Single Use Technologies – Overview and Business Drivers
PDA Single use systems for Pharmaceutical Applications. Melbourne 20th March 2012
Luke Heaven – Director of Marketing (EU/Asia/NEMEA/Cuba)
1. Introduction
2. Business Drivers for SUS
3. Single-Use Today
4. Summary
Biotech Becomes Predominant Vs Pharma
Innovation Drivers mAb’s and Vaccines
Biotech Drugs in Development by Product Category*
Vaccines
298
mAbs
300
Rec Proteins
78
Gene therapy
54
Cell therapy
64
Antisense
23
Interferons
20
Interleukins
10
Growth factors
10
Others
• >50% of newly approved drugs are biotech drugs
• mAb’s targets mainly asthma, Crohn’s disease,
rheumatoid arthritis, or various types of cancer
• Therapeutic vaccines development (AIDS, cancer)
• mAb’s & vaccines show a strong trend towards
SUS
45
0
50 100 150 200 250 300 350
Source: PhRMA 2011 Report Medicines in Development – Biotechnology
* of America‘s leading pharmaceutical research and biotechnology companies
Future Biopharmaceutical Markets
The most interesting target products for the next future in the biopharmaceutical
industries are :
•
Monoclonal Antibodies (mAbs)
•
Therapeutic Proteins
•
Vaccines
The biopharmaceutical market, estimated value and forecast 2009-2015 (Billion $) is
shown in the Table below.
2009
2010
2011
2012
2013
2014
2015
Annual Growth
%
MAbs
38
41
45
50
55
59
64
6,30
Therapeutic
Proteins
61
63
66
69
72
75
78
4,40
Vaccines
18
19
21
23
25
26
28
8,10
Total Market
117
123
132
142
152
160
170
6,70
Year
Source: Business Insights Ltd.
Source: Future Marketing and Sales Opportunities in the Asia Pacific Region, Detlef Lobas – Sartorius Stedim Biotech, 2011
Biotech Processes – Unique Attributes & Needs
• High potency drugs have extraordinary cleaning requirements
• End-user protection has an elevated focus
• Process utilization optimization by multi-purpose use
• Low investment motivation due to high risks of success
• Flexible small scale development process designs
• Fast turn-around and set-up for process capacity increases
• Ease-of-use to assure failure rate reduction
Biotech Industry‘s Challenges
Focus Shift from Kg’s to Cog’s
• Facing the small molecule challenge of the past
‐ Price pressure and affordability call for significant reduction of costs
‐ Need for process improvement Vs complex regulatory
‐ Manufacturing capacity utilization is too low, i.e. ~ 60%
‐ Entrance of Biosimilars Vs patent expiration
•
Global market shows regional capacity developments
‐ Manufacturing capacity increase in Asia with multiple green field projects
‐ Mergers, restructuring and capacity adjustments in Europe and NA
‐ mAbs and Biosimilars pipeline in LA
• Technology platform approaches for single-use (SUS), hybrid (HS) and multi-use
(MUS) systems
1. Introduction
2. Business Driver for SUS
3. Single-Use Today
4. Summary
The Drivers in Bio- Pharmaceutical Processes
Safety
No
Cross
contamination
Speed
Value benefit
Process economics (CIP)
Efficiency
DifferentStarting Material
Expression Systems
Quality
The Single Use Market
Benefits of Single Use Technologies are Well Known
Economic Benefits
• Reduce capital investment & commissioning time
• Minimize CIP/SIP validation, utilities & labour
• Reduce foot print & speed up time to market
Improved Safety
• Enhanced user protection via closed systems
• Reduced risk of cross contamination
Flexibility
• Optimize facility layout
• Easy turn around and changeover
• Improved capacity utilization
Biotech Industry
Process Improvement Enable Mass Adoption of Single Use

The Biotech industry has driven the adoption of Single-Use
products,

New trend toward single use unit operations & entire
bioprocesses

Improvement in Protein titers and downstream purification
yields are the major enabling factors
•
‐
Protein titers growing from < 1g/l to > 5g/l
‐
Yield improvement from 30% to >60%
‐
20.000L process scale down to 2.000L
Single Use BioProcess facility become a reality
When to Apply – Single-use, Hybrid or Multi-use Systems (SUS, HS,
MUS)
Hybrid Systems linking Stainless Steel and Disposable Systems
•
•
•
•
Product wetted materials stainless steel
Hard piped
Transfers by overpressure
SIP and CIP required
•
•
•
•
•
•
•
•
Starting point for Hybrid Systems are normally Stainless Steel Systems
Implementation of Disposable (Single Use) sub-systems where feasible
Implement standardized interfaces between stainless steel and plastics
SIP and CIP for connecting points only
Product wetted materials from plastics
Connections by flexible tubing
Transfers by peristaltic pumps
SIP and CIP not required
Drivers for Revamping Projects in Biopharmaceutical Manufacturing
•
Life Cycle of installed plants expired
- Stainless steel 20 to 25 years
- Instrumentation and automation 10 to 15 years
•
Higher automation level for manual operated plants
- Change manual valve actuators to pneumatic actuators
•
Added functionality resulting from process optimization
- e.g. additional feedings / fed batch for cell culture processes
•
Product changes in DSP processes
- Sizing of process equipment not suitable for changed product titers
Utilization of Single-Use Systems in Revamping Projects
•
Faster realization time by using “of the shelf” pre-engineered equipment
•
Less automation, however more manual operations required
•
Main applications are addition systems for all kind of media
- Less complex than fixed piped stainless steel addition vessels
- Avoid implementation of CIP for old plants
•
Replace mobile stainless steel process vessels by mobile bag containers with bags
- No SIP and CIP required
•
Use mobile bags as the transfer system for product
•
Allow variability in bag size, especially in DSP processes
Case Study: Fermentation Expansion Project - Stainless Steel version 50 L
Substrat
Mobiltank
LD
200 L
Lauge
Mobiltank
LD
Kleinmenge
6L
AS
Kleinmenge
12 L
Lauge
Kleinmenge
RD
RD
NaOH RD
RD
B3730
SK
RD
RD
LD
120 L
AS
LD
NaOH RD
RD
A
RD
B3740
RD
SK
700 L
Substrat 1
700 L
Substrat 2
A
RD
RD
SK
B3630
B3610
RD
B3620
SK
6L
AS
SK
BA BA SK BA
SK
B3710
B3720
RD
50 L
Substrat
J
A
NaOH
RD
120 L
AS
BA BA SK BA
12 L
Lauge
SK
SK
240 L
Lauge
BA SK BA
BA
SK
SK
BA SK BA
M
M
M
RD
SK BA
M
M
RD
SK BA
SK BA
RD
SK BA
RD
SK BA
RD
SK BA
SK BA
RW
NaOH
RW
NaOH
A
A
RD
BA SK
Medienansatz
B7020
RD
BA SK
G
RD
RD
Medium
20 L
Lauge
2L
H
AS
1L
SK
BA
BA
2600 L
Dialyse
Fermenter
SK
SK
C3600
Modul 1
SK SK
200 L
Medium
AS
1L
Lauge
10 L
SK
R
RD
AS
5L
Substr.
50 L
SK
T
RD LD
LD
Medium
200 L
Lauge
5L
10500 L
Dialyse
Medium
RD LD
SK
300 L
Vorfermenter
RD
Weld
Medium
50 L
10500 L
Dialyse
Medium
S
RD
C3500
50 L SUB-Vorfermenter
RD
SK
RD
Modul 2
Weld
Weld
B3800
SK
SK BA
J
RD
RD
Weld
B3750
C3700
M
M
SK
M
Substr.
10 L
M
RD
RW
RD
B
SK
BA
BA SK
RD
RD
NaOH
B
B
HBA SK BA
HBA SK BA
B
NaOH
BA SK BA HBA
Weld
Weld
Weld
Weld
Weld
Weld
Weld
SK SK BA HBA
Ernte
B6510, B6520
RD
Weld
T
SK
Weld
RD
SK
C4600
600 L SUB-Vorfermenter
C4500
50 L SUB-Vorfermenter
Weld
SK
BA
RD
Medienansatz
B7040
C
SK
BA
SK
BA
SK BA
Ernte
B6510, B6520, S6600
Ernte
B6310, B6320, S6300
Case Study: Fermentation Expansion Project – Single-Use version.
120 L
AS
RD
NaOH
RD
500 L
Substrat
1
50 L
Substrat
B3720
500 L
Substrat
2
120 L
AS
SK
200 L
Lauge
BA
10 L
Lauge
5L
AS
M
RD
SK BA
RW
NaOH
RW
NaOH
A
A
RD
BA SK
RD
BA SK
Medienansatz
B7020
Weld
Weld
RD
RD
Weld
Medium
20 L
Lauge
2L
H
AS
1L
SK
BA
BA
SK BA
SK
SK
S
Modul 2
RD
RD
SK
C3600
RD LD
SK
300 L
Vorfermenter
RD
SK SK SK
Weld
SK
T
RD LD
Modul 1
RD
C3500
50 L SUB-Vorfermenter
RD
Weld
SK
Weld
RD
2600 L
Dialyse
Fermenter
RD
Weld
B3800
10500 L
Dialyse
Medium
SK
RD
Weld
Weld
B3750
10500 L
Dialyse
Medium
C3700
SK
SK
R
Medium
200 L
Medium
50 L
Lauge
5L
AS
1L
Medium
200 L
Lauge
10 L
AS
5L
Substr.
50 L
M
Weld
Substr.
10 L
M
SK
M
M
RD
RW
RD
B
RD
RD
NaOH
B
B
HBA SK BA
HBA SK BA
B
NaOH
BA SK BA HBA
Weld
Weld
Weld
Weld
Weld
Weld
Weld
SK SK BA HBA
Ernte
B6510, B6520
RD
Weld
T
SK
Weld
RD
SK
C4600
600 L SUB-Vorfermenter
C4500
50 L SUB-Vorfermenter
Weld
SK
BA
RD
Medienansatz
B7040
C
SK
BA
SK
BA
SK BA
Ernte
B6510, B6520, S6600
Ernte
B6310, B6320, S6300
Case Study: Fermentation Expansion Project - Approach 50 L
Substrat
Mobiltank
LD
200 L
Lauge
Mobiltank
LD
6L
AS
Kleinmenge
12 L
Lauge
Kleinmenge
RD
RD
NaOH RD
RD
B3730
SK
RD
RD
NaOH RD
RD
RD
B3740
700 L
Substrat 2
A
B3610
RD
B3620
SK
6L
AS
SK
BA BA SK BA
SK
RD
A
NaOH
120 L
AS
BA BA SK BA
12 L
Lauge
SK
SK
B3720
B3710
B3720
RD
50 L
Substrat
J
NaOH
RD
RD
B3630
RD
RD
SK
700 L
Substrat 1
A
RD
SK
120 L
AS
LD
120 L
AS
LD
Kleinmenge
500 L
Substrat
1
240 L
Lauge
BA SK BA
50 L
Substrat
BA
500 L
Substrat
2
120 L
AS
SK
SK
SK
200 L
Lauge
BA
10 L
Lauge
5L
AS
M
RD
BA SK BA
M
M
M
RD
M
M
RD
RD
RD
RD
SK BA
SK BA
SK BA
SK BA
SK BA
SK BA
SK BA
SK BA
RW
RW
NaOH
NaOH
RW
RW
NaOH
A
NaOH
A
A
A
RD
RD
BA SK
Medienansatz
B7020
BA SK
RD
RD
BA SK
Medienansatz
B7020
BA SK
G
Weld
Weld
RD
RD
RD
RD
Weld
H
AS
1L
BA
BA
RD
2600 L
Dialyse
Fermenter
SK
Modul 2
SK
C3600
H
AS
1L
Lauge
10 L
Substr.
50 L
Modul 1
SK SK SK
Weld
M
SK
M
SK
BA
BA SK
Medium
50 L
M
RD
RW
RD
NaOH
Weld
Weld
Weld
Weld
SK
Lauge
5L
AS
1L
Medium
200 L
Lauge
10 L
AS
5L
Substr.
50 L
M
Weld
Substr.
10 L
M
SK
M
RD
B
B
HBA SK BA
SK SK BA HBA
BA SK BA HBA
HBA SK BA
Ernte
B6510, B6520
RD
Weld
Weld
Weld
Weld
Weld
Weld
Weld
Weld
Weld
B
B
HBA SK BA
HBA SK BA
B
SK SK BA HBA
Ernte
B6510, B6520
RD
Weld
T
SK
RD
C4500
50 L SUB-Vorfermenter
SK
BA
RD
SK
C4600
600 L SUB-Vorfermenter
SK
Weld
RD
RD
NaOH
T
SK
C4600
600 L SUB-Vorfermenter
C4500
50 L SUB-Vorfermenter
M
RD
RW
RD
B
NaOH
BA SK BA HBA
Weld
SK
T
SK
RD
B
NaOH
Weld
RD LD
SK
RD LD
R
Medium
200 L
M
Substr.
10 L
B
Weld
SK
C3600
300 L
Vorfermenter
RD
R
RD
AS
5L
SK
RD
SK
RD
S
RD
Weld
SK
C3500
50 L SUB-Vorfermenter
RD
2600 L
Dialyse
Fermenter
SK
RD LD
LD
Medium
200 L
AS
1L
Weld
B3800
10500 L
Dialyse
Medium
SK
SK BA
RD
Weld
RD LD
RD
SK SK
200 L
Medium
BA
RD
T
B3750
10500 L
Dialyse
Medium
C3700
BA
Weld
SK
SK
300 L
Vorfermenter
RD
Weld
Lauge
5L
Lauge
2L
Weld
S
RD
RD
C3500
50 L SUB-Vorfermenter
Medium
50 L
Medium
20 L
SK
RD
SK
RD
Weld
Weld
B3800
10500 L
Dialyse
Medium
SK
SK BA
J
Weld
B3750
10500 L
Dialyse
Medium
C3700
SK
Modul 2
Lauge
2L
Modul 1
Medium
20 L
Weld
Weld
SK
BA
RD
RD
Medienansatz
B7040
Medienansatz
B7040
C
SK
BA
SK
BA
C
SK
SK BA
BA
SK
BA
SK BA
Ernte
B6510, B6520, S6600
Ernte
B6510, B6520, S6600
Ernte
B6310, B6320, S6300
Ernte
B6310, B6320, S6300
•
Seed fermentation train with Disposable Bioreactors (50L, 500L Rocker Systems)
•
Keep all addition vessels that need in situ sterilization of media as stainless steel vessels
•
Keep all media vessels > 500L as stainless steel vessels
•
Replace all addition vessels with sterile filtration of media by moveable bag containers
•
Delete all mobile vessels for transportation from media preparation to process area
Case Study: Fermentation Expansion Project - Cost Comparison 50 L
Substrat
Mobiltank
LD
200 L
Lauge
Mobiltank
LD
6L
AS
Kleinmenge
12 L
Lauge
Kleinmenge
RD
RD
NaOH RD
RD
B3730
SK
RD
RD
NaOH RD
RD
RD
700 L
Substrat 2
A
B3610
RD
B3620
SK
6L
AS
SK
BA BA SK BA
SK
RD
A
NaOH
B3710
B3720
RD
50 L
Substrat
J
NaOH
RD
RD
B3630
RD
RD
B3740
SK
700 L
Substrat 1
A
RD
SK
120 L
AS
LD
120 L
AS
LD
Kleinmenge
120 L
AS
BA BA SK BA
12 L
Lauge
SK
SK
240 L
Lauge
BA SK BA
500 L
Substrat
1
50 L
Substrat
BA
B3720
500 L
Substrat
2
120 L
AS
SK
200 L
Lauge
M
SK
SK
BA
10 L
Lauge
5L
AS
RD
BA SK BA
M
M
M
RD
M
M
RD
RD
RD
RD
SK BA
SK BA
SK BA
SK BA
SK BA
SK BA
SK BA
SK BA
RW
RW
NaOH
RW
NaOH
A
NaOH
RW
NaOH
A
A
RD
BA SK
Medienansatz
B7020
RD
BA SK
Weld
G
H
AS
1L
BA
SK
2600 L
Dialyse
Fermenter
RD
SK
Modul 2
SK
C3600
Medium
200 L
Lauge
10 L
Substr.
50 L
RD
M
Modul 1
SK
M
SK
BA
BA SK
Weld
Weld
Weld
Weld
Weld
T
SK
Lauge
5L
AS
1L
Lauge
10 L
AS
5L
Substr.
50 L
M
Weld
Substr.
10 L
RD
M
B
B
BA SK BA HBA
HBA SK BA
SK SK BA HBA
Weld
HBA SK BA
M
RD
RD
B
B
HBA SK BA
HBA SK BA
B
Weld
Weld
Weld
Weld
Weld
Weld
SK SK BA HBA
Ernte
B6510, B6520
RD
Weld
Ernte
B6510, B6520
RD
Weld
M
RD
NaOH
NaOH
T
T
SK
RD
Weld
SK
Weld
RD
SK
C4600
600 L SUB-Vorfermenter
C4500
50 L SUB-Vorfermenter
SK
C4600
600 L SUB-Vorfermenter
Weld
SK
SK
RD
SK
C4500
50 L SUB-Vorfermenter
RD LD
RW
M
RD
B
B
NaOH
BA SK BA HBA
SK
Medium
200 L
RD
NaOH
10500 L
Dialyse
Medium
RD LD
R
Medium
200 L
RW
RD
SK SK SK
Weld
Medium
50 L
M
Substr.
10 L
10500 L
Dialyse
Medium
S
SK
SK
R
RD
AS
5L
C3500
50 L SUB-Vorfermenter
RD
SK
SK
300 L
Vorfermenter
RD
SK
RD LD
RD
2600 L
Dialyse
Fermenter
SK
SK
C3600
SK
B3800
SK
SK BA
RD
Weld
RD
T
SK SK
B
Weld
BA
Weld
RD
Weld
RD LD
LD
AS
1L
Weld
Weld
S
300 L
Vorfermenter
RD
200 L
Medium
Weld
Weld
BA
SK
SK BA
SK
RD
RD
C3500
50 L SUB-Vorfermenter
Lauge
5L
B3800
10500 L
Dialyse
Medium
RD
BA
J
Weld
B3750
C3700
C3700
SK
RD
RD
Medium
50 L
B3750
10500 L
Dialyse
Medium
H
AS
1L
Modul 2
Lauge
2L
Weld
Lauge
2L
Modul 1
Medium
20 L
RD
Weld
Medium
20 L
Weld
RD
BA SK
Weld
RD
RD
RD
A
RD
BA SK
Medienansatz
B7020
SK
Weld
BA
RD
BA
RD
Medienansatz
B7040
Medienansatz
B7040
C
C
SK
BA
SK
BA
SK BA
SK
BA
SK
BA
SK BA
Ernte
B6510, B6520, S6600
Ernte
B6510, B6520, S6600
Ernte
B6310, B6320, S6300
Ernte
B6310, B6320, S6300
Item
Stainless Steel
Single Use
Savings
Mechanical Equipment
23,4 %
18,1 %
23%
Instrumentation and Control
21,8 %
17,1 %
22%
Manufacturing and Installation
27,9 %
21,9 %
22%
Engineering and Qualification
26,5 %
22,1 %
17%
0,4 %
0,3 %
21%
100,0 %
79,4 %
21%
Transportation
Total
1. Introduction
2. Business Drivers for SUS
3. Single-Use Today
4. Summary
Next Step – is active...
Production Sites using single-use & containment technology to produce, for
example, a vaccine at the point-of-use
Bioreactor
Sampling
Preparation
Cell Removal
Clarification
Virus
Sterile
Inactivation Filtration
Recirculation
Storage
Crossflow
Volume Reduction
Seed Bioreactor
Sterile
Filtration
Storage
Bioreactor
Preparation
Freeze-thaw Bags
Monitoring & Control
Storage
Form and Fill
Crossflow
Concentration|Diafiltration
Affinity Chromat. Low pH Virus
Capturing Step
Inactivation
Polishing 1 Polishing 2
Membrane Chromat.
Sterile
Crossflow
Buffer Exchange Filtration
Controlled
Freeze-thaw
System
Single-Use Technologies
Bag Technologies
storage
dosing liquid
mixing
powder additions
Purification and Filtration Technologies
depth filtration
cross-flow (UF/DF/MF)
membrane filtration
membrane adsorbers
Connection and Disconnection Possibilities – Full Range of
Applications
Connection Technologies
Steam connectors
.
Heat Welding
.
For Steam to
or Steam
Through
For Most
Tubings
Used in hybrid
solutions
Disconnection Technologies
Aseptic Connectors
Heat Sealing
.
For
Thermoplastic
Tubings
Mechanical
For Most Tubings
Dry or wet
connection
Membrane or
Mecanical
Mechanism
For
Thermoplastic
Tubings
Radio Frequency Sealer
.
.
For most tubings
Consists of a
disposable
element and Tool
Capable of
Disconnecting
EVA, PVC
Tubing
Single-Use Technologies
Aseptic Transfer Systems
Single Use Technology Adoption Model
Single Use Adoption
(Volume)
Technology
Evaluation
Process design
Early Commercial
Mature Commercial
Clinical phase III
Production
Production
Process
Development
CTO & STD
CUSTOM / CTO
ETO & CTO
STD & CTO
0,5 to 2 Years
0,5 to 4 Years
1 to 3 Years
> 10 Years
Newest Requirements in the Single Use Market
Summary From most recent Industry Surveys
1.
Product quality, robustness and integrity
2.
Product delivery reliability & long term assurance of supply
3.
Change control with timely notifications & comparability
protocols
4.
Product & technology portfolio with superior performance
5.
Standardization & Technology Integration with improvement
on scalability & ease of use
6.
Documentation & technical support: Qualification test, QC
test, validation & training support
Quality, assurance of
supply & change
control
Technology
development &
Integration
Technical
Documentation &
Support
Single-use Technology Next Moves
High
Polymeric
Tubing
SU
Bags
Filter
Capsules
Connector
SU
Mixing
Level
of
Use
Chromatography
SU
TFF
Bioreactor
SU
Sensors
SU
Pumps
SU
Valves
Unit
Ops.
SU
Filling
RFID
Low
Low
Level of Experience
End-user requirements create innovative opportunities
High
Application Driven Unit Operations
•
The Market Development as brought about new innovations
in Application Driven Unit Operations to assure highest
flexibility
•
These innovations increase the standardization level and
allow Qbd in a ‘plug and play‘ package
•
Introduction of single-use probes to allow Process Analytical
Technology (PAT) approaches in single-use arena
•
Realization of automation concepts to achieve operational
excellence
•
Assurance of process performance, safety, quality & security
of supply is maintained though strategic co-operation
intitiatives between technology owners
Example - Set-Up of the mixing unit
WFI
1. Insert mixing bag assembly
into bag holder
Media
(powder)
2. Move mixing system on floor scale
 The mixing unit is ready for buffer preparation
Example - Set-Up of the storage unit(s)
1. Insert storage bags
into bag holder
 The storage unit(s) are ready to be connected with the mixing bag assembly
Example Operation: Automated pump stop after fluid transfer by weight control
Pump
activated
Pump
Stop
 Automated pump stop after filling
the particular storage bag !
Robustness of Single Use Assemblies
Single Use Systems are built from multiple
components assembled together to provide the
expected design & functional requirements
 Product robustness relies on
- The Quality and Robustness of the Film Material
- The quality of each component & raw material
- The validation of each assembly
 Security of supply relies on
- The supply chain,
- The material specification
- The change control policy
Documentation
Validation & Extractable data
Mechanical properties
Barrier properties (ASTM)
Integrity
Biocompatibility (USP, EP)
Physico-chemical test
Stability test in WFI
Chemical resitance (ASTM)
Gammasterilisation (ISO111137)
Extractable
Bacterial ingress testing
Documentation
Product Certificates of Release
Lot release tests
Monitoring tests
Bacterial Endotoxins test
USP<85> and E.P. 2.6.14
100% visual testing of bag
and seal
USP<788> and E.P. 2.9.19
: Particulate
100% air pressure leak test
(where possible)
ISO 11737: Bioburden
Technical drawing
compliance
ISO 11137: Sterilization of
Medical Devices
ISO 14644: Cleanrooms
environmental controls
Dimensional check
Packaging and labelling
inpection
Gamma sterilization
Documentation
Mechanical & Physico-Chemical Validation data
Qualification Tests
Tests usually performed after gamma irradiation
Mechanical
Properties
Ultimate Tensile Strength (UTS)
Elongation at break
Secant Modulus at 2%
Toughness, Resistance to tearing
Flex Durability, Impact resistance
Barrier Properties
Barrier to Water Vapour (ASTM F1249)
Barrier to Oxygen (ASTM D3985)
Barrier to Carbon Dioxide (ASTM F2476)
Integrity
Seal Strength Integrity, 100% bag integrity testing
Biocompatibility
USP < 87> Biological reactivity tests, In Vitro
USP < 88> Biological reactivity tests, In Vivo
Physico-Chemical
Tests
European Pharmacopéia (E.P.3.1.5 PE with additives for Containers)
BSE/TSE Status (E.P.5.2.8)
USP < 661 >
Stability of WFI
USP and EP
Chemical Resistance
ASTM D543-06 "Method for resistance of Plastic to chemical
reagents"
Documentation
Gamma Sterilization Validation Data
ISO 11137
PROCESS VALIDATION
STERILIZATION CYCLE
DEVELOPMENT
Establishment
of minimum
Sterilization
dose
Establishment
of maximum
material
compatibility
dose
Reproducibility
of dose
Magnitude &
distribution
1. Bioburden Quantification
2. Bioburden Identification
3. Bioburden Resistance Assessment
PROCESS CONTROLS
MAINTENANCE OF STERILITY
1. Bioburden quantification
2. Identification & resistance
3. Environmental monitoring
4. Dose audit
SHELF LIFE
PRODUCT PERFORMANCES
1. Functional performances
1. 100% Visual inspection of bags
2. Package integrity
2. 100% Package inspection
3. Biocompatibility
3. Endotoxins, particles
4. Sterility
IRRADIATION PERFORMANCE
QUALIFICATION
GAMMA IRRADIATION PROCESS
CONSISTENCY
1. Dose mapping and limit setting
1. Product density
2. Density range and limit setting
2. Min and max irradiation dose monitoring
Documentation
Extractable Validation Data
Extraction
model
Tim
e
HCl (pH < 2.5)
4m
WFI
4m
NaOH (pH >
11)
4m
100% ethanol
4m
TOC quantification
METAL analysis 20 – 500 ppb
VOLATILE leachables or compound (VOC)
 GC/MS: Identification and ½ quantification, 5 – 50 ppb
½ VOLATILE leachables (SVOC)
 GC/MS Identification and ½ quantification, 50 ppb
NON VOLATILE leachables (NVOC)
 LC/MS. Identification and full quantification, 1-5 ppb
1. Introduction
2. Business Drivers for SUS
3. Single-Use Today
4. Summary
How Do Configurable Single-Use Systems Support The Customer Needs ?
1. Reduction in cleaning and sterilization operations
2. Minimization of validation efforts for cleaning validation
3. Reduced risk of cross contaminations
4. Enhanced flexibility through better adoption to multi product scenarios and
product demands
5. Reduced facility construction time
6. Reduced time to market
The “Plug & Play” Concept is Here to Change Biomanufacturing
•
Single use systems can be easily configured
using existing SU platform technologies
•
They are standardized, easy to validate & ready
to use for each process step in Up- and
Downstream Processing
•
Single use systems consist of standardized,
movable hardware equipped with flexible,
pre-sterilized Single-Use process equipment
Thank You For Your Attention !