Presentation about current single-use technologies, its benefits and future outlook

1. PDA Connecting People, Science and RegulationSM
Disposable Biopharmaceutical Processes
Advances & Benefits
March 15-19, 2010, Orlando, FL
Maik W. Jornitz & Thomas Paust, Sartorius Stedim Biotech

2. PDA Connecting People, Science and RegulationSM
Agenda
Benefits of Disposability
Existing & Emerging Single-use Technology
Example Cases
Conclusion

3. PDA Connecting People, Science and RegulationSM
Benefits of Disposability

4. PDA Connecting People, Science and RegulationSM
Benefit – Risk Reduction
Risks (drug efficacy, approval)
CAPEX Motivation
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5. PDA Connecting People, Science and RegulationSM
Benefit - Capital Investment Reduction
Upstream Fermentation/Cell Purification Form/Fill
Culture
Media Harvesting
Bio Target Viral Sterile
Media Filtration Contaminant Concentration
Reactors Purification Removal Filtration
Media Bags Removal
Buffer Prep/Filtration
$k $M $M $k $k
Possible Investment Costs
$k-M
Possible Validation Costs
Potential Costs for a Process per m²: $ 60 - 100
Source: S.J. Tarnowski, PhD, ImClone, San Diego, 2001
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6. PDA Connecting People, Science and RegulationSM
Benefit – Set-up Time Reduction
Example: Cell Culture Media Hold
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Benefit – Cleaning/Protection of the End-user
Increasing Potency of Drug Products
Fraction of
Daily Dose Permitted
Topical products 1/10th-1/100th
Oral products 1/100th-1/1000th
Injections, 1/1000th-1/10,000th
ophthalmics
Research, 1/10,000th-1/100,000th
investigational
products
Source: PDA Technical Report #29
Source: FDA CDER, Florida office, 2009
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Benefit – Environmental Impact ?
Source: Sinclair; Leveen, et.al.; The Environmental Impact of Disposable Technologies, The Biopharm International Guide, 11.2008
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Single-use Limitations
Volume [L]
104
Trends:
103 s Higher Expression Rates
st em Increasing Titers &
sy
id s
102
y br m Personalized Medicine
h ste
sy
e
101 i- us
em
s ult
st m
100 sy
u se
g le-
10-1 sin
Reduction in
10-2 Process Volume
Screening Development Pilot Clinical Material (Phase I – II) Phase III/Production Phases
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10. PDA Connecting People, Science and RegulationSM
Existing Technology – Benefits vs. Shortcomings
Benefits Shortcomings
☺ Reduced CAPEX Extractable/Leachable
☺ Reduced cleaning Scalability (in instances)
☺ Minimal set-up Mechanical strength
☺ Reduced down-time, i.e. Sensor stability
increased equipment utilization
Performance comparability
☺ Reduced foot-print needs
“The great unknown”
☺ Increased flexibility/multi-
purpose use
☺ End-user protection
Source: Aspen Brook Consulting, 2009
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11. PDA Connecting People, Science and RegulationSM
Existing & Emerging Single-use Technologies

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Existing – Single-use Process Components
Source: ThermoFisher
Source: ATMI Source: Millipore
Source: Sartorius Stedim
Source: Cuno
Source: GE Healthcare
Source: NewAge Industries
Source: Pall
Source: Xcellerex
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13. PDA Connecting People, Science and RegulationSM
Emerging – Single-use Unit Operations
Source: Millipore
Next Integration of SU
Unit Operations
to a Process ?!
Source: Sartorius Stedim
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Single-use Technology Positions (comparison of SU technologies)
High
Polymeric
Tubing
SU Filter
Bags Capsules
Connector
Source: Aspen Brook Consulting, 2009 SU
Mixing
Level
of d
Tren Chroma-
Use nce SU
erie
tography
TFF
& Exp Bio-
o gy reactor
hnol
Tec SU
Sensors
Unit SU
SU Ops. Filling
SU RFID
Valves
Pumps
Low
Low Level of Experience High
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15. PDA Connecting People, Science and RegulationSM
Validation/Qualification Requirements
γ Sterilization Validation Endotoxin Testing
Extractables Analysis Permeation Analysis
Actual Product Contact & Long-term Shelf Life
Duration
Unspecific Adsorption
RP-HPLC, GC-MS, FTIR
Particle Release
USP Class VI
Chemical Compatibility
Physical Testing
Burst Test
Leak Test,
Seal Strength
Film Thickness 1- Polyethylene Terephthalate (PET)
2- Polyamide (PA)
3- Ethylene Vinyl Alcohol (EVOH)
4- Ultra Low Density Polyethylene (ULDPE)
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Example Cases

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Single-use vs. Multi-use (water consumption w/o steam needs)
60 % of the costs
of a re-usable system
Major cost component:
Water,
also a common
major bottleneck
Source: BioPharm Services
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18. PDA Connecting People, Science and RegulationSM
Cleaning/Set-up Delay Impact (actual case)
Biotech facility produces max 4 batches, often only 3
Each batch has an estimated market value of $ 30 Mio
It turned out the bottlenecks are holding tanks:
Cleaning/Set-up/Sterilization Time > 8 hours
additional rinse WFI availability limitations
A disposable holding and/or mixing system
would be set-up in minutes
This improvement would mean:
min 1 batch more/week $ 1.5 Bio additional revenue
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19. PDA Connecting People, Science and RegulationSM
Single-use vs. Multi-use (time to implementation)
The time to implement a single-use fermentation system is greatly reduce
in comparison to a multi-use system:
2 - 3 years
4 - 7 months
Main reasons for the 5 fold reduction:
• Qualification of the equipment
• Cleaning validation
• Qualification of set-up
Source: Stephen Brown, Vialis, PDA/EMEA Meeting 2009
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20. PDA Connecting People, Science and RegulationSM
Costs of Polishing: Resin or Membrane ?
Anion exchanger polishing step (flow through) for the removal of
DNA, HCP, Protein A and endotoxins
Source: Gottschalk, PhD
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21. PDA Connecting People, Science and RegulationSM
Cost Evaluation Tools
End-user Information
- Type of Process
(e.g. mAb)
- Brief Process Description
(e.g. Block schematic)
- Basic Process Data
(# Batches, Titre, ...) Output for end-user
- other Informations
- Process Flow Diagram
- Equipment List
- Standard Layout Studies
- Total Investment Cost
- Capital investment
- Operational costs
Vendor input (disposables vs. re-usable)
- Equipment Data
- Pricing Informations
- Process Know-how
- Process Pattern
- Other information
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22. PDA Connecting People, Science and RegulationSM
Possible Process Schematic
Source: Xcellerex
Benefits in this Scenario:
• Lower HVAC ceiling area
• Reduced energy costs
• Contained system design
• Lower risk by human intervention
• High production flexibility
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23. PDA Connecting People, Science and RegulationSM
Possible...?
Production Micro-Sites using single-use technology to produce,
for example, a vaccine at the point-of-use
Source: GE Healthcare
Source: Sartorius Stedim
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24. PDA Connecting People, Science and RegulationSM
Conclusion
Some disposable technology has been used successfully for
decades
Some components and validation requirements still pose the
„great unknown“
New technologies are developed to fill existing process gaps –
a 90% disposable process might be possible
Disposability creates major advantages, by reducing costs,
increasing production utilization and protect end-users
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25. PDA Connecting People, Science and RegulationSM
A pessimist sees the difficulty in every opportunity;
an optimist sees the opportunity in every difficulty.
Sir Winston Churchill
Thank you
Maik.Jornitz@Sartorius-Stedim.com
Thomas.Paust@Sartorius-Stedim.com