. The introductionof robust and reliable single-use sensors further enhances the benefits of single-use processing
concepts. They enable you to use Process Analytical Technology (PAT) approaches for effective
automation and optimization.

Implementation of process analytical technologies results in risk mitigation, simplified
process changes and cost savings.

Process Economics

Yields & Titers• CoGs | R&D costs• Tech Transfer• Time to Market

Process Optimization &Process Understanding
Process Analytics | SCADAMVDA | Sensors | DOE

Product Safety

Critical Process Parameters
Design Space• Ease of process changes• Robust Manufacturing

Process Analyzers and Sensors
Collect real-time data for advanced process control strategies, which will ultimately improvethe economy and safety of your processes. Sartorius provides a comprehensive range of process
analyzers and sensors for your process needs.
Single-use sensors for pH and pO2;
fully integrated into our BIOSTAT ® bioreactors

k Enable real-time monitoring and control

Process analyzers for online measurement of glucose, k Ensure consistent process and product quality
lactate and other metabolites
Automated biomass measurement for single-use,glass and stainless steel bioreactors

k Ensures batch-to batch consistency

Process Control and Software Tools
Stable and robust processes require automated control of critical process parameters basedon reliable data acquisition, storage and evaluation capabilities. Process control and softwaretools further pave the way towards a knowledge-based approach to biopharmaceuticalproduction to mitigate risk.

72

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

SYNCHRONIZEDPATSOLUTIONS

73

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

8. Process Analyzers and Sensors

BioPAT ® ViaMass
Learn more about
Learnmore® about
ViaMass as
the BioPAT®
ViaMass as
theBioPATbiomass
measurement
biomass
sensor measurement
sensor Weblinks 124
Overview

Inline Biomass Measurement
for Process Control

Applications• 24|7 monitoring of viable

cell volume• Automated feeding based on

biocapacitance• Viral processes: Determinationof infection and harvest timepoint
• Cell therapy: Process monitoring without contamination
risk and volume reduction• Intensified processing:Automated cell bleed control
based on biocapacitance

BioPAT ® ViaMass measures the viable cell volume using the principle of biocapacitance, which is
selective to viable cells only. The SU sensor is fully integrated in Flexsafe STR® and Flexsafe® RMbags and comes presterilized with a plug-and-play integration. For easy process development,
the sensor is also available as a multi-use stainless steel probe for all our UniVessel® benchtop
reactors. BioPAT® ViaMass is fully integrated in the Sartorius control unit and feedback loops
can easily be implemented.

8Capacitance (pF.cm-1)

7

R2 = 0.9539

6
5
4
3
2
1
0

0

5
10
Viable cell volume (mL)

Advanced measurementson these Bioreactors:• BIOSTAT ® B

It can be used for event-based automation,such as bleed control, feed control, as well as
harvest point and infection point detection.

50®

• BIOSTAT B-DCU®

15

Process understanding requires monitoringof critical process parameters, such as viable
cell density. However, manual sampling
reduces the bioreactor volume, is laborious
and increases the contamination risk. BioPAT ®
ViaMass measures the viable cell volume inline
without the need of sampling and without
contamination risk.

51

Fully integrated SU sensor

k Ease of use, no contamination risk

• BIOSTAT RM

55

Available as reuseable probe for benchtop bioreactors k Covers all scales of process development• BIOSTAT STR®

58

Feedback loops easily establishedk Automated process control, such as cell bleed
or feeding

Biocapacitance is selective to viable cells

k Direct access to viable cell volume

74

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Automated Cell Bleed in Intensified
Processes Through BioPAT ® ViaMass

Viable biomass is one of the most importantcritical process parameters in upstream
bioprocesses. For accessing biomass inSartorius BIOSTAT ® bioreactors, we offer
BioPAT ® Viamass, a capacitance sensor thatmeasures viable cell volume. BioPAT ® Viamassdelivers special value for intensified processing in SU bioreactors. While intensified processing delivers the advantage of increased
productivity, they come with the challenge ofbeing much more complex than conventional
processes and require tighter monitoring andcontrol.
BioPAT ® Viamass can be used to automate
cell bleed in perfusion cultivations. The graphs
to the right demonstrates a perfusion cultivation with automated cell bleed based on the
online ViaMass® signal, performed in BIOSTAT ®
RM system. The viable cell density could becontrolled at 30 million cells per mL in a
fully automated fashion. The product yieldwas 3-fold higher in the intensified processcompared to a conventional fed-batchprocess.

Source: Sartorius R&D Bioprocessing USP –Gerhard Greller, Jens Matuszczyk and Johannes Lemke

75

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

8. Process Analyzers and Sensors

BioPAT ® Trace
Inline Glucose and Lactate Measurement

Learn more about the
®
Learn
about
the
Trace
as glucose
BioPATmore®
Trace
as glucose
BioPATand lactate
sensorand lactate
sensorOverview
Weblinks
124

Applications• 24|7 glucose and lactatemonitoring without volume
loss• Enables automatedfeed control• Capable of low glucose
control (<1g/L) with asampling rate of up to
30 per h

BioPAT ® Trace is a glucose and lactate sensor capable of inline integration into bioreactors.
The measurement principle is a biosensor based on glucose and lactate oxidase generating
an amperometric signal. BioPAT ® Trace probes make use of a dialysis principle, which does not
require sampling.

Advanced measurementson these Bioreactors:• BIOSTAT ® B

50®

• BIOSTAT B-DCU

51• BIOSTAT ® Cplus

66• BIOSTAT D-DCU®

67

76

The glucose concentration in an upstream
process is one of the most relevant criticalprocess parameters in biopharma manufacturing. Too little glucose results in starvation,
while too high levels result in lactate generation, which affects the pH and inhibits cell
growth. Furthermore, it has been shownthat keeping the glucose concentration stable
positively affects product glycosylation.

Manual glucose control based on sampling ishighly laborious, comes with contamination
risks and is often too infrequent to achieve
stable control. BioPAT ® Trace can measure andcontrol glucose and lactate concentration in
an automated fashion without volume loss
with an accuracy of 0.1g/L.

24|7 glucose and lactate monitoring & control

k Working range 0.1 – 20 g/L glucose, accuracy 0.1 g/L

Capable of low glucose control below 1 g/L

k Low glucose control can increase mAB titer by 30%

Biosensor based on glucose and lactate oxidase

k Unparalleled level of glucose control

Inline dialysis sampling without volume loss

k Safe operator time, reduce contamination risks

Self-calibrating during the process;available for BIOSTAT ® single-use and benchtop
bioreactors

k Easy to use system

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

8. Process Analyzers and Sensors

BioPAT ® Fundalux
Inline Monitoring of Total Biomass

Implement a continuous
Implementa continuous
OD600 measurement®
OD600
measurement
Fundaluxwith BioPAT®
Fundalux
with
BioPAT
Overview Weblinks
124

Applications• Inline monitoring of total

biomass based on turbidity
e.g., in microbial cultures• Inline and continuous
OD600 measurement(BioPAT ® MFCS required)• For stainless steel and glass
vessels

The BioPAT® Fundalux system is based on an integrated absorption-based probe using near infrared
light for turbidity measurement. It can be used in all glass and stainless steel bioreactors.
Especially in microbial culture, manual
sampling can be highly time-consuming andinconsistent. The BioPAT ® Fundalux probe
continuously monitors cell growth in yourculture by measuring the turbidity in adefined optical path based on near infrared
light. This inline turbidity measurement canbe correlated directly to laboratory analysis
methods for cell count and OD600 opticaldensity.

The BioPAT ® Fundalux amplifier comesintegrated into BioPAT ® DCU.
Automatically converted the turbidity readingof a Fundalux sensor into an OD600 readingby combining it with BioPAT ® MFCS.

Advanced measurementson these Bioreactors:
BIOSTAT ® bioreactor integration

k All-in-one BioPAT ® DCU, data collection and control

12 and 25 mm probe connectionk Flexible entry into your fermenter

Range of optical path lengths (1, 5 and 10 mm)

k Optimal total biomass coverage for your bioreactor

Online OD600 measurement in combination
with BioPAT ® MFCS

k Provides real-time knowledge to optimize
bioprocess runs
k Makes sampling for OD600 measurement redundantReliable, continuous inline measurementk Eliminates laboratory samplingk More sensitive & cost-effective than offline
sample data

• BIOSTAT ® B

50®

• BIOSTAT B-DCU®

• BIOSTAT Cplus

51
66

®

• BIOSTAT D-DCU

67

77

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

8. Process Analyzers and Sensors

BioPAT ® Xgas
Online Off-Gas Analysis of O2 and CO2
Develop perfusion feeding
Developperfusion
feeding
strategies
facilitatedstrategies
Xgas
by BioPAT ®facilitated®
Xgas 124
by
BioPAT
Overview
Weblinks

Applications• Development of perfusion

feeding strategy based
on OUR• Batch record of % O2 | CO2
in off-gas• Automatic calculation of
metabolic data
• Optimization of microbial
and high cell density cell
culture processes• Measure critical processparameters for scale-up

The compact BioPAT ® Xgas precisely tracks changes in respiratory gas emission from acultivation vessel. It can be integrated as an option into all BIOSTAT ® bioreactors for real-time
calculation of metabolic data, such as oxygen uptake and carbon dioxide emission rate.
The precise measurement of input andoutput metabolic gases by mass flow
controllers and offgas analysis yields insights
into critical metabolic changes during thecultivation process.

This enables the user to apply reliable,
advanced gassing or feeding strategies toimprove production rates and reduce
cultivation time. Develop a perfusion feeding
strategy in one go, facilitated by BIOSTAT ®
B-DCU and BioPAT ® Xgas.

Standardized integration into all BIOSTAT ® bioreactors k All-in-one BioPAT ® DCU, data collection and control
Advanced measurementson these Bioreactors:• BIOSTAT ® B

50• BIOSTAT ® B-DCU• BIOSTAT STR®

51

k Reduces footprint and exhaust piping requirements
k Analyzes O2 enrichment and CO2 headspace gassing

Automatic moisture and pressure compensation

k The highest accuracy and precision ensured

Compact, mountable design

k Safe, ergonomic and space-saving in lab andproduction areas

Fast and easy 1-point calibration to air

k Less time needed for initialization and setup

58• BIOSTAT ® Cplus

66• BIOSTAT D-DCU®

67

78

Parallel measurement of O2 and CO2 by one sensor
Wide detection range

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

AppendixIntroduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

8. Process Analyzers and Sensors

BioPAT ® Pressure
Inline Pressure Measurement

Applications• Monitor pressure controlled

processes, e.g. perfusion
or cross-flow filtration• Detection of filter fouling• Guarantee appropriate backpressure during washing
step in preparation for filter
integrity testing

The BioPAT ® Pressure sensor combines a multi-use transmitter and a single-use flow pipe.
The new design allows for more flexibility, with better longevity, handling and accuracy
The BioPAT ® Pressure sensor uses piezoresistive effect to accurately and quickly determine the pressure inline. The single-use
pipes can be integrated into any assembly(from ¼" up to 1" inner diameter) and include
a fixing mechanism for easy and robust
coupling of to the multi-use transmitter.

80

Once both are assembeld together themeasurement can take place. The pressure
sensor measures reliably over a wide
temeprature range (4 – 40°C) thanks to apre-programmed temperature compensation.
The analog outlet signal (4 – 20 mA) can bedirectly transmitted to a control untit orshown in a benchtop display.

Single-use flow pipe:• Integrated fixing mechanism• Chemical resistancek Easier installation and reliable connection
to transmitter

One transmitter for all sizes

k Appropriate for ADC applications

Factory adjustment procedurek Flexibility in the process scale

Benchtop display

k Higher accuracy
k For at-line monitoring of the flow rateor not controlled stand-alone applications

Multi-use electronics

k No electronic waste

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

8. Process Analyzers and Sensors

BioPAT ® Flow
Inline Flow Rate Measurement

Applications• Monitor flow rate in any

inlet or outlet streams• Determine total volume

of liquid transfered

The BioPAT ® Flow sensor is the world's only ultrasonic flow sensor that combines
a multi-use clamp-on and a single-use flow pipe. This combination assures highest
accuracy and flexibility.
The BioPAT ® Flow sensors use the ultrasonictransit-time technology to accurately andquickly determine the flow rate. The singleuse pipes can be integrated into any
assembly (from ¼" up to 1” inner diameter),independent of the tubing type and without
introducing bends or changing the innerdiameter. Once the multi-use clamp-on isassembled around the pipe, the measurement
can take place.

The effect of temperature is accounted forby using three standard calibration tables,
which cover 4 – 37°C. The measurement is notaffected by the viscosity of the fluid or thepressure of in the system. Data read-out canbe done with a benchtop amplifier box ora DIN-Rail module suitable for electricalcabinets. Both analog (4 – 20 mA) and digital(RS-232) signals are available as output.

Single-use flow pipe:• Precise and straight flow path• Hard plastic with thermoplastic elastomer
overmolding• Fixed measurement position• Chemical resistancek Higher reproducibility and accuracyk Pressure independent measurement withoutcompromising on coupling quality
k The calibration is independent of the type of tubing
and minimizes operator errors
k Appropriate for ADC applications

Multi-use electronics

k No electronic waste

Analog and digital outputs

k Interface flexibility for integration into control unit

Benchtop amplifier box

k For at-line monitoring of the flow rate or notcontrolled stand-alone applications

81

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

9. Process Automation

Automation is Key
Process Automation is one key component to ensure consistency and reproducibilityof bioprocesses.
Local control on the single unit-operation does not stand alone and integration ability is key.
The basis of an integration with ease is heavily relying on a thorough S88 implementation.
Furthermore recipe management to build time & condition based decision are important
modules to reach the required consistency. Embedded in the recipe execution, user guidance
reduces human error during setup of consumables & process execution.
Based on customer specific process & set-up, Sartorius offers a range of solutions,starting with purely out of the box instruments to highly customized solutions well integrated
in customer's IT network.

82

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

9. Process Automation

Standard
Digital Control Unit (DCU)
The Digital Control Unit (DCU) is Sartorius standard for local control automationfor BIOSTAT ® bioreactors. It is well recognized in the industry for its ease of use andintuitive HMI interface.
Furthermore DCU is fast and easy to implement, so the customer is ready to start
the process right away under control of an efficient and GMP ready automation.
Also the extension of the DCU with BioPAT® MFCS SCADA solution is plug-and-play.
Doing so, customer's process is now empowered with batch management, historization,
trends and report, rich GMP ready features and a powerfull S88 advanced recipemanagement.

AdaptedAdapted Modular Process Units
In cases, where standard solutions can not cover custom specific requirements,
Sartorius can offer solutions, which adapt hardware, consumable and automation
to the specific process.
Based on 300+ projects executed, Sartorius offers an automated system composed ofwell tested standard functions with customized changes, to allow faster project execution and robust system in comparison to other engineering approaches.
Fully supported by industrial components and software (Siemens); connectivity to
SCADA, DCS & historian systems are available out of the box hence enabling either standalone process unit as well as a fully integrated solution in the existing infrastructure.
GMP and data integrity requirements are met by a consistent and documented
engineering approach and proven GMP functionality (e.g. user management andbatch reporting).

Customized
Automation Consistency From Sensor to Batch
If your brownfield or greenfield installation requires automation consistency down
to the field level (sensors & actuators), Sartorius will provide a full native solution
together with local partners. Common automation systems are based on Emerson andRockwell, but other can be arranged on request.
In this approach, very specific requirements of installation, automation and process
request can be realized.

83

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

9. Process Automation

BioPAT ® MFCSSCADA Software for Reliable Data
Acquisition, Monitoring and Control
Learn more about
®
Learn
about
MFCS
BioPATmore
BioPAT ® MFCS
Overview Weblinks

124

Applications• Reliable data acquisition,

monitoring and control• For upstream and down-

stream unit operations,e.g., BIOSTAT ® bioreactors,
Sartoflow® and FlexAct®
systems• Across all scales from earlyprocess development tocommercial manufacturing• Incorporating Sartorius and3rd party equipments

BioPAT ® MFCS is the central platform for your online and offline process and analytical data,from cell line and process development to production scale.

SCADA

Supervisory Control
And Data Acquisition

Designed as a “plug-and-play” solution,
it is ideally suited for capturing, storing andvisualizing process data of our Sartoriusbioreactors and other process equipment
including 3rd party units. This software
enhances your ability to build your own
SCADA network using our preconfigured
and bioprocess optimized solution.

The advanced 21 CFR Part 11 compliant
BioPAT ® MFCS suite is a feature-rich, GAMP
category 4 software package capable ofsupporting the most demanding research or
production environment. Besides the corefunctionality of a full-fledged SCADA system,
BioPAT ® MFCS in combination with the
BioPAT ® DCU is the most cost-effective
and flexible platform specifically tailoredfor bioprocessing applications.

Advanced measurementson these Bioreactors:• BIOSTAT ® A®

• BIOSTAT B

49
50

®

• BIOSTAT B-DCU

51• BIOSTAT ® RM

54

• BIOSTAT STR®

58

• BIOSTAT ® Cplus

66• BIOSTAT D-DCU®

67

84

Scalable software for nearly all bioprocessapplications

k Reduced training efforts and improved data consistency

Fully user configurable and upgradable with specificmodulesk Unique customization level and flexible investment
costs

Proven track record of over 25 years applicationin bioprocess development and production

k Reliable and robust system performance

Installation, configuration, validation andengineering services

k Technologically and economically optimized solutions

Central platform for real-time and historical analysis
of process, analytical and sampling data

k Full transparency and accessibility for advanced
process control and understanding

Microsoft® and Windows® are registered trademarks of Microsoft Corporation, USA.

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Seamless Scalablity and Data
Consistency with BioPAT ® MFCS
Seamless scalability, integration of chemometrics tools and consistent controls across all scales
for accelerated process development and process transfers.

Process Development
and Optimization
Cell Line Development

DOE

Design ofExperiments

MVDA

Multivariate
Data Analysis

Data
DOE

Design ofExperiments

Data

Data | Recipe

Data | Recipe

Clinical Trial
Manufacturing

MFCS

Commercial
Manufacturing

MVDA

Multivariate
Data Analysis

Data | Recipe

Process Characterization
and Robustness Testing
MVDA

Online Multivariate
Data Analysis

DOE

Design ofExperiments

MVDA

Multivariate
Data Analysis

85

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

9. Process Automation

Software Modules
BioPAT ® MFCS
Your Choice for Advanced Features
Specialized for bioprocesses, BioPAT® MFCS provides preconfigured modules enabling plug-andplay setup of advanced SCADA functionalities, saving you in-house resources for engineering,
maintenance and training. BioPAT® MFCS and its advanced modules were strictly developed
according to a sustainable software lifecycle design. As a result, you will receive high-quality software for safe and worry-free operation – every time, all the time. These software modules arecompatible with the latest off-the-shelf hardware and software technology.

Connectivity
When today's automation challenge isnative connectivity and interoperability,
BioPAT ® MFCS provides a flexible
Plug&Play device connectivity with
Sartorius equipments, true interoperability
with major third-party softwares and full
support of the OPC Standard to enable a
24 | 7 monitoring of your processes.
Network
MFCS can run a single unit process system
to 24 process units with multi-clients
installation. This is ensured by the MultiUser Option that brings virtualization and
RDS support reducing IT maintenance,
securing the system and bringing remoteavailability.
S88 Recipe Control
Reproducible batches are a must-have forprocess development and pilot manufacturing. The ANSI | ISA-88 compliant Recipe
Control Module for BioPAT ® MFCS enables
this by easy configuration of recipes
following automated batch execution.
21 CFR Part 11
Meeting cGMP and 21CFR part 11
requirements is complex and crucial inbioprocessing. BioPAT ® MFCS 21 CFRpart 11 module supports you with user
management, audit trail, electronic signatures and reporting capabilities bringing
all features to achieve full compliance.

86

Optimization
The BioPAT ® MFCS DOE module will ease
your start into Design of Experiments,
supported by user-friendly wizard guidance. Automatic transfer of the experimental design into a specific recipe allows
for reliable and seamless integration into
existing control strategies.
Analysis
The BioPAT ® MFCS MVDA module supports
easy and fast multivariate data analysis –saving you cumbersome and error-pronetransfer of your process data to standalone software tools for statistical analysis.
Trainings
Join Sartorius training program for
BioPAT ® MFCS! Different level of trainings
will give the necessary practical skills toperform the work safely and efficiently
with BioPAT ® MFCS. On site trainings
can also be adapted to special needs andhelp the user get up to speed with
BioPAT ® MFCS!
Service & Support
Benefit from our international andexperienced service team that offers
a wide range of services including
installation and configuration, computer
system validation (CSV), hotline, remoteand onsite maintenance.

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

10. Chemometrics

Umetrics® Chemometrics
Toolbox
New Opportunities for Efficient
Bioprocess Development and Manufacturing
Take advantage of the Chemometrics
Toolbox and integrate the capabilities
of advanced multivariate methods into
your existing process control software
BioPAT ® MFCS | win.

SCADA

BioPAT ® MFCS

MVDA Module

DOE Module

DOE

OPC Module

MVDA
Design ofExperiments

MVDA

Multivariate
Data Analysis

Online Multivariate
Data Analysis

DOE

MVDA

MVDA-online

Identify critical processparameters and their optimal
ranges and estimate a design
space

Identify normal operation
space and understand reasonsfor process upsets, preparemodels for real-time monitoring in SIMCA-online.

Monitor the manufacturing
processes in real-time andsave batches by early fault
detection

Umetrics® MODDE®

Umetrics® SIMCA®

Umetrics® SIMCA®-online

87

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

10. Chemometrics

Umetrics® MODDE®
DOE – The Efficient Way ofBioprocess Optimization

Applications• Optimization of cell andmicrobial culture media
composition and feed
strategies• Screening and optimizationof process parameters• Design Space Estimation(DSE) and validation

Umetrics® MODDE® is a state-of-the-art Design of Experiments software package that will help
you understand complex processes and products.

DOE

Design ofExperiments

88

Umetrics® MODDE® enables rapid processoptimization with a reduced number ofexperiments. Forget time-consuming,
traditional trial- and error optimization.
You will benefit from unique design spacetools to visualize the most reliable operating
range for the investigated parametersconsidering risk analysis specifications.

Use the Umetrics® MODDE® software to speed
up your development work, to increase
productivity and elucidate primary effects
and interactions of potential critical processparameters and critical quality attributes.

Visual user guidance with a multitude ofautomated functions

k Tool for beginners and experienced users alike

User-friendly design and one click analysis wizard

k Easy setup and reliable data evaluationof experiments

Graphic-rich presentation of results and reports

k Decision-making based on statistically verifiedstatements

Unique connection to BioPAT ® MFCS

k Reliable and seamless integration of DOE procedures
into existing control strategies

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

10. Chemometrics

Umetrics® SIMCA®
MVDA – Discover Hidden Process Information

Applications• Analyse and identify reasonsfor process deviations andupsets• Classification of batches andprocess predictions• Scale and batch-to-batchcomparisons• Identification of key trends,
correlations, patterns,
and relationships in yourprocess data

Multivariate Data Analysis (MVDA) with Umetrics® SIMCA® supports and unlocks process
understanding to ultimately improve the manufacturing consistency and secure throughput
by identifying process behaviour that causes risks.
For many years, Umetrics® SIMCA® has been
the standard tool for scientists and engineers,
enabling them to manage considerable
amounts of data. Umetrics® SIMCA® enables
you to effectively explore your data, analyze
your process and interpret the results.
Use Umetrics® SIMCA® to transform data into
information, allowing you to make the rightdecisions – quickly and confidently.

The unique Umetrics® MFCS MVDA moduleis specifically matched to communicate withand deliver data to Umetrics® SIMCA® in orderto reduce effort associated with data
management and comparison of current
and historical batches.

Easy interpretation and analysis of large processdata sets

k Improved process performance resulting in yield
improvements and impurity reduction, among otherbenefits

Tech-transfer and batch-to-batch comparisonsk Generate process understanding to ultimately
improve the quality, safety and efficacy of yourdrug productSummary of all process information,
all in one data modelk Control and assurance of overall process andproduct quality

Unique connection to BioPAT ® MFCS

k Reduce the effort of data management and transfer

MVDA

Multivariate
Data Analysis

89Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

10. Chemometrics

Umetrics® SIMCA®-online
Manufacturing Intelligence Simplified

Applications• Early fault detection• Golden batch comparison• Real-time multivariate

statistical process monitoring

Umetrics® SIMCA®-online software performs real-time multivariate monitoring of yourmanufacturing processes and provides effective tools for early fault detection and diagnosis.

MVDA

90

Online Multivariate
Data Analysis

Umetrics® SIMCA®-online uncovers hidden
information in your processes. It is a highly
efficient software tool for real-time processmonitoring and control. Predictive analytics
and soft sensor models can be applied using
process parameters and spectral data.

Supplied with data from BioPAT ® MFCS,
this software permits identification ofinconsistencies before they result in a process
deviation and provides user guidance toidentify potential root causes. This resultsin enhanced control and assurance of youroverall process and product quality.

Early detection of process deviations withguidance to identify potential root causes

k Save batches before they reach a critical stage,
reduce cost of goods if batch cannot be saved.
k MVDA identifies inconsistencies in process behavior
earlier than univariate monitoring.

Process trajectories for real-time process monitoringk Enhanced process reliability due toeasy-to-understand graphics

Standard interface to BioPAT ® MFCS via OPC

k Easy implementation into existing IT infrastructures

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

10. Chemometrics

ambr® clone selection
powered by Umetrics®
Software for Consistent Screening
and Ranking

Learn more about the
Learn
the
clone about
selectionambr® more®
clone
selectionambr
softwaresoftwareOverview Weblinks 124

Applications• A new standalone software
application for use with datafrom ambr® 15 and ambr®
250 systems• ambr® clone selection
simplifies the data analysis
workflow for cell line
screening and ranking• ambr® clone selection canalso be used for strain,
media and feed screening
and ranking

ambr® clone selection is a new standalone software application for use with data from ambr® 15
and ambr® 250 systems to simplify the data analysis workflow for cell line screening and ranking.
Users define the selection criteria such as celldensity, product titer and key product quality
attributes and assign priority weightings inorder to screen and rank clones.

The software application uses a uniquemultivariable desirability assessment feature
for clone ranking.

Automation of the clone selection process

k Improves speed and consistency, frees up scientist time

Selection criteria profiles can be stored and sharedwithin the same server

k Can be applied to new data sets for consistentselection by other team members

A report is generated to record the selection criteria
and details of the selected clone candidates

k Possible to view and understand the selection
comprehensively

Re-evaluate at any time

k If selection criteria change during your project, it isfast and straightforward to run the calculation again.

Data can be mined to the full to extract many
key insights®

k Maximizes use of data from ambr experiments

Advanced functionality forthese ambr® bioreactors:• ambr® 15 cell culture38®

• ambr 15 fermentation®

39• ambr 250 high throughput®

• ambr 250 modular

42

46

91

Introduction

Applications• dgdsfgafg

92

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

11. Training Software

BIOSTAT ® T
Virtual Bioreactor Training Tool

Click here to request a
Clickheresoftwareto requestapersonal
licensepersonal
software124
licenseOverview Weblinks

Applications• Virtual training on
BioPAT ® DCU functionality
and controller settings
based on real process data

The BIOSTAT ® T is an interactive software training tool and ideally suited to educate
students and operators in bioprocess control. It enables users to learn about bioprocessengineering and to practice with menu navigation and control of a bioreactor prior tooperating an actual bioreactor.
The BIOSTAT ® T mimics the human machineinterface and functionalities of a single-use or
stainless steel bioreactor. It is based on actual
cultivation batch data data that were collectedunder normal process conditions. This database enables the software to derive cell
growth curves for the mentioned process
conditions algorithmically.

The software enables users to gain insights
into the characteristics of a CHO or Yeast
cultivation. Users have to utilize the broad
variety of software features to determine
the optimal parameters for cell growth andantibody yield.

Integrative learning

k Theoretical principles of bioprocess engineering
can be applied and verified

Close to reality

k Based on the human machine interface ofa single-use or stainless steel bioreactor andcontains real cultivation data

Completely virtual introduction to the operationof a bioreactor

k Achieving high quality results when using a bioreactor
in real life from the very beginning

Time and cost saving

k Risk mitigation of human error and the prevention ofbatch losses

93Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

12. Instrument Services

Sartorius Services for
Maximized Process Security
Keeping a biopharmaceutical process robust and reliable, Sartorius provides a comprehensive
range of services to ensure the highest reliability and uptime of your equipment, regulatorycompliance and best quality of results. From installation and qualification to regularpreventative maintenance: The instrument service team will be happy to assist customer on site
and will be with him quickly thanks to the worldwide service network.

Key Benefits• Process stability andminimized downtime• Maximized system uptime,higher profitability• Optimized total costof ownership

94

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

AppendixService Contracts for the Entire System Lifecycle
With the Bioprocess Service Program, Sartorius offers service contracts to protect customer's
equipment through its entire lifetime. Based on the specific risk assessment and requirements,
customers can choose between three Service Level Agreements: Essential, Advanced andComprehensive. Protect equipment by choosing the appropriate service contract.
For maximum productivity and minimum downtimes.

Reaction time
Reaction time
Reaction
Reactiontimetime

Repair

h
h

h

h

hhh

hhh
h

h

hhh

RepairRepairRepair

h
hh hh
h

hh
Maintenance
Maintenance
Maintenance
Maintenance

Essential Essential Essential
Essential
Advanced Advanced Advanced
Advanced
Comprehensive
Comprehensive
Comprehensive
Comprehensive

Essential
Benefit from:

Advanced
Benefit from:

Comprehensive
Benefit from:• A plannable annual maintenance• A fast support at the technicalhelpdesk within one business day
and priority on-site-response• In case of repair:A discount on all time andmaterial based cost elements• A plannable annual maintenance• Technical helpdesk reaction timewithin 8 hours and 72 hours
on-site response• In case of repair: labor and travel
costs are covered, a discount of
10% on spare parts• A plannable annual maintenance• Technical helpdesk reaction timewithin 4 hours and 48 hours
on-site response• In case of repair: all costs arecoveredFor further details and the dedicated datasheets,
website:please have a look at our website.
www.sartorius.com/service95Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

﻿IV. Clarification

96

1. Automated Cell Removal | Supernatant Clarification

98

2. Cell and Contaminant Removal with Depth Filters

99

3. Centrifugation Systems

100III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix﻿97Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

1. FlexAct® Single-use Automated Cell Removal | Supernatant Clarification

FlexAct® Solution
Single-use Automated
Cell Removal | Clarification

Learn more about
®
Learn
about
Solution
FlexActmore®
Solution
FlexAct
Overview Weblinks 124

Applications•	Automated mammalian cell
removal from productionbioreactor•	Clarification of bioreactor
supernatant for capturecolumn loading• Post centrifuge filtrationof supernatant

The FlexAct® configured to order solution brings together hardware, software,
wetware and documentation into a ready to produce package for single-use bioprocessing.
Cell Removal | Clarification enables the directprocessing of a 2,000 L bioreactor in a single
8 hour shift. It uses pre-defined configurable
software based on ANSI | ISA-S88 industrial
standards for batch processing.

The modular FlexAct® build and connectionof sensor, actuator and holder components
allows them to be shared between unit
operations, enabling a single FlexAct® system
to perform up to 6 distinct unit operations
at various volumetric scales.

The software architecture allows easyinterface to Distributed Control Systems(DCS) for plant-wide integration.

98

Flexible processing skids with multiple functionality
for diverse unit operations

k Supports multi-product | adaptive-scale bioproduction

Easy to integrate into distributed control
systems and manufacturing execution systems

k Speed and effort of system integration

Easy-to-use predefined application software
based on flexible unit operation recipes

k No additional coding or programing of software

Reliable Single-Use sensor and actuator technologies

k Higher process accuracy and control

High degree of automation, user guidance,system diagnostic and process transparencyk A reduced risk of error and unplanned downtime

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

2. Cell and Contaminant Removal with Depth Filters

Sartoclear® Depth Filters
Cell and ContaminantRemoval Technologies
Learn more about
Learnmore® Depth
about Filters
Sartoclear®
Depth124
Filters
Sartoclear
Overview Weblinks

Applications• Clarification of moderate
cell density cultures(<5% wet cell weight)• Post centrifuge filtration• Mammalian cell culture
harvests• Microbial lysates• Removal of precipitatesfrom sera and plasma• Particle and colloid removalfrom process intermediates

Sartoclear® filters are cellulose-based depth filters developed for demanding clarification
applications in the biotechnological and pharmaceutical industries. Cellulose based depth
filters protect subsequent membrane filters from premature blockage by retaining particles
and contaminants originating from the host organism.
The wide range of grades offers a solution
for a variety of applications such as post
centrifuge filtrations, perfusion processes,
and direct harvests with moderate celldensities.

Various filter sizes and formats are available
to meet the process requirements from early
development throughout clinical phases andup to large scale manufacturing while always
keeping the same filter material.

Big variety of device formats

k Serves customer from the lab up to large scalecommercial manufacturing with the same
depth filter grade

Three different sizes per gradek Linear scale up & flexible filtration areas

Availability in double layer and single layer formats

k Easy optimization with different applications

Lower pre-flushing volume ( 50 L/m2)

k Reduces costs, water | buffer and saves time

Use the same accessories to run two depth filter
grades in series

k Run primary and secondary clarification in one step

Ergonomic design

k Safe and easy dismantling of filled cassettes

99Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Centrifugation Systems

kSep® Systems
Robust & Scalable
Single-Use Centrifugation

Learn more about
Learn
morecentrifugation
about
single-use
single-use
centrifugation
Overview
Weblinks
124

Applications• Harvest | Clarification• Cell Therapy• Vaccine Manufacturing

Sartorius kSep® systems provide robust, single-use bioprocessing solutions in the areasof recombinant therapeutics, cell therapy, vaccine manufacturing, and blood processing.
kSep® systems solve the problems of
traditional centrifugation and filtration based
technologies by handling very high celldensities while providing high recoveries
and product quality.

100

Patented kSep® systems technology is
the only current technology that provides
significant advantages for users that wantto either harvest cells as product or discard
cells as by-product during manufacturing.

Only bowl centrifuge that does not stop rotating
while discharging

k Integrates and | or reduces processing steps and timeThrough the balance of centrifugal and fluid flow
forces, the kSep® retains particles such as cells
or microcarriers, as a concentrated fluidized bed
under a continuous flow of media or buffer.

k Constant cell viability due to low shear

The system can be operated under sterile
Conditions.

k All consumables are delivered pre-sterilized

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

AppendixIntroduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

﻿V. Bioanalytics andBiosafety102

1. Product Characterization and Biosafety Testing Services

102

2. Bioanalytics

108

3. Virus Quantification

109

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix﻿103Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

1. Product Characterization and Biosafety Testing Services

Product Characterization andBiosafety Testing Services
Physicochemical and Biological Analytical
Comparability for Biosimilars
Demonstrating biosimilarity is a complex process that presents some unique challenges
for developers and manufacturers. As an industry leading expert in supporting biosimilar
development, BioOutsource offer a comprehensive testing package including structural,
physicochemical and biological analysis. Our testing package includes off-the-shelf assays
and platform methods to deliver cost efficiences and reduce development timelines.

BioOutsource partner with biosimilar clients at the following stages of drug development:
Cell Line
Development

Clone
Selection

Process
Optimization

Process Characterization

Product Characterization

Comparability

Commercialization

BioOutsource offer a variety of methods to support the testing of a wide range of biosimilar
monoclonal antibodies including:• Herceptin (trastuzumab)• Remicade (infliximab)• Humira (adalimumab)• Simponi (golimumab)• Enbrel (etanercept)• Stelara (ustekinumab)• Avastin (bevacizumab)• Prolia (denosumab)• Lucentis (ranibizumab)• Actemra (tocilizumab)• Rituxan (rituximab)
Currently, in our R&D pipeline we are developing methods to support assessmentsof biosimilarity for the following molecules:

104• Erbitux (cetuximab)• Opdivo (nivolumab)• Synagis (palivizumab)• Tysabri (natalizumab)• Eylea | Zaltrap (aflibercept)• Yervoy (ipilimumab)• Xolair (omalizumab)• Orencia (abatacept)

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

Fab Binding

Fab Functional– ELISAs (Indirect,
Competition,
Blocking, Cell Based)– FACs– SPR– Various Direct,
Blocking,
Neutralising MOAs

VI. Application and Engineering Services

Appendix

AntigenBinding

Structural &Physicochemical
Fab– Molecular weight– Charge variants– Carbohydrate
structure (glycans)– Peptide mapping

Fc Binding

Fc Functional– C1q (ELISA)– FcRn– Fcγ Receptors– ADCC– Surrogate ADCC
– CDC

Fc

Key Benefits
Speed• Reduce assay development time byaccessing BioOutsource’s off-the-shelfassaysCost Reduction• Reduce assay development costs using
off-the-shelf assays
Technical Expertise•	Leverage BioOutsource’s experience ofworking with over 50 biosimilar developersQuality•	Greater quality assurance with sensitive
methods and comprehensive data reporting
Regulatory•	Excellent regulatory insights for generating
data required for regulatory submissions
 esearch & Development
R•	In-house R&D team works closely withclients to ensure that new methods arereadily available for the next generationof biosimilars

105Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

1. Product Characterization and Biosafety Testing Services

Physicochemical andBiological Characterizationof Novel Biological Entities
Our off-the-shelf Targets
We have extensive expert knowledge tosupport your New Biological Entity (NBE)
with our off-the-shelf & custom assays, aswell as regulatory compliant biosafety testingin the following areas:

Our Approach = Your Success
Speed	Faster assay development
to shorten your timeline IND
submission• Bioassays

Flexibility• Cell-based Potency Assays

Expertise 	Extensive experience &full range of platform
methodologies• Binding Assays• Physicochemical & Structural Analyses• Qualification & Validation

Compliant 	Fully cGMP compliant
laboratories
Integrated

Customizable
Off-the-Shelf

Development Services

Qualification

Tailored testing packages

Full service package available

Validation

Our method lifecycle approach takes you from pre-clinical development through to phase III
validation and commercial lot release, with a smooth transition to cGMP services from our fullycompliant laboratories.

Early Assay Development &Screening

Structural and Physiochemical
Analytical Package

Analytical Methods Qualification• Custom Assay Development (DoE)• Supporting your development
process from pool | clone
selection -> assessments ofproduct stability• ICH Q6B Specifications:
Test Procedures and AcceptanceCriteria for Biotechnological |Biologcal Products• Methods to meet regulatory
standards• ICH Q2B Validation of Analytical
Procedures• Tech Transfer• Optimization (DoE)106

III. Bioreactors and PAT

V. Bioanalytics and Biosafety

IV. Clarification

VI. Application and Engineering Services

Appendix

Our panel of off-the-shelf monoclonal antibody characterization assays are ready to go
for a range of targets (TNF, CD20, VEGF, HER2, EGFR, PD-1, PD-L1, IgE, IL-12/23, RANKL. etc).
Our assays have been qualified with commercially available innovator mAbs such as Humira,
Rituxan, Herceptin, Avastin etc. – Ask for our qualification reports today.

Fab Binding

Structural Analysis

Fab Functional• ELISA Methods• Flow Cytometry• SPR Methods• LC-MS Methods• N-glycan Analysis• Intact Mass
• Peptide Mapping• Various direct• Blocking• Neutralizing• MOAsFc Binding

Fc Functional• C1q (ELISA & SPR)
• Fcγ Receptor SPR• FcRn• ADCC• ADCP• CDC

Don’t see your target? Don’t worry.
Contact us today to discover our possibilities.

Full Range of Fc Effector Binding& Functional Assays

GMP Method Validation• Protein therapeutics:
Characterization of immunologicaland biological properties• Product specific validation
supporting stability studies& lot release• Experience in Fc characterization
assays including, binding to C1q,
Fc receptors, ADCC & CDC• USP1033, Ph. Eur. & ICH Q2B
specifications

107

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

1. Product Characterization and Biosafety Testing Services

Biosafety Testing Services
Our Capabilities
All biopharmaceutical and biotechnology products must undergo stringent safety testing
throughout development and manufacture to ensure the products and host cell lines
are characterized and free from contamination.

Excellent Technical Expertize
Industry leading expertise inbiosafety testing of biologics
and viral vaccines

Extensive Regulatory Knowledge

Industry Leader

Fast Turnaround Times
Industry leading assay turnaroundtimes

Biosafety Testingof Biologics
and Viral Vaccines

Biosafety testing within the manufacturing
process should be established in the earlystages of drug development. Before clinical
trials, the cell banks (Master, Working,and End of Production) require comprehensive
testing to characterize the bank, demonstrate
purity and confirm that the banks are freefrom contamination and adventitious agents.
We have developed and validated a rangeof assays to characterize cell banks originatingfrom different species including murine,
hamster, human and primates.

Knowledge of testing requirements
for release in Europe, USA, Japanand South Korea

Greater Quality Assurance
Quality driven results. Fully compliant GMP,
GLP and GCP facilities

BioOutsource also supports the testingof bulk harvests and final product and haveexperience working with the following
products:• Biosimilar (monoclonal antibodies)• Recombinant proteins• Viral vaccines• Gene therapy vectors• Oncolytic virus products• Plasma-derived therapies• Cell therapies

BioOutsource partners with clients from early stage development through to commercialization of the product:
Cell Line
Development

108

Clone Selection

Process
Optimization

Process
Characterization

Product
Characterization

GMP Lot Release

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Sterility
Microbiological

Mycoplasma
Mycobacteria

Identity

Cell line identity by
DNA barcoding
In vitro
Adventitious

In vivo
PERT

Viral safety testing

Retrovirus

Infectivity assays
TEM

Biosafety Tests

Genetic analysis

Species specific viruses

MAP & HAP

Sequencing

Bovine | Porcine species
by real time PCRSouthern blot

Human | Simian | Rodent
species by real time PCR

Gene copy number

Endotoxin
Abnormal toxicity
Other key assays

Residual impurities(DNA | HCP | Benzonase)pH, appearance, osmolality

109

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

2. Bioanalytics

Cy-Clone PLUS™ Kit
The Fastest Way to Identifying Clones

Applications• Identifies optimal clones
with more criticalproductivity attributes• Provides fast and easyclone selection• Assesses IgG production
on a per cell basis• Provides cell viability andcount assessment

The Cy-Clone PLUS™ kit along with the iQue3 and and ForeCyt® Software correlates
IgG quantitation per cell with cell health readouts and cell density in a single, cost-effective
assay that can migrate through the entire workflow from screening to scale up.
Cell number is an important variable
to consider when ranking clones. It is helpful
to understand how many cells are producing
the IgG titer to get a better picture ofwhether a particular clone is growing welland whether it is an optimal producer or not.
Assessing IgG production on a per cell basis,in addition to cell density and total IgG
production measurements, gives a muchdifferent picture as to which clones are110

the optimal producers. Cy-Clone PLUS™
multiparametric readout (IgG titer, IgG titer
per cell, cell density and cell viability) offers
more critical productivity attributes from eachclone, a comprehensive assessment of whichclones are healthy and will be the optimal
producers for further evaluation.

Content – More critical productivity attributes
from each clone

k More relevent data, clone numbers, viability,
how the clones are performing

Speed – More clones screened in less time

k Evaluate 3.5 × more clones than legacy methods

Usability – More user-friendly workflow, templated
analysis and easy visualization

k The Profile Map feature in ForeCyt® Software,automatically defines the the desired clones fromuser-defined criteria

Insight – More insight for better clone selection

k Insight leads to actionable results to drive cell line
development forward

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

3. Virus Quantification

Virus Counter® Platform
Biologically-Relevant Total Virus Particle
Quantification
Learn more about®
Learn
more about
Platform
Virus Counter®
Virus
Counter
Overview Weblinks Platform
124

Applications• Optimization of growth

conditions in processdevelopment• Monitor viral titer in nearreal-time• Increased yields andshortened timelines by
harvesting with precision• Early identificationof challenges

The Virus Counter® platform is purpose-built for virus quantification. The instrument,
reagents and software are optimally suited to quantify total viral particles in near real-time.
The Virus Counter® platform offers an
emerging approach to enable direct,
biologically-relevant quantification of virusesin minutes, rather than the days or weeks
required by more historical methods.
The platform features multiple detection
systems, the versatile Combo Dye® reagent
and the antibody-based ViroTag® reagents.
Flow-based, no wash assay

Both approaches use a simple, no wash
workflow to stain virus samples, offering theright solution for individual quantificationneeds. The platform allows users to optimize
growth conditions for viral production,
track viral titers in bioreactors, and precisely
determine optimal harvesting times.

k Unrivaled speed to results

Virus-specific reagents

k Biologically-relevant and specific readout

Direct binding of fluorescent reagentsk Total virus particle quantification

Software-assistend operation and analysis

k Ease-of-Use

111

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

﻿VI. A
 pplication andEngineering Services

112

1. Integrated Process Development Services

114

2. Bioprocess Development & Engineering

116

3. Application Centers118

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix﻿113

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

1. Integrated Process Development Services

Accelerate The Early
Phase Drug Development
Sartorius Process Development
Consultants Guide Through Process Design
Sartorius provides a free process development consultancy service to support the integrationof your early phase development activities ensuring speed to clinic and commercial
manufacturing with robust, cost-effective processes.

Master Cell Bank &Characterization

14 months
4 months
Vectorcloning

Transfection &Pool Generation

Single cellcloningClone
evaluation

Material for
Downstream
Development
E arly material availability helps to frontload
Downstream development and non genericassay development

114

Research Cell Bank
preparation

Downstream
Development

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix“As scientific innovation in healthcare expands rapidly,
biotech companies are aggressively looking
to move their products in to the clinic quickly.
Sartorius’ Process Development Consultants
will advise on an optimal PD strategy
every step of the way and help build a rapidly
scalable process around your molecule.”

Drug Substance& Drug ProductCoA
Confirmationrun

Downstream
Development

Tox
Production

Clinical
Production

115

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

2. Bioprocess Development & Engineering

Flexible, Scalable andCost Efficient Bioprocess
Facility Solutions
Rapid and Flexible Biomanufacturing
The Sartorius Integrated Solutions team works with the customer and designs the entire
biomanufacturing process based on single-use or hybrid solutions. Sartorius delivers andimplements rapid and cost-effective biomanufacturing solutions from early phase development
through scale-up to commercial manufacturing. Benefit from the most comprehensive bio­process technology portfolio coupled with Sartorius' expertise in single-use technologies.
The global bioprocess engineering teams are available to discuss development and manufacturing
requirements.

Bioprocess consultancy services for optimized process design and best technology selection

Approval for
DesignConsulting
Sales

PreConcept

Conceptual
DesignPurchase
Order

Basic
DesignCustomer
AcceptanceProtocolApproval for
FAT

Detailed
DesignProduction

Approval for
Construction

Factory
Acceptance
Test

Installation |Commissioning

Site
Acceptance
Test

Approval for
Shipment

Visit the Integrated Solution Website.
Website:https://www.sartorius.com/en/services/bioprocess-development-engineering
Discover companies who have found success with Integrated Solutions.
From contract
Discovercompanies
manufacturing
who have organisations
found successto
withpharmaIntegrated
companies,
Solutions.
From contract
producingmonoclonal
manufacturing
antibodies,organisations
antibody drug
to pharma
conjugates,
companies,
vaccines or
producingblood
and plasma
monoclonal
products.
antibodies, antibody drug conjugates, vaccines or
blood and plasma products.
Watch Video: www.sartorius.com/video-integrated-solutions

116

Watch Video:
Moving your biopharmaceuticalprocess towards production

Project
Review
Project
Review

III. Bioreactors and PAT

IV. Clarification

VI. Application and Engineering Services

V. Bioanalytics and Biosafety

Customer specific BIOSTAT STR® 2000 Twin design

Appendix

SARTOFLOW® 150 Crossflow System

Over 100 Successful Fully Single-Use and Hybrid Project
Implementations
Mitigate Investment Risks due to Strong Attrition Rates in Bioprocess Development
We design a bioprocess solution with maximum flexibility in mind to facilitate changing
requirements. We tailor our offering around your business scenario along your short and longterm goals. We have experience of process design and engineering from implementing a wide
variety of different products and processes at different scales. With over 100 successful process
implementations we understand the implication on bioprocess design when working withsingle-use and hybrid solutions.

PROCESS

vaccines

mAb

Project execution timeline for a monoclonal antibody process (1000 L, 3 g/L titer)

SUCCESS

Using our mAb process platform approach based on pre-defined solutions,
you reduce engineering efforts and deliver your project at a considerably shorter
timeline compared to conventional stainless steel approaches.

recombinant
proteins

Clinical
Phase

PrePhase
Clinical l

Phase
lI

Phase
lII

Pro­ uctiondDemandof quantity

1 kg

10 kg

20 kg

50 kg

Batch Size

5 kg

50 L until 2500 L

Product Titer
1 g/L
2 g/L
3 g/L
5 g/L
Single-Use Solution

Hybrid or Multi-use Solution

Q1 Year 1

Q2 Year 1

Q3 Year 1

Q4 Year 1

Q1 Year 2

Process Equipment
Pre-Conceptual Design
Conceptual Design Study (URS Definition)
Review | Approval Conceptual Design
Basic Design (URS Finalization)
Detailed Design
Review | Approval Detailed Design
Purchasing Materials
Equipment Assembly | FAT
Packing
Shipment
Customs Clearence | Transport to Site
On-site Installation | Commissioning
SAT
Hand Over• Process4Success (Single-use Platform Process)• Classic Stainless Steel

117

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

3. Application Centers

Visit Your Closest
Sartorius Application Center!
Experience hands-on how our single-use bioprocess solutions work and improve customer
specific operations. Visit one of Application Centers in the USA, Germany or China. For further
information, follow the links below or contact the local sales representative. We are looking
forward to welcoming you soon.

Key Benefits• P rojects can be discussed with Sartorius
experts to identify the best solution forevery specific need based on Sartorius'
broad experience• Look beyond the obvious and see further
systems that might simplify the daily work

• E xperience flexible, reliable and smart
equipment for specific applications

Bohemia, NY, USA

https://www.sartorius.com/en/knowledge/
application-center/application-centernew-york-usa

118

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Goettingen, Germany

https://www.sartorius.com/en/knowledge/
application-center/application-centergoettingen-germany

Shanghai, China

https://www.sartorius.com/en/knowledge/
application-center/application-centershanghai-china

119Introduction

Table of Contents

Latest Trend powered by Sartorius

Appendix

Glossary

120

ADCC

Antibody-Dependent Cellular Cytotoxicity

ASTM

American Society for Testing and Materials

bDtBPP

Bis (2,4-di-tertbutylphenyl) phosphate

CAR

Chimeric Antigen Receptor

CC

Cell Culture

CD

Chemically Defined

CDC

Complement Dependent Cytotoxicity

CFD

Computational Fluid Dynamics

CHO

Chinese Hamster Ovary (cells)

CIP

Cleaning in Place

DCU

Digital Control UnitDNA

Deoxyribonucleic Acid

DOE

Design of Experiments

DSE

Design Space Estimation

FAT

Factory Acceptance Test

FDA

Food and Drug Administration

FPERT

Fluorescent Product Enhanced Reverse Transcriptase

GAMP

Good Automated Manufacturing Practice

GF

Glass Fiber

GLP

Good Laboratory Practice

GMP

Good Manufacturing Pratice

HAP

Hamster Antibody Production

HCP

Host Cell Protein

IQ | OQ

Installation Qualification / Operational Qualification

ISO

International Organization for Standardization

LAK

Lymphokine Activated Killer

LED

Light Emitting Diode

lpm

Litre Per MinutemAb

Monoclonal Antibodies

MAP

Mouse Antibody Production

MCB

Master Cell Bank

MDCKMadin-Darby canine kidney (cells)

MFC

Mass Flow Controller

MLV

Murine Leukemia Virus

I. Cell Line

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

MO

Microbial Culture

MVDA

Multivariate Data Analysis

MVM

Minute Virus of Mice

NIR

Near Infrared

NAO

Non Animal Origin

OPC

Open Platform Communications

PAT

Process Analytical Technology

PBL

Peripheral Blood Lymphocytes

PCR

Polymerase Chain Reaction

PES

Polyethersulfone

PID | P&ID

Piping and Instrumentation Diagram

PLC

Programmable Logic Controller

PPV

Porcine Parvovirus

PTFE

Polytetrafluoroethylene

QbD

Quality by Design

QC

Quality Control

R&D

Research and Development

RAPD

Rapid Amplification Polymorphic DNA

RCB

Research Cell BankRFRadio Frequency

RM

Rocking Motion

rpm

Revolutions per Minute

SAT

Site Acceptance Ttest

SCADA

Supervisory Control and Data Acquisition

SIP

Sterilization In Place

SOP

Standard Operating Procedure

SPR

Surface Plasmon Resonance

SU

Single Use

SV

Solenoid Valve

TEM

Transmission Electron Microscopy

TIL

Tumor Infiltrating Lymphocytes

USP

U.S. Pharmacopeial Convention

WCB

Working Cell Bank

WFIWater for Injection

VI. Application and Engineering Services

Appendix

121

Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

II. Media

Appendix

Solutions for
Downstream Processing Needs
Sartorius offers a wide range of process solutions for purification of monoclonal
antibodies, recombinant proteins, vaccines and antibody drug conjugates.
SCADA system, process automation and chemometrics toolbox

Harvest Single-use
centrifugation Depth filters Sterile filtration

Virus Inactivation

Concentration | Diafiltration

Capture Crossflow filtration Biosafety testing

Buffers  Platformsystem forlow pH virus
inactivation  Crossflow systems
and cassettes  Membraneadsorption
chromato­graphy
solutions Platform systemfor buffer preparation
 Bags for mixing andstorage Ready-made liquidbuffers in bottles andbags

 Production122 Process development & scale-down devices

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

VI. Application and Engineering Services

Appendix

Polishing

Virus Filtration | Clearance

Bulk Drug Substance Preparation  Membrane adsorption
chromatography
solutions  Virus filtration systems
and filters  Crossflow systems andcassettes

Process Development  Freeze-thaw bags

Process Development  Controlled freeze-thaw
solutions  Sterile filters and integrity
testersPre- and sterile filters, integritiy testers, bags for mixing and storage, tubings,
connectors, disconnectors

123Introduction

Table of Contents

Latest Trend powered by Sartorius

I. Cell Line

Appendix

Overview Weblinks

Page Description

Link
®

28

Learn more about FlexAct Solution

https://www.sartorius.com/en/products/process-filtration-purification/
flexact-single-use-automated-solutions

30

Learn more about the Sartopore® 2 Filter Family

https://www.sartorius.com/shop/ww/en/usd/sartopore%c2%ae-2/c/
M_Sartopore_2

30

Learn more about the Sartoguard Filter Family

https://www.sartorius.com/shop/ww/en/usd/sartoguard%c2%ae/c/
M_Sartoguard

31

Learn more about the MaxiCaps® MR

https://www.sartorius.com/en/products/process-filtration-purification/
process-sterile-filtration/filter-transfer-sets/maxicaps-mr

32

Learn more about the Sartocheck® 5 Plus
Filter Integrity Tester

https://www.sartorius.com/en/products/process-filtration-purification/
process-filtration-hardware/integrity-testing/sartocheck-5

33

Learn more about the virus risk mitigation
strategy

https://www.sartorius.com/en/products/process-filtration-purification/
virus-filtration/virosart-media

38

Learn more about the new generation ofambr® 15 cell culture

https://www.sartorius.com/en/products/fermentation-bioreactors/
ambr-multi-parallel-bioreactors/ambr-15-cell-culture

39

Take a tour of the ambr® 15 fermentation
workstation and microbioreactor vessel

https://www.sartorius.com/en/products/fermentation-bioreactors/
ambr-multi-parallel-bioreactors/ambr-15-fermentation

42

Find out about ambr® 250 high throughput

https://www.sartorius.com/en/products/fermentation-bioreactors/
ambr-multi-parallel-bioreactors/ambr-250-high-throughput

44

Read about ambr® 250 high throughput
perfusion

https://www.sartorius.com/en/products/fermentation-bioreactors/
ambr-multi-parallel-bioreactors/ambr-250-high-throughput-perfusion

46

Find out more about ambr® 250 modular

https://www.sartorius.com/en/products/fermentation-bioreactors/
ambr-multi-parallel-bioreactors/ambr-250-modular

49

See how easy it can be to control a bioreactor

https://www.sartorius.com/en/products/fermentation-bioreactors/
benchtop-bioreactors/biostat-a

50

Check out the possibilities of BIOSTAT ® B

https://www.sartorius.com/en/products/fermentation-bioreactors/
benchtop-bioreactors/biostat-b

50

Watch Video on Sartorius
Benchtop Bioreactor Website

https://www.sartorius.com/en/products/fermentation-bioreactors/
benchtop-bioreactors

51

Learn more about the BIOSTAT ® B-DCU
as Perfusion Bioreactor

https://www.sartorius.com/en/products/fermentation-bioreactors/
benchtop-bioreactors/biostat-b-dcu

52

Get more information about the featuresof UniVessel® Glass

https://www.sartorius.com/en/products/fermentation-bioreactors/
benchtop-bioreactors/univessel-glass

53

Turn the production process to single-use

https://www.sartorius.com/en/products/fermentation-bioreactors/
benchtop-bioreactors/univessel-su

54

Learn more about the BIOSTAT ® RM TX forcell therapy applications

https://www.sartorius.com/en/products/fermentation-bioreactors/
single-use-bioreactors/biostat-rm-tx

55

Learn more about the BIOSTAT ® RM as a fully
GMP compliant wave-mixed bioreactor

https://www.sartorius.com/en/products/fermentation-bioreactors/
single-use-bioreactors/biostat-rm-flexsafe-rm

124

II. Media

III. Bioreactors and PAT

IV. Clarification

V. Bioanalytics and Biosafety

Page Description

VI. Application and Engineering Services

Appendix

Link
®

56

Learn more about the BIOSTAT RM 200 rocker
as a large-scale bioreactor

https://www.sartorius.com/en/products/fermentation-bioreactors/
single-use-bioreactors/biostat-rm-flexsafe-rm

58

Learn more about the BIOSTAT STR® bioreactor
familyhttps://www.sartorius.com/en/products/fermentation-bioreactors/
single-use-bioreactors/biostat-str-flexsafe-str

59

Learn more about the Flexsafe STR®
single-use bags

https://www.sartorius.com/en/products/fermentation-bioreactors/
single-use-bioreactors/biostat-str-flexsafe-str

60

Learn more about the Integrity Testingincl. bag test

https://www.sartorius.com/en/products/process-filtration-purification/
process-filtration-hardware/integrity-testing

62

Learn more about the Flexsafe® bag family

https://www.sartorius.com/en/products/fluid-management/liquidstorage-shipping/flexsafe-liquid-storage-shipping

62

Watch Video: New Bag Family

https://www.sartorius.com/en/products/fluid-management/
liquid-storage-shipping/flexsafe-liquid-storage-shipping

66

Learn more about the BIOSTAT ® Cplus
as a laboratory stainless steel fermenter

https://www.sartorius.com/en/products/fermentation-bioreactors/
stainless-steel-bioreactors/biostat-cplus

67

Learn more about the BIOSTAT ® D-DCU
as the fast lane to production

https://www.sartorius.com/en/products/fermentation-bioreactors/
stainless-steel-bioreactors/biostat-d-dcu

74

Learn more about the BioPAT ® ViaMass
as biomass measurement sensor

https://www.sartorius.com/en/products/process-control-data-analytics/
prozess-analyzers

76

Learn more about the BioPAT ® Trace as glucose
and lactate sensor

https://www.sartorius.com/en/products/process-control-data-analytics/
prozess-analyzers

77

Implement a continuous OD600 measurementwith BioPAT® Fundalux

https://www.sartorius.com/en/products/process-control-data-analytics/
prozess-analyzers

78

Develop perfusion feeding strategies facilitatedby BioPAT ® Xgas

https://www.sartorius.com/en/products/process-control-data-analytics/
prozess-analyzers

84

Learn more about BioPAT ® MFCS

https://www.sartorius.com/en/products/process-control-data-analytics/
automation/biopat-mfcs

91

Learn more about the ambr® clone selection
softwarehttps://www.sartorius.com/en/products/fermentation-bioreactors/
software-apps-for-bioreactors/ambr-clone-selection

93

Click here to request a personal software license

https://www.sartorius.com/en/products/fermentation-bioreactors/
software-apps-for-bioreactors/biostat-t

98

Learn more about FlexAct® Solution

https://www.sartorius.com/en/products/process-filtration-purification/
flexact-single-use-automated-solutions

99

Learn more about Sartoclear® Depth Filters

https://www.sartorius.com/en/products/process-filtration-purification/
process-filtration-harvesting/sartoclear-depthfilters

100

Learn more about single-use centrifugation

https://www.sartorius.com/en/products/process-filtration-purification/
process-filtration-harvesting/ksep-systems

111

Learn more about Virus Counter® Platform

https://www.sartorius.com/en/applications/quality-control-testing/virus-quantification

125Sales and Service Contacts
For further contacts, visit www.sartorius-stedim.com

Americas

Asia | PacificGermany
Sartorius Stedim Biotech GmbH
August-Spindler-Strasse 1137079 Goettingen

PolandSartorius Stedim Poland Sp. z o.o.
ul. Wrzesinska 70
62-025 Kostrzyn

USA
Sartorius Stedim North America Inc.
565 Johnson Avenue
Bohemia, NY 11716

Australia
Sartorius Stedim Australia Pty. Ltd.
Unit 5, 7-11 Rodeo Drive
Dandenong South Vic 3175

Phone +49.551.308.0

Phone +48.61.647.38.40

Toll-Free +1.800.368.7178

Phone +61.3.8762.1800

Sartorius Stedim Systems GmbH
Robert-Bosch-Strasse 5 – 734302 Guxhagen

Russian Federation
LLC “Sartorius Stedim RUS”
Vasilyevsky Island
5th line 70, Lit. A
199178 St. Petersburg

Argentina
Sartorius Argentina S.A.
Int. A. Ávalos 4251
B1605ECS Munro
Buenos Aires

Phone +7.812.327.53.27

Phone +54.11.4721.0505

China
Sartorius Stedim (Shanghai)
Trading Co., Ltd.
3rd Floor, North Wing, Tower 1
No. 4560 Jinke Road
Zhangjiang Hi-Tech Park
Pudong District
Shanghai 201210, P.R. China

Phone +49.5665.407.0
FranceSartorius Stedim FMT S.A.S.
ZI des Paluds
Avenue de Jouques – CS 91051
13781 Aubagne Cedex
Phone +33.442.845600
Sartorius Stedim France SAS
ZI des Paluds
Avenue de Jouques – CS 71058
13781 Aubagne Cedex
Phone +33.442.845600
Austria
Sartorius Stedim Austria GmbH
Modecenterstrasse 221030 Vienna
Phone +43.1.7965763.18
Belgium
Sartorius Stedim Belgium N.V.
Rue Colonel Bourg 105
1030 Bruxelles
Phone +32.2.756.06.80
Hungary
Sartorius Stedim Hungária Kft.
Kagyló u. 52092 Budakeszi

Spain
Sartorius Stedim Spain, S.A.U.
Avda. de la Industria, 32
Edificio PAYMA
28108 Alcobendas (Madrid)
Phone +34.913.586.098
Switzerland
Sartorius Stedim Switzerland AG
Ringstrasse 24 a
8317 Tagelswangen
Phone +41.52.354.36.36
U.K.
Sartorius Stedim UK Ltd.
Longmead Business Centre
Blenheim Road, Epsom
Surrey KT19 9 QQ
Phone +44.1372.737159
Ukraine
LLC “Sartorius Stedim RUS”
Post Box 440 “B”
01001 Kiev, Ukraine
Phone +380.44.411.4918

Phone +36.23.457.227

AfricaItaly
Sartorius Stedim Italy S.r.l.
Via dell’Antella, 76/A
50012 Antella-Bagno a Ripoli (FI)Republic of South Africa
Sartorius South Africa (Pty) Ltd
Unit 4, Alphen Square South853 16th Road
Midrand 1685, RSA

Phone +39.055.63.40.41

Phone +27.11.315.5444

Netherlands
Sartorius Stedim Netherlands B.V.
Phone +31.30.60.25.080
filtratie.nederland@sartorius-stedim.com

BrazilSartorius do Brasil Ltda
Avenida Senador Vergueiro 2962
São Bernardo do Campo
CEP 09600-000 - SP- Brasil
Phone +55.11.4362.8900
MexicoSartorius de México, S.A. de C.V.
Libramiento Norte de Tepotzotlan s/n,Colonia Barrio Tlacateco,
Municipio de Tepotzotlan,
Estado de México,
C.P. 54605
Phone +52.55.5562.1102
leadsmex@sartorius.com

Phone +86.21.6878.2300
Sartorius Stedim (Shanghai)
Trading Co., Ltd.
Beijing Branch Office
No. 33 Yu’an Road
Airport Industrial Park Zone B
Shunyi District, Beijing 101300
Phone +86.10.8042.6501
Sartorius Stedim (Shanghai)
Trading Co., Ltd.
Guangzhou Branch Office
Room 1105
Xing Guang Ying Jing Building
No. 119, Shui Yin Road
Yue Xiu District, Guangzhou 510075
Phone +86.20.3836.4193
India
Sartorius Stedim India Pvt. Ltd.
#69/2-69/3, NH 48, Jakkasandra
Nelamangala Tq
562 123 Bangalore, India
Phone +91.80.4350.5250
Japan
Sartorius Stedim Japan K.K.
4th Fl., Daiwa Shinagawa North Bldg.
8-11, Kita-Shinagawa 1-chome
Shinagawa-ku, Tokyo, 140-0001 Japan
Phone +81.3.4331.4300
Malaysia
Sartorius Stedim Malaysia Sdn. Bhd.
Lot L3-E-3B, Enterprise 4Technology Park Malaysia
Bukit Jalil
57000 Kuala Lumpur, Malaysia
Phone +60.3.8996.0622
Singapore
Sartorius Stedim Singapore Pte. Ltd.
10 Science Park Rd
The Alpha #02-13/14
Singapore Science Park II
Singapore 117684
Phone +65.6872.3966
South Korea
Sartorius Korea Biotech Co., Ltd.
8th Floor, Solid Space B/D,
PanGyoYeok-Ro 220, BunDang-Gu
SeongNam-Si, GyeongGi-Do, 463-400
Phone +82.31.622.5700

www.sartorius-stedim.com

Specifications subject to change without notice. Copyright Sartorius Stedim Biotech GmbH. Printed in the EU on paper bleached without chlorine.
Publication No.: S--1526-e191007 · Order No.: 85037-541-65 · Ver. 10 | 2019

Europe