BIOSTAT® RM - Rocking Motion Bioreactors · colour coded plugs and socket for easy operation colour touch screen with Trend & Alarm Display tube and cable organizer ... Advanced

BIOSTAT® RM - Rocking Motion Bioreactors Single-Use Solutions for Screening, Seed & Small Scale Production

Dr. Franziska Faulstich, Product Manager Single-Use Bioreactors, Fermentation Technologies

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Product Family BIOSTAT® RM

From Basic to Advanced

Applications

BIOSTAT® B with RM 20/50

BIOSTAT® B with RM 200

Flexsafe® RM

Ordering

Content

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No gas permeable membranes for

oxygen transfer

Oxygen transfer and mixing are

accomplished by the principle of

wave-induced motion (WIM)

Bubble free overlay aeration

Low shear stress

Wave Induced Motion

Principle: Wave Induced Motion

Sartorius bioreactor product overview – market leader in fermentation

BIOSTAT® B with RM 200 Rocker

Small Scale Benchtop Pilot/Production

BIOSTAT STR® 50 - 2000 L

Univessel ® SU 2 ambr 250 10 – 250 mL

BIOSTAT® RM 20/50 L

BIOSTAT® RM 200

Single Use Upstream Solution

BIOSTAT® B with RM 20/50 Rocker

BIOSTAT® B with RM 200 Rocker

BIOSTAT® RM 20/50 Basic

BIOSTAT® B with

1 L (0.5 L)

200 L (100 L)

100 L (50 L)

50 L (25 L)

20 L (10 L)

10 L (5 L)

2 L (1 L)

RM 20/50 Rocker

Product Family: BIOSTAT® RM

BIOSTAT RM 20/50 - from Basic to Advanced

BIOSTAT® RM 20/50 Basic

• Cell culture without need for sophisticated control

• Cost effective and fast seed production

• Alternative to roller bottle, spinner flask or T-flask

BIOSTAT® RM 20/50 with BIOSTAT® B control tower

• Fully automated and controlled batch, fed-batch

or high cell density perfusion cultures

• Use of Flexsafe® RM bags with single-use pH, DO and biomass sensors

• Highest cell densities/product yields with ease of use

BIOSTAT® RM

BIOSTAT® RM 20/50 basic - Easy to Use Rocker

Working volume 100 ml to 25 L

Rocking rate: 8–42 ± 1 r/min

Rocking angle: 4-10 ± 0,3 °

Perfectly sized, stand alone bioreactor – unique in the market

Based on well proven principle

No internal mixing or sparger device

Cells

• Mammalian cell culture

• Insect cell culture

• Low to medium density microbial cultures

• Shear sensitive cells such as stem cells

BIOSTAT® RM

Load cells – the weighing solution

Weight measurement integrated in Rocker

Monitoring the fill level of bag precisely even during rocking

Space saving

load cell module

BIOSTAT® RM

Rocker integrated load cells for media weight and level control

• Load cells in rocker determine media weight and drive feed pump

• Harvest with manual control (optional GFC)

• Advantages

Consumes less space

Cost efficient, only load cells required

Keeps media in bag constant – very precise measurement with load cells even when rocking

Load Cells

Fully automated and controlled batch or fed-batch processes

High cell density perfusion process using external cell retention unit

Process Options

Cell culture process options of Biostat® RM systems

Which cells can be cultivated with the BIOSTAT® RM systems?

Mammalian, insect and plant cell culture

Low to medium density microbial cultures

Shear sensitive cells such as stem cells

Cell types

BIOSTAT® RM 20/50 Basic Features

optional gassing module with integrated Air/CO2 mixing

individual control of 2 bags (T, gasfl)

• 3 different user levels • service interval display

lid design with space for filter heater

automatic sample function

load cells

colour touch screen with Trend & Alarm Display colour coded plugs and socket for easy operation

tube and cable organizer

standard Ethernet & Modbus RTU interface optional ProfiBus DP interface guaranteed to work with DeltaV

BIOSTAT® RM

filter heater plugged directly in rocker base

Connections for Data Acquisition and Control

ETHERN

ET

third party data acquisition software

driver supplied by customer

I/O protocol supplied by SSB

driver supplied by customer

BioPAT® MFCS

ProfiBusDB

I/O protocol

supplied by SSB

e.g.

BIOSTAT® RM basic

RS232

BIOSTAT® RM

RS232

Modbus RTU

Besides the core functionality of a real SCADA system, BioPAT® MFCS/win offers a number of additional modules for adaptation to individual requirements

SCADA Software

BioPAT® MFCS/win – SCADA Software for Bioprocess Management

• Recipe control according to ISA-88.01

• 21 CFR Part 11 compliance

• Secure integration into company networks

• Flexible device connection facility via OPC

• Replication Manager for automatic batch transfer

• Logging of alarms and transmission to multimedia

devices

• Integrated Design of Experiments (DoE)*

• Integrated Multivariate Data Analysis (MVDA)*

* powered by UMETRICS

BIOSTAT® RM with BIOSTAT® B controller

One control platform for all

Advanced Control System - BIOSTAT® B with BIOSTAT® RM 20/50

Working volume 100 ml to 25 L

Advanced control of gas mixture and flow rate, filling volume and substrate addition

Applications:

• fully automated and controlled batch culture

• fed-batch culture

• high cell density perfusion culture

BIOSTAT® B Controller with RM

Extra small space requirement

in TWIN configuration

BIOSTAT® B with Rocker

• Basic and advanced solutions

• 4 independent gassing lines

with 4 mass flow controllers

• Perfusion option via connection to external cell retention device, e.g. ATF

(100l & 200l bags with perfusion membrane no longer available)

• Up to 3 media feeds

• Up to 2 gravimetric flow controllers

BIOSTAT® B with Rocker

The BIOSTAT® B – From June 2014 on with RM Rocker

• BIOSTAT® B with RM Rocker is the successor of BIOSTAT® RM Optical and Perfusion

BIOSTAT® B Controller with RM

BIOSTAT® B The Gold Standard of benchtop bioreactors

WM 114 Easy load pumps

12” touch screen with flush housing integration for liquid

protection

Largest installation base worldwide with reference applications for many processes

Controller, software & culture vessels made in-house

Available in single and twin

configurations

Connection to glass and single-use vessels and

Rocker

Various gassing and feeding strategies

available

BIOSTAT® B

UniVessel® UniVessel® SU

Rocker 20/50 Rocker 200

BIOSTAT® B

One control platform for all*

* depending on tower configuration

Storage Dish for accessories

12” touch screen with frameless design for liquid protection

Lifting Handles for easy transportation

BIOSTAT® B

WM 114 Easy load pumps Sensor Field located at the front

BIOSTAT® B

New gassing module old BIOSTAT® RM optical vs. BIOSTAT® RM with BIOSTAT® B

Mixture of

• exclusive flow (air, N2, O2)

• Additive flow (CO2)

• with 2 mass flow controllers

4 independent gassing lines


• either with DO cascade control or optional advanced DO controller

BIOSTAT® RM with Controller

26 May 2014

New options for media feeds old BIOSTAT® RM optical vs. BIOSTAT® RM with BIOSTAT® B

• No CTO media feed or GFC

• No CTO rocker weight measurement

• No CTO level control



• Load cells integrated in Rocker for media weight and level control


New solution for perfusion old BIOSTAT® RM optical vs. BIOSTAT® RM with BIOSTAT® B

One balance to weigh the feed

One balance to weigh the harvest

No direct measurement of cell culture volume

Load cells in rocker determine media weight and drive feed pump

Harvest with manual control (optional GFC)

Precise solution, but some disadvantages : • Space requirement • Price • Does not detect media loss due to

evaporation

Advantages : • Consumes less space • Cost efficient, only load cells required • Keeps media in bag constant • Very precise measurement with load cells even

when rocking


Features, Advantages & Benefits part 1 Feature Advantage Benefit

Rocking Motion Technology Gentle and efficient mixing. Well established wave-type technology Longest history in single use bioreactors.

Well known to customers and FDA, large number of references.

Highly flexible bag design

Different sizes from 0.1 L to 100 L working volumes, many different connections, with or w/o pH, DO & biomass sensors.

Allows highest flexibility of processes with low consumable costs.

Single use sensors

pH, DO and biomass sensors integrated in the bag, delivered sterilized and pre-calibrated.

Eliminate risk of contamination, reduce calibration effort.

Over Pressure Prevention System Controller measures bag pressure and keeps it below 30 mbar.

Highest possible safety against overpressure. Risk of bag damage by overpressure is eliminated.

Integrated Air/CO2 module for basic rocker (option)

Allows to work with fixed percentage of CO2 (“incubator style”).

Turns rocker into fully functional stand alone unit for simple cultivations.

.

Features, Advantages & Benefits part 2

Feature Advantage Benefit

BIOSTAT® B controller Newest generation of bioreactor control system with full feedback control of all relevant process parameters.

Well known to the industry, easy to use, same controller for many different SSB instruments.

Heating and Cooling option Heating cooling by stainless steel coil on bag holder and thermostat unit in control tower.

Precise temperature control even in high ambient temperatures and lower cultivation temperatures. Possibility to run multiphasic processes.

Touch screen user interface Graphical display for operation and data display.

Easy to use, helps to avoid errors.

Individual control (T, gassing) of two bags on one rocker

Great flexibility: allows different process conditions simultaneously.

Save time and space.

Improved filter heater Better heating efficiency, connects directly into rocker. Monitoring connection of filter heater before start of process.

Even more efficient prevention of filter blockage. Alarm if user forget to plug in heater. Improved process safety.

.

Features, Advantages & Benefits part 3

Feature Advantage Benefit

Modbus RTU and Ethernet port (standard) and Profibus DP (optional)

Allows direct connection to third party software (e.g. historian). I/O protocol supplied by SSB.

Enables integration into facility networks.

New lid design and cable/tube organizer

Space for filter heaters, lid is click-fixed to bag holder. Cables and tubes are neatly organized.

Prevents bending of exhaust tubes, enhances process safety. Prevents “tube spaghetti”.

Color coded plugs and sockets Connection made easy. Enhanced ease of operation.

Electronic angle setting Angle can be set in Rocker display and Tower.

Include angle in automation strategy.

Improved communication between rocker and Tower

Process values, set points, alarms, controller parameters are transferred in both ways.

Enhanced flexibility, enhanced process safety.

Same well-known BIOSTAT® B control tower

Configurability of pumps and MFCs

Available in single & twin configuration

Improved hood design with space for filter heaters

Integrated weight measurement with load cells (optional)

Material of entire system (incl. lab-cart) optimized for use in clean rooms

Highlights

Advanced Control System - BIOSTAT® B with RM Rocker

SSB vs. Competition – Key Differentiators / USPs

BIOSTAT B - Twin setup • we are the only manufacturer who can control two rockers with one control tower • saves space • RM 20/50 only, RM200 – twin BAG configuration

RM 200 • Modular concept allows space saving arrangement • Same well-known Biostat® B control tower as for Biostat RM 20/50 - no special training needed, user

friendly • Configurability of pumps and MFC

Flexsafe Film • Industry leading, proprietary S80 film • Ultimate assurance of supply (Excellent cell growth proven by independent Dechema study)

BioPat® ViaMass • single-use viable biomass sensor • Only single-use wave style bags in market with non-invasive viable biomass measurement

USPs

BIOSTAT® B with RM 200

Next Generation of Rocking Motion Single-Use Bioreactor

Applications of BIOSTAT® RM 200 system

Preclinical and clinical studies - fast protein and cell supply

Large scale seed expansion for large bioreactors, e.g. stirred tank bioreactor

Small scale production of monoclonal antibodies, recombinant proteins and vaccines

cGMP production

BIOSTAT® RM 200

Seed process RM 20 RM 200 STR 2000

BIOSTAT B with RM 200 Rocker

OLD

2007 2015

NEW

• modular design for flexible arrangement

• integrated load cells

• twin bag option

load cells

Old vs. New RM 200

New gassing module

Mixture of

• exclusive flow (air, N2, O2) and

• additive flow (CO2)


4 independent gassing lines


• either with DO cascade control or optional

advanced DO controller

Old vs. new RM 200

New options available

• Perfusion option via internal membrane for fully automated continuous processes

• No CTO media feed or gravimetric flow controller option

• No CTO rocker weight measurement option

• No CTO level control option

• Perfusion option via connection to an external cell retention device, e.g. ATF

(100l & 200l bags with perfusion membrane no longer available)



• Rocker integrated load cells for media weight and level control

Old vs. new RM 200

Description of the BIOSTAT® RM 200 system

The system consists of :

BIOSTAT® B control tower

BIOSTAT® RM 200 Rocker

Flexsafe® RM 100 L or 200 L bag(s)

with single use pH & DO sensors

Lab-cart

Working volume from 10 L up to 100 L

Single Bag or Twin Bag Configuration

No basic version of RM 200

Twin Bag Configuration

Single Bag Configuration

Biostat® RM 200

NEW Corporate design

as for BIOSTAT® RM 20/50

Integrated load cells (optional)

Flexible arrangement

Efficient and gentle mixing

No high voltage connection required

CE-marking, UL/CSA (EN61010-1)

Heating or heating/cooling function

(optional)

BIOSTAT® RM 200 - Rocker

BIOSTAT® RM 200 Rocker – the new generation

Rocker: integrated weight measurement

Precisely monitor fill level of bag even during rocking

Space saving

Optional

load cells

New Features

Load cells – the weighing solution

Twin Bag version of the device with two culture bags

different temperatures can be set for the two heating elements

Large opening for sampling

Cable/Tube organizer New hood design with space for filter heater

New Features

Proven DCU controller and software

Control of glass and single-use vessels and Rockers

WM 114 fast load pumps

Various gassing and feeding strategies

Available in single and twin bag configuration

Overpressure control

Feedback control of temperature, pH, DO and agitation (rocker speed & angle)

Connectable to advanced SCADA software, BioPAT® MFCS 4 or BioPAT® MFCS/Win incl. OPC module

BIOSTAT® B

BIOSTAT® B control tower – the gold standard

• Robust platform for controller

• 3 shelves - middle one is adjustable

• incl. 2 baskets for bottles and cable/tube organizer

• Flexible use – for external pumps, feeding bags

• Easy to clean – developed for clean room use

• Made of stainless steel

Lab-Cart

Flexible arrangement with the lab-cart

third

par

ty d

ata

acqu

isiti

on s

oftw

are

I/O protocol

supplied by SSB

BioPAT® MFCS 4 or BioPAT® MFCS/win

BioPAT® MFCS/win incl. OPC module

OPC

third

par

ty d

ata

acqu

isiti

on s

oftw

are

OPC

BioPAT® DCU OPC Server.Net

ETHERNET

BIOSTAT® RM 200

Communication

Communication and Data Acquisition

Flexsafe® RM – Disposable Cultivation Bag

Excellent Cell Growth

Robustness

Consistent Quality

S80 FILM Multilayer film structure

The new benchmark PE film represents

optimal combination of cell culture

performance and physico-chemical

properties

Flexsafe® meets the most stringent

customer needs for safer bioprocessing

Flexsafe® RM bags

Flexsafe® RM – bioprocessing bags of Flexsafe® Bag Family

Sartorius_robustness170114.mp4

BAG DESIGN

Basic bags

Optical bags with single-use pH, DO and viable biomass sensors

Perfusion bags

TUBING MATERIAL C-Flex® 374 – all tubes weldable Silicone PharMed® Natvar ABL-1222 TPE

BAG SIZES Total volume: 1 L, 2 L, 10 L, 20 L, 50 L,

100 L, 200 L Working volume: 50% of total

volume

PORTS Harvesting Sampling Probes Addition Surface aeration

Flexsafe® RM bags

June 2016 Page 6

Main Competitors – Film Overview Product SSB Flexsafe RM GE Cellbag Meissner FlexGro

Film Flexsafe Bioclear 11 TepoFlex

Working Volume Up to 100L Up to 100L Up to 25L

Online Biomass Measurement Yes No No

Raw material supplier agreements: change notification agreement with film

supplier 10-year contract with film

manufacturer Safety stocks of resin & films for up to 2

years supply Multiple bag mfg & sterillization sites

Yes Yes Yes Yes

Yes No No ?

No No No No

Specifications for resins and additives

– Access to formulation – Control of resin

formulation – Access to polymer and

additives by CAS number

commercially available LLDPE resins

Guarantee forward and backward traceability of every component in biocontainer assembly

Full Control of Extrusion Process Yes No No

Cell Growth Data Tested with 9 different cell lines

1 cell line (CHO DG44) No

EtOH extraction Pure EtOH 112 days, 40 °C

20% EtOH 28 days at 50°C

96% EtOH 90 days, 40°C

How to order the BIOSTAT® RM system?

Quotations are available via your local application specialist and sales representative.

Each quote is generated via our Product Configurator software program for fast turn-around, Sartorius will help you identifying your requirements.

Ordering information

Ordering information

How to order Flexsafe® RM bags?

Article Number Product Description Flexsafe® RM qty per order code

min. order quantity

min. order quantity Article Number Product Description Flexsafe® RM qty per order

code min. order quantity

min. order quantity

Flexsafe® RM Basic bags per box bags box Flexsafe® RM Perfusion bags per box bags box

DFB001L Flexsafe® RM 1L basic (5 pcs) 5 10 2 DFP002L--SM Flexsafe® RM 2L perfusion pro 1,2 µm (3 pcs) 3 3 1

DFB002L Flexsafe® RM 2L basic (5 pcs) 5 5 1 DFP010L--SM Flexsafe® RM 10L perfusion pro 1,2 µm (3 pcs)

3 3 1

DFB002L----01SC Flexsafe® RM 2L basic SC (5 pcs) 5 10 2 DFP020L--SM Flexsafe® RM 20L perfusion pro 1,2 µm (3 pcs)

3 3 1

DFB010L Flexsafe® RM 10L basic (5 pcs) 5 5 1 DFP050L--SM Flexsafe® RM 50L perfusion pro 1,2 µm (3 pcs)

3 3 1

DFB010L----01SC Flexsafe® RM 10L basic SC (5 pcs) 5 10 2 DFP002L--AT Flexsafe® RM 2L perfusion ATF (3 pcs) 3 3 1

DFB020L Flexsafe® RM 20L basic (5 pcs) 5 5 1 DFP010L--AT Flexsafe® RM 10L perfusion ATF (3 pcs) 3 3 1

DFB020L----01SC Flexsafe® RM 20L basic SC (5 pcs) 5 10 2 DFP020L--AT Flexsafe® RM 20L perfusion ATF (3 pcs) 3 3 1

DFB050L Flexsafe® RM 50L basic (5 pcs) 5 5 1 DFP050L--AT Flexsafe® RM 50L perfusion ATF (3 pcs) 3 3 1

DFB050L----01SC Flexsafe® RM 50L basic screw cap (5 pcs) 5 10 2 DFP100L--AT Flexsafe® RM 100L perfusion ATF (2 pcs) 2 4 2

DFB050L----01US Flexsafe® RM 50L basic GE rocker (5 pcs) 5 5 1 DFP200L--AT Flexsafe® RM 200L perfusion ATF (2 pcs) 2 4 2

DFB100L Flexsafe® RM 100L basic (2 pcs) 2 4 2 Flexsafe® RM ViaMass

DFB200L Flexsafe® RM 200L basic (2 pcs) 2 4 2 DFB010L----VM Flexsafe® RM 10L basic Viamass (5 pcs) 5 5 1

Flexsafe® RM Optical DFB020L----VM Flexsafe® RM 20L basic Viamass (5 pcs) 5 5 1

DFO002L Flexsafe® RM 2L optical (5 pcs) 5 5 1 DFB050L----VM Flexsafe RM 50L basic Viamass (5 pcs) 5 5 1

DFO002L----01SC Flexsafe® RM 2L optical SC (5 pcs) 5 10 2 DFO010L----VM Flexsafe® RM 10L optical Viamass (5 pcs) 5 5 1

DFO010L Flexsafe® RM 10L optical (5 pcs) 5 5 1 DFO020L----VM Flexsafe® RM 20L optical Viamass (5 pcs) 5 5 1

DFO010L----01SC Flexsafe® RM 10L optical SC (5 pcs) 5 10 2 DFO050L----VM Flexsafe® RM 50L optical Viamass (5 pcs) 5 5 1

DFO020L Flexsafe® RM 20L optical (5 pcs) 5 5 1 DFO100L----VM Flexsafe® RM 100L opt ViaMass (2 pcs) 2 4 2

DFO020L----01SC Flexsafe® RM 20L optical SC (5 pcs) 5 10 2 DFO200L----VM Flexsafe® RM 200L opt ViaMass (2 pcs) 2 4 2

DFO050L Flexsafe® RM 50L optical (5 pcs) 5 5 1 DFP010L--SMVM Flexsafe® RM 10L perfusion Viamass (3 pcs) 3 3 1

DFO050L----01SC Flexsafe® RM 50L optical SC (5 pcs) 5 10 2 DFP020L--SMVM Flexsafe® RM 20L perfusion Viamass (3 pcs) 3 3 1

DFO100L Flexsafe® RM 100L optical (2 pcs) 2 4 2 DFP050L--SMVM Flexsafe® RM 50L perfusion Viamass (3 pcs) 3 3 1

DFO200L Flexsafe® RM 200L optical (2 pcs) 2 4 2 DFP010L--ATVM Flexsafe® RM 10L ATF Viamass (3 pcs) 3 3 1

Customized design DFP020L--ATVM Flexsafe® RM 20L ATF Viamass (3 pcs) 3 3 1 DFCnnn (customer specific)

Flexsafe® RM customized 10 DFP050L--ATVM Flexsafe® RM 50L ATF Viamass (3 pcs) 3 3 1

DFP100L--ATVM Flexsafe® RM 100L ATF ViaMass (2 pcs) 2 4 2

DFP200L--ATVM Flexsafe® RM 200L ATF ViaMass (2 pcs) 2 4 2

22 June 2016 Page 2

BioPAT ® ViaMass – single-use biomass sensor

• for non-invasive measurement of viable biomass

Art. No Description

DFB010L----VM Flexsafe® RM 10L basic ViaMass (5 pcs)



DFO010L----VM Flexsafe® RM 10L optical ViaMass (5 pcs)





DFP010L--SMVM Flexsafe® RM 10L perf ViaMass (3 pcs)



DFP010L--ATVM Flexsafe® RM 10L ATF ViaMass (3 pcs)





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Installation

FAT & SAT

IQ | OQ support & documentation

Calibration services

Spare part sales

Preventive maintenance contracts

Customer-specific maintenance contracts

Instrument repairs

Technical & application support

Practical & technical operator training

Additional Information

Our Services

Page 48

Thank you very much for your attention!

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Documents

BIOSTAT® RM - Rocking Motion Bioreactors · colour coded plugs and socket for easy operation colour touch screen with Trend & Alarm Display tube and cable organizer ... Advanced