BPD SUT Capabilities - Thermo Fisher...
Transcript of BPD SUT Capabilities - Thermo Fisher...
2
Premier Brands
• 50,000 employees in 50 countries
• $17 billion in annual revenues
• Unparalleled commercial reach
Unmatched Depth
• Leading innovative technologies
• Applications expertise
• Lab productivity partner
Global Scale
We Are The World Leader in Serving Science
3
Analytical Instruments Life Science Solutions
Laboratory Products
and Services
Specialty Diagnostics
GlobalFiler
PCR Amplification Kit
25%
19%
19%
37%
$17B Revenue
Mass
Spectrometry
Q-Exactive HF
mass spectrometer
Chromatography
Vanquish
Ultra HPLC
Chemical and
Environmental Analysis
Gemini handheld
analyzer
Clinical
Diagnostics
Oral-Eze Oral Fluid Collection System
Transplant
Diagnostics
NXType High
Resolution Genotyping
ImmunoDiagnostics
ImmunoCAP Allergy
and Asthma Tests
Microbiology
Antimicrobial Susceptibility Testing Solutions
QuantStudio
Dx R qPCR
Genetic
Sciences
Human
Identification
Sorvall WX+
Ultracentrifuge
Lab Equipment
Lab
Consumables
E1 ClipTip
Pipette
system
Distribution and
BioPharma
Services
Chemicals
Clinical Oncology
Next Gen Sequencing
Our Business Segments
Enterprise and
Instrument
Services
Biosciences
Life Science
Reagents
Pathology
Rotary Microtome
BioProduction
Single-use
Systems
5
Productivity
Improving
Maintaining cGMP
Compliance
Risk
Mitigation of
Supply Chain
Transparency
Discovery
Accelerating
Costs
Reduction of
BioPharma
Industry
A Growing and Changing Biotherapeutics Market
Right the First Time. Every Time.
Quality Continuity of
Supply
BioPharma Industry Challenges
6
Freedom™ CHO
cell lines
Analytical services
Media optimization
services
Gibco™ Media
Express™
BioProcess
Containers (BPC)
Single-use mixers,
bioreactors and
fermentors
Transfer assemblies
Inflation and integrity
test system
BioProcess
Containers (BPC)
Harvest and
separation products
Single-use heat
exchanger
Single-use aseptic
sampling system
BioProcess
Containers (BPC)
Single-use mixing
systems
Transfer assemblies
BPCs, manifolds,
containers
Storage and
transport
Single-use filling
system
Frozen Handling
system
Bulk Storage & Final Fill
DOWNSTREAM
Cell Line Development & Media Optimization
QC & Analytics
Mixing, Cell Culture & Fermentation
Harvest & Collection
Purification
UPSTREAM
Microbial identification and Glycan analytics
Sample prep and automation Mycoplasma and viral detection
Analytical columns
Best-in-class solutions for up- and downstream bioprocessing
7
Drive Your Supply Chain Confidence
To have your
supplies when
you need them
Business Continuity
Key initiatives…
• Redundancy of manufacturing for key cell culture and single-use products
• Plans for effective prevention and recovery from operational disruption
• All sites Environmental, Health & Safety (EHS) compliant
Safety Stock
• Maintenance of intermediate and finished good safety stocks
• Product can be shipped from our warehouses within 2 days of your request for single-use
• Approximately 5 million liters of finished goods stored each month for cell culture
Demand Planning
• Help eliminate lead times by aligning Thermo Fisher’s production schedule to yours
• Some products can be available 4 weeks prior to your target date
Assurance of Supply
8
Auckland and Christchurch,
New Zealand Newcastle, Australia
• Sera
• Protein products
• GMP 21 CFR 820
Cramlington, UK
• Bioprocess containers
• Class 10,000/ISO 7
clean room
Bedford, MA
• Chromatography resins
• ISO 13485
Logan, Utah
• Bioprocess containers
• Single-use technologies
• Class 10,000/ISO 7
clean room
Grand Island, NY
• Cell culture media, reagents
• Sera
• ISO 13485
• GMP 21 CFR 820
Paisley, Scotland
• Cell culture media, reagents
• ISO 13485
• GMP 21 CFR 820
Matamoros, Mexico
• BioProcess
Containers
• ISO 13485
• FDA Registered
Millersburg, PA
• BioProcess Containers
Single-use technologies
• ISO 13485
• FDA Registered
Naarden, The Netherlands
• ISO9001 certified
• Affinity ligands
Warrington, UK
• Analytics kits
Global BioProduction Manufacturing Facilities
Indicates a SUT facility
9
The Power of ONE Brand
Company
Name
Premier
Product
Brand
Product
Line
Identifiers
Product
Names
HyPerforma (for legacy Thermo
Fisher hardware)
• Single-Use Mixers
• DS 300
• Single-Use Bioreactors
• Single-Use Fermentors
• Drums
imPULSE, DHX,
Acclimate, inSITE, Precise (for former ASI hardware)
• Single-Use Mixers
• Heat Exchanger
• Frozen Handling System
• Integrity Testing System
• Single-Use Filling System
Aegis5-14, CX 5-14,
ASI 26/77, ASI 28 (for film platforms)
• Labtainer
• Productainer
• Powdertainer
• Harvestainer
• Rock-It
• Transfer
Assemblies
• Manifolds
• Services
10
The Power of the Thermo Scientific Brand
Portfolio Options
& Diversity
Assurance
of Supply
Improved
Productivity Innovation
A complete portfolio of best-in-class
hardware including mixers,
fermentors, bioreactors, heat
exchangers, point-of-use integrity
testers and filling systems.
Expansive film and BioProcess
Container (BPC) options to deliver
optimal film and configurations
based on performance, chemical
and biological properties
Opportunity to partner as
qualified primary and secondary
supplier through separate legal
entities with global
manufacturing facilities
Provide manufacturing
redundancy in each of its
bioprocess facilities for all films
A continuous pipeline of
innovative solutions and
capabilities across our wide
range of products and
applications.
Continued investments to
sustain our best-in-class
products with customers’
evolving requirements.
More choices add more
flexibility to customer’s
manufacturing capabilities
Meet customer demand for
both quality and productivity
in bioprocessing
Benefits to our single-use customers
12
Films
Film material: CX5-14, Aegis 5-14, ASI 26/77, ASI 28
Sizes: 50 mL to 5,000 L
Surface Area/Volume ratio: Small bags -High SA/V, Large Bags - Low SA/V
Fluid compositions: Media, Buffers, Excipients, Intermediates, Drug products
Fluid Residency Times: Short term to Long term
Temperatures: -80˚C to +60˚C
13
Our BioProcess Containers are specifically designed for single-use bioprocessing and
meet stringent quality standards. Due to the film strength, robustness and flexibility, our
BPC are suitable for use in upstream, for cell culture and fermentation, or downstream,
for sophisticated applications or simply as holding and transfer systems in cGMP
bioprocessing facilities.
Benefits:
• Outstanding physical characteristics for superior puncture
resistance and content integrity
• Coextruded structure to minimize delamination potential
• Greater cleanliness and low leachable/ extractable profiles
• Non–animal origin formulations for safer contact surfaces
• High gas- and liquid-barrier properties for better content stability
• Validation packages assurance of product performance
• Sizes ranging from 50mL – 5,000L
Film Excellence - The Reason why Customers Choose Us
14
BPC – Standard and Custom Designs
Chambers
•2 D
•3 D
•Manifolds
Specialty
•Powdertainer
•Harvestainer
Storage and Transport
•Drums
•Bins
•Docking Systems
Integrated
•S.U.M.
•S.U.B.
•S.U.F.
•DHX
•Smartainer
Applications
•Media hydration
•Cell Culture
•Harvest
•Freeze / Thaw
•Buffer Prep
Open architecture approach for component customization
15
• Manufacturing >1.5 million BPC
chambers annually
• Standard and custom configurations in
as little as 4 weeks
• Powder and liquid handling, incl. liquid
shipping
• Largest standard component library to
• Shorten lead times
• Provide choice and flexibility
• Support highest quality standards
• Multiple manufacturing sites on two
continents
• 97% on-time and in full product delivery
• Quality documentation and validation
guides available
Leading Supplier of 2D & 3D BPC
>20 years developing SUT products specifically for the biopharma industry
Labtainer 50 mL-50 L
BioProcess
Containers 50-3000 L
Complex Manifolds 50-3000 L
16
• Standard and custom configurations for
upstream and downstream applications
• Open architecture approach (filters,
sensors, connectors etc.)
• Single-film qualification from
30 L – 5000 L for hardware BPC
• Multiple manufacturing sites on two
continents
• Zero lead time and stocking products
available to guarantee assurance of
supply
• Optional Point-of-Use Integrity Testing
System for any BPC available
• Multiple film options for single-use
hardware systems
Most Widely Used 3D BPC for SUT in the Industry
>20 years developing SUT products specifically for the biopharma industry
Single-Use Bioreactors
& Fermentors 30-2000 L
Single-Use Mixers 50-5000 L
17
Your Partner in Single-use Fluid Transfer Assemblies
Your complete end-to-end solution provider
Your trusted guide for single-use technology and applications
• Fastest industry lead times*
• A single point of coordination for
design, manufacturing and service
• Helps reduce your burden of
required equipment and upkeep
• Helps free your personnel for
other crucial activities
• Fluid transfer assemblies are customized
to your existing processes
• Designs accommodate a variety of
components using our open architecture
approach and draw from our qualified
standard components library, the
industry’s largest
• Delivering the benefits of single-use
technology**
3 week lead times for sterilized products
19
Single-use Bioreactor BPC
Open pipe sparger Frit sparger
Pressure sensor
Port labeling on bags and cables
Probe belt for classical
& single-use sensors
Optional sample
manifold
Single-use connectors
Drill hole sparger Open pipe sparger
20
Two S.U.B. Family Offerings
Open Architecture Thermo Scientific™ S.U.B.
Integrate with the control platform
of your choice
Turnkey Solutions Thermo Scientific™
HyPerforma™ S.U.B. TK
State-of-the-art S.U.B. with integrated
control choices from two suppliers
Choice of leading controller platforms for Turnkey S.U.B.
Scalability from 25 to 2000L
21
Single-use Process Analytical Technologies (PAT)
Pressure
Technologies emerging:
CO2
pH
DO
Cell Mass
Metabolites
Technologies available today:
Cutting-edge Technologies
22
Single-use Mixing Technologies
• Thermo Scientific HyPerforma Single-use Mixers (S.U.M.s)
• Thermo Scientific imPULSE Single-use Mixers (S.U.M.s)
23
imPULSE Core imPULSE Elite imPULSE MDS SUM DS 300 Mixtainer
Description Mixer-Simple Control Mixer-High Control Mixer-Dock-Ship Mixer-Simple
Control Mixer-Dock Mixer-Dock-Ship
Size Range (L) 30 – 10,000L 30 – 10,000L 30, 50 50 – 2,000L 50 – 300 L 50, 100, 200
Linear Scalability Yes Yes Yes Yes Yes Yes
Tank Temperature Control No Jacket Heat No Jacket Heat No No
Bag Auto Inflation and Automatic Vent Control No Yes No No No No
Sensors No
pH, DO, CO2, Temp,
Weight, Conductivity, Fluid
Height
No pH, DO, Temp,
Weight, Pressure No No
Base Mobility Fixed/Casters Fixed/Casters Fixed/Casters Fixed/Casters Casters Casters
Mixing Technology Btm-imPULSE Btm-imPULSE Btm-imPULSE Top Stir Tank Top Stir Tank Btm-Stir Bar
Controls Self sustained e-box e-box e-box, PLC, PC,
Delta V e-box Handheld controls Power, Speed
Minimum Mixing Volume 1% 1% 1% 20% 20% 1%
Drain Location Btm Btm Btm Btm Btm* Btm
Particulate Generation None None None None None Med
FAT/SAT/Service/PM/Validation Support Yes Yes Yes Yes Yes Yes
Fluid Vortex No No No No No No
Tank Materials SST SST SST, Plastic SST Plastic Plastic
Sparge Capable No Yes No Yes No No
Available Mixing Platforms
* - Bottom drain for 50L/100L/200L Drums only and open top drain for 300L Drum
24
Single-Use Mixer (S.U.M.):
• 50 L
• 100 L
• 200 L
• 500 L
• 1000 L
• 2000 L
HyPerforma Mixing Solutions
Mixing solutions designed to meet your needs
HyPerforma S.U.M. Animation Video Link
DS 300:
• 50 L
• 100 L
• 200 L
• 300 L
Mixtainer:
• 50 L
• 100 L
• 200 L
25
imPULSE Core:
• Superior mixing with basic
controls and monitors
• 30 L
• 50 L
• 100 L
• 250 L
• 500 L
imPULSE Mixing Solutions
imPULSE Elite:
• Flexible platform that is
customized to your process
• 30 L
• 50 L
• 100 L
• 250 L
• 500 L
imPULSE MDS:
• Superior mixing,
modularity with a safe and
secure shipping container
• 30 L
• 50 L
imPULSE Animation Video Link
• 1,000 L
• 2,000 L
• 3,000 L
• 5,000 L
• 10,000 L
• 1,000 L
• 2,000 L
• 3,000 L
• 5,000 L
• 10,000 L
27
Expanding “Normal” Platform Capabilities
Microbial Production Platforms
• Small, non-glycosylated proteins
• Perceived as low cost
Status Quo
• Each process developed/qualified de-novo
• Carries high risk of failure
• OK 25 years ago… now?
Current Single-use Optimized for
Shear-Sensitive Cell culture
• Low power input, mixing
• Limited oxygen transfer rate (OTR)
• Exhaust management
Modified SUB’s don’t deliver for
demanding fermentation processes
28
30 L and 300 L S.U.F.
First Large Scale Single-use Fermentation Solution
Key Features
The S.U.F. is a fully functional fermentor vessel including
single-use sterile contact surfaces for mixing, venting, sparging and
temperature sensing. Additional ports are included to allow choice of
aseptic connections for filling, emptying and sampling.
• Unique proprietary mixing system enables conventional overhead mixing while
maintaining sterility and integrity of the S.U.F. BPC.
• Minimized vessel footprint and reduced hold-up volumes.
• Simplified bag loading with a front access door.
• Side and bottom jacket for effective heat transfer.
• Cable management system offers greater organization
for electrical cables, tubing and line sets while making
the unit easier to clean.
• Dedicated adjustable tool holder keeps necessary tools.
• State-of-the-art foam sensor that helps prevent exhaust
filter failure.
Modified SUB’s don’t deliver for demanding
fermentation processes
29
Agitation: Drive Train
3 Rushton Impellers
• Industry standard for rigorous mixing
• Multiple impellers increase mixing distribution
• Generates mixing shear and bubble breakup
4 Baffles
• Breaks up vortex of center driven mixer
• Converts some radial mixing to vertical
Powerful Mixing
• 100x the nominal power of traditional S.U.Bs
• 2.27W/L (11hP/1000gal)
Low Volume Mixing
• 5:1 turn down ratio (supports full RPM range)
• 30L S.U.F. (6L min), 300L S.U.F. (60L min)
Volume flexible, high power, uniform mixing
31
HyPerforma Smartainer Systems – Stainless Steel
Key Advantages
• Thermo Scientific™ HyPerforma™ Smartainer™ systems have
chambers constructed of Thermo Scientific Aegis5-14 Film and
CX5-14 Film with dimensions optimized for Smartainer systems.
• Smartainer systems are simple, durable and economic containers
constructed in 304 stainless steel.
• They are intended for in-house handling applications in critical areas.
• Smartainer systems are non-jacketed outer container systems
available in unit volumes of 200, 500, 1,000, 1,500 and 2,000L.
• It is a modular system with optional accessories for mobility and BPC
handling.
• Jacketed versions available in all sizes on a custom basis, for
applications where heating or cooling are required.
• Smartainer systems are designed to allow both top and bottom
discharge from BPCs.
• Standard BPC configurations are available in unit volumes of 100,
200, 500, 1,000 and 1,500L.
• Wide configuration available for 1,000 L – 1,500 L using only the
ASI 26/77 film
32
Key Advantages
• Standard sizes (100 L – 1,000 L)
• Ease of use and operation
• Clean room grade swivel casters and wide
configurations (available up to 1,000 L)
• Smooth, clean room grade plastic
Accent Outer Support Containers - Plastic
Choose from a comprehensive line of economical, standard or fully customizable
containers to best fit a variety of applications. There are also standard 3D BPCs
for each size, material and configuration with standard port configurations.
33
DHX Heat Exchanger
• A modular heat exchanger that employs a plate and frame concept,
using a single-use BPC as the sterile fluid path.
34
DHX Heat Exchanger
Features and Benefits
• Single-use, sterile fluid path
• Completely isolated flow paths for process and heat
transfer fluid
• Small and modular footprint
• Easy to integrate in new or existing processes
• Dimpled jacketing on plates provide turbulent flow
• BPCs fill in place with little operator interaction
• Reduced infrastructure requirements
• Reduced processing time
• Adaptable to your unique process
DHX Overview Video Link
35
DHX Heat Exchanger
Single-use BPC Assembly
• Single-Use BPC Material of construction:
low density polyethylene (ASI 26/77 film)
• Interconnecting tubing: C-Flex
• Pressure/temperature rating (Installed in
DHX plate system): 20 PSIG at 122˚F (50˚C)
• Open architecture connections and assemblies
• Flow rate capacity: Up to 15 Liters per Minute (LPM)
36
inSITE Integrity Testing System
• inSITE is the only true point-of-use integrity testing system that allows users to confirm the
integrity of single-use bags inside the tank that is about to be filled.
37
inSITE Integrity Testing System
Advantages
Using sterile air, the system inflates bags to a precise
pressure within the container and monitors for pressure
decay that would indicate a leak. Both gross and fine flaws
can be detected in any type of bag.
• Multichannel, point-of-use integrity testing
• Gross and fine leak detection
• Guided validation setup
• Tests BPCs up to 5,000 L
• Inflation procedure improves loading and
placement in tanks
• Liquid filling cycle regulates internal
pressure while fluid is being introduced
inSITE Overview Video Link
38
Acclimate Frozen Handling System
• The Acclimate system is a single-use Bioprocess Container (BPC) and shell combination
used for freezing and thawing bio-pharmaceutical fluids in commercial equipment such as
walk-in freezers, cold rooms, temperature controlled cabinets or water baths.
39
Acclimate Frozen Handling System
Features and Benefits
• Integral BPC and shell in sizes:
2, 6, 12 or 16 Liters
• Easily fits and Stacks in Commercial Freezing
Equipment
• Optional Sample BPC
• Capable of Withstanding Temperatures as low
as -80˚C and thaw conditions to ambient room
temperature and maintaining integrity.
• Pre-assembled
• Compact and Durable Design
• Single-Use
• Pre-sterilized and ready to use
Uniform Fluid Distribution Design
• The acclimate BPCs are designed with patent-pending
tuft(s) which help distribute the fluid during filling then
holds the fluid in a uniform manner as it expands
during freezing
40
Three60 Single-use Sampling System
• The simple design behind the three60 sampling system allows you to take a representative
sample of your product with minimal effort.
41
Three60 Single-use Sampling System
Kit to Tank
The Three60 is pre-irradiated and assembled into a
one-piece kit. Simply remove the pre-sterilized device from the
kit and apply to the vessel.
• 1: Quick Turn three60 Valve
The face of the three60 valve can be sterilized with the tank through
traditional CIP / SIP processes. The valve has four sterile assemblies.
This keeps the product and technician contaminate free.
• 2: Pinch and Cut Sterile Disconnections
The Pinch and Cut Disconnections allow you to quickly separate the sample
and eliminates the need for tools or tube sealing.
• 3: Injection Ports
Luer lock injection site. Extract through either the septum or twist-off
luer to pour.
• 4: Pre-Irradiated Bag Sets
ASI provides pre-irradiated bag sets in sizes ranging from 50 ml to 2 Liters.
1
2
3
4
Three60 Animation Video Link
42
Precise Single-Use Filling System
• A small, modular machine that employs disposable tubing assemblies and BPCs to create a
clean and efficient method of filling BPCs.
43
Types of Precise filling systems
Manual Semi-Automatic Semi-Automatic with Integrated Weight Scale
Advantages Manual Operation
Utilizes off-the-shelf
peristaltic Pump for
volumetric metering
Semi-automated
operation
Utilizes off-the-shelf
peristaltic pump for
volumetric metering
Foot Pedal
Operation
Fill Accuracy +/- 2 ml
Programmable Weighing Terminal for
product ID storage
Per batch calibration is NOT required
Variable Fast Feed/Slow feed selection
Several programming features including
Auto learn (if required)
Challenges Manual Operation
Fill Accuracy ≥ 2%
Must be calibrated
per batch
Fill Accuracy ≥ 2%
Must be calibrated
per batch
Depending on size of BPC and precise
accuracy of the fill, fill times may be slower
44
• The Precise Filling Connector is an integral part
of the pre-irradiated BPC.
• Simply place the BPC and connector assembly
into the cradle and operate the handle or foot
pedal. The filling machine will remove the cap,
fill to the desired volume and replace the cap
into the final closed position
• The fill connector is a high throughput fluid path
and is standard across all BPC sizes (100 mL,
250 mL, 500 mL, 1 L, 2 L, 5 L, 10 L, 20 L)
BPC and equipment interface
45
Case Study
Conversion of a Traditional Facility Into a Flexible Facility
Situation Our Response Value Delivered
• Customer’s choice between
investment in additional stainless
steel facility or SUT
• High upfront cost for Stainless
Steel systems
• Long set up times & down times
during change-over
• Difficult to change when market
conditions change
• Introduced 500L S.U.B.
• Installed 2000L S.U.B.
in phase 2
• Worked with customer to optimize
operating conditions
to maximize titers
• Customer experienced 85%
reduction in capital equipment
investment
• 2000L S.U.B. performance closely
matches performance at bench
and 500L scale
• Ability to build out smaller
footprint facility
• Simplified personnel and
material flow
46
Case Study
Increased Productivity & Reduction in Capital Investment
Situation Our Response Value Delivered
• A large Animal Health company is
using micro carriers
• But it’s very difficult to remove
from stainless steel parts
(i.e., impeller and various ports)
• In a single-use bioreactor, this
difficulty is resolved as all micro
carriers from the previous
production are disposed.
We were selected based on the
following:
• SUT construction materials, like
bag sterility, splash proof,
resistant to routinely used
disinfection methods
• Reliability and maintenance of
products
• Meeting critical control
parameters, like pH, dO2,
stirring speed
• Architecture incl. volume range,
dimensions (500L S.U.B.)
• > 80% capital investment saving
compared to purchase of
stainless steel system
• Virus yields in the 250L S.U.B.
are equal or better than the ones
obtained in reference bioreactors
47
Your Team
BioProduction Account Manager
Single-Use Cell Culture Purification Analytics
• Sales
Name:
Contact:
• Technical Expert (FAS)
Name:
Contact:
• Sales
Name:
Contact:
• Technical Expert (FAS)
Name:
Contact:
• Sales
Name:
Contact:
• Technical Expert (FAS)
Name:
Contact:
• Sales
Name:
Contact:
• Technical Expert (FAS)
Name:
Contact: