pda annual meeting 2010 - single-use technology up-date
DESCRIPTION
Single-use technology becomes an essential part of the biopharmaceutical industry and is nowadays not any-longer just a thought, but a planned activity, especially when new process or facilities are planned. It creates the flexibility and processing speed required by the industry.TRANSCRIPT
PDA Connecting People, Science and RegulationSM
Disposable Biopharmaceutical ProcessesAdvances & Benefits
March 15-19, 2010, Orlando, FL
Maik W. Jornitz & Thomas Paust, Sartorius Stedim Biotech
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Agenda
Benefits of Disposability
Existing & Emerging Single-use Technology
Example Cases
Conclusion
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Benefits of Disposability
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Benefit – Risk Reduction
Risks (drug efficacy, approval)
CAPEX Motivation
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MediaMedia Filtration
Media Bags
Upstream
BioReactors
HarvestingContaminant
Removal
Fermentation/Cell Culture
Concentration TargetPurification
Purification
Viral Removal
SterileFiltration
Form/Fill
Buffer Prep/Filtration
$ k $ M $ M $ k $ kPossible Investment Costs$ k - MPossible Validation Costs
Potential Costs for a Process per m²: $ 60 - 100
Source: S.J. Tarnowski, PhD, ImClone, San Diego, 2001
Benefit - Capital Investment Reduction
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Benefit – Set-up Time ReductionExample: Cell Culture Media Hold
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Benefit – Cleaning/Protection of the End-userIncreasing Potency of Drug Products
Fraction of Daily Dose Permitted
Topical products 1/10th-1/100th Oral products 1/100th-1/1000thInjections, 1/1000th-1/10,000thophthalmics
Research, 1/10,000th-1/100,000thinvestigationalproducts
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 LimitationsVolume [L]
Phases
104
103
102
101
100
10-1
Development Pilot Phase III/ProductionClinical Material (Phase I – II)Screening
Trends:Higher Expression Rates
Increasing Titers & Personalized Medicine
Reduction inProcess Volume10-2
hybri
d syst
ems
multi-u
se sys
tems
single
-use s
ystem
s
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Existing Technology – Benefits vs. ShortcomingsBenefits
☺ Reduced CAPEX
☺ Reduced cleaning
☺ Minimal set-up
☺ Reduced down-time, i.e. increased equipment utilization
☺ Reduced foot-print needs
☺ Increased flexibility/multi-purpose use
☺ End-user protection
Shortcomings
Extractable/Leachable
Scalability (in instances)
Mechanical strength
Sensor stability
Performance comparability
“The great unknown”
Source: Aspen Brook Consulting, 2009
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Existing & Emerging Single-use Technologies
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Source: ATMI
Existing – Single-use Process Components
Source: Pall
Source: GE Healthcare
Source: Xcellerex
Source: Millipore
Source: Sartorius Stedim
Source: ThermoFisher
Source: Cuno
Source: NewAge Industries
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Emerging – Single-use Unit Operations
Source: Sartorius Stedim
Source: Millipore
Next Integration of SUUnit Operationsto a Process ?!
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Single-use Technology Positions (comparison of SU technologies)
Low Level of Experience High
High
Levelof
Use
Low
Filter Capsules
PolymericTubing
RFID
UnitOps.
SUBags
SUMixing
Chroma-tography
Bio-reactor
Connector
SUValves
SUPumps
SUSensors
SUFilling
Technology & Experience Trend
SUTFF
Source: Aspen Brook Consulting, 2009
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Validation/Qualification Requirements
γ Sterilization Validation
Extractables Analysis
Actual Product Contact & Duration
RP-HPLC, GC-MS, FTIR
USP Class VI
Chemical Compatibility Physical Testing
Burst TestLeak Test, Seal Strength Film Thickness
Endotoxin Testing
Permeation Analysis
Long-term Shelf Life
Unspecific Adsorption
Particle Release
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)
Source: BioPharm Services
60 % of the costsof a re-usable system
Major cost component:Water,also a common major bottleneck
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Cleaning/Set-up Delay Impact (actual case)
Biotech facility produces max 4 batches, often only 3Each batch has an estimated market value of $ 30 Mio
It turned out the bottlenecks are holding tanks:Cleaning/Set-up/Sterilization Time > 8 hoursadditional rinse WFI availability limitations
A disposable holding and/or mixing systemwould be set-up in minutes
This improvement would mean:min 1 batch more/week $ 1.5 Bio additional revenue
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Single-use vs. Multi-use (time to implementation)
Source: Stephen Brown, Vialis, PDA/EMEA Meeting 2009
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
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Costs of Polishing: Resin or Membrane ?Anion exchanger polishing step (flow through) for the removal ofDNA, HCP, Protein A and endotoxins
Source: Gottschalk, PhD
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Cost Evaluation Tools
End-user Information
- Type of Process(e.g. mAb)
- Brief Process Description(e.g. Block schematic)
- Basic Process Data (# Batches, Titre, ...)
- other InformationsOutput for end-user
- Process Flow Diagram
- Equipment List
- Standard Layout Studies
- Total Investment Cost
- Capital investment
- Operational costs (disposables vs. re-usable)Vendor input
- Equipment Data
- Pricing Informations
- Process Know-how
- Process Pattern
- Other information
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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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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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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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A pessimist sees the difficulty in every opportunity;
an optimist sees the opportunity in every difficulty.
Sir Winston Churchill
[email protected]@Sartorius-Stedim.com
Thank you