Single-Use vs.

Stainless Steel
A Planner’s Perspective

Dr. Wolfgang Minas

Chemgineering Technology AG
wolfgang.minas@chemgineering.com
T +41 61 467 5449

The Business Designers | The Technology Designers

Outline
 Scope of presentation
 Considerations for planners
 Examples
 Conclusion and outlook

Disclaimer: Chemgineering has no relation or commercial interest with any of the

equipment supplier mentioned in this presentation, and pictures of equipment are
solely shown as examples or for demonstration purpose.

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Scope of presentation
Focus is pilot and industral scale production equipment for use in
(bio)pharmaceutical production:

 Bags and container systems

 Compounding solutions
 Single-use bioreactors
 Single use columns
 Single use UFDF (TFF) solutions
 …

Not in focus is:

 Laboratory material
 Medical devices

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As planner - developing the solution
 Knowing the critical process parameter
 Define the requirements vs nice-to-have options
 Knowing the available technologies
 Knowing the limits of the technologies

Always stay well within the limits of a technology

Do NOT count on solutions under development
Count on the expertise and experience from existing solutions

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Planning Consideration on …
 Process level
 Site/facility level
 Strategic level
 Regulatory level
 HR level

 defining the best fit for the operator/client

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Process Considerations
 New process with development options vs registered process
 Scale (< 2’000 l >), number of batches, buffer volumes
 Dedicated production or multiproduct facility, integration into existing process
 Number of product changes
 Process requirements (temp, pressure, solvents, inertization)
 Process technology (e.g. filtration vs centrifugation)
 Transfer lines
 Risk of leakage (product value and/or (bio)hazard)
 Infrastructure requirements (containment, (bio)hazard, Ex. OeL)
 Risk for human error manual operations and handling vs fully automated
operation
 Cleaning/prerinsing requirements for non-disposable and disposable material
 CIP and SIP requirements
 Waste handling (decontamination requirements, disposal)

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Site Considerations
Green field planning or Integration into existing space/process:

 Existing process infrastructure (utilities and energies)

 Connections to other installations (bulk production  filling)
 Technical installations in the clean rooms
 Product storage and transportation requirements (temp, pressure, shocks, …)
 In process space requirements for material storage, delivery (into production)
and decontamination/disposal
 Site traffic for deliveries
 Site logistics and warehousing, material handling, inspections and release

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Planning for Process & Process Infrastructure
 Production site Layouts differ
 Space to moving and placing container vs fix installed tanks
 Decontamination of used plastic ware in autoclaves vs CIP/SIP

 Process media requirements differ

 Possibly no central installations for clean steam or WFI
 Possibly no washing areas needed

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Process media
Clean steam:
 HAVC system (humidification for clean rooms)
 SIP operations
 Sterilization autoclaves
WFI:
 Compounding, buffer preparation
 Final rinse in CIP and in washing machine
 Cleaning of production area
PW:
 Clean steam and WFI generation
 Washing and CIP
 Compounding media
 Cleaning of production area

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Strategic Considerations
 Invest costs / cash flow / short, mid, long terms strategies?
 Modular design options
 Speed to implement / delivery times
 Time to market

 Currently no standards for single use equipment / sensors

The client decision for a specific system means bonding for a long term with a
single supplier  risk analysis!
Switching of supplier currently requires changing the hardware (totes)
 Disposal strategy
 Supply chain:
 just in time delivery vs local storage capacity

COGS based on local / site constraints

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Regulatory Issues
 Stainless steel installation require CIP/SIP and validated cleaning. This can
be an issue (carry over) in a multiproduct environment with frequent product
changes and/or handling of highly potent biopharmaceutical drugs.
 Hard piped installations require qualification and re-qualifications
 Hard piped installation contain sensors requiring recalibration.

 Single use equipment and material requires qualification and incoming goods
inspections and releases.
 Single Use material may require rinsing/flushing/washing and sanitization
prior use: Pre-rinse of filters, washing of carboys, etc.
 Single use films and tubing may ‘breath’ and may leach material in to the
product. Therefore leachables and extractables but also gas exchange with
the environment require analysis and documentation.

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Giving away control but still being accountable!
Government agencies hold the producers accountable.

For steel systems, companies have a history, validated processes and hence the
overall control and responsibility for the process and the product quality.
With single-use, a lot of control is given to the suppliers, but the full responsibility
remains with the end user!

Users need:
understanding how single-use products are made, measured and released;
to have well-defined materials of construction;
to be confident that the single-use product won’t negatively impact the drug
substance, drug product
to meet the regulatory requirements
asking suppliers to match the clean room classifications to the applications of
the end users – a key piece is the environmental monitoring

BioProcess International in Boston 2014

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Human Ressources – changing workloads
Changing to single-use processing:

More manual process operations

More warehousing
More site traffic (deliveries)
Less or smaller infrastructure
Less maintenance
Less requalifications

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Today – supplier side
Nearly all equipment supplier for DSP equipment provide the choice
between traditional hard piped equipment and single use solutions for
‘mainstream’ processes.
The traditional bioreactor builders have not entered the SUB market.

 Numerous designs for bags (round, square, w / w/o mixing), container/totes,

SUBs etc. exist.
 Temperature control options for compounding systems
 Different mixing system designs
 Customized design of single-use flow paths an connections are offered
 Different solutions for sterile connecting and disconnecting exist.

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Bioreactor - from lab to large scale production

Scalable from ~5l to 250 m3

High mixing,
Good heat transfer
Suitable for high viscosity media
Fully automated operation,
Incl. CIP, SIP, transfers
No need for clean rooms
Containment ensured
Higher invest cost
Flexibility limited
Longer lead times
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Single Use Bioreactor from lab scale to ~ 2’000
liter

Focus on cell culture

Autonomous operation gives flexibility
No CIP or SIP needed,
Limited interfaces to process media
Scale ~0.1 to 2 m3
Positioned in clean room
Heat transfer limited
Mixing limited
Risks for leakage
Manual set up and connections
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DSP – chromatography (Columns)

Column diameter 0.20 – 3 m common in production

Scalable up to >30 m3
Preparative HPLC possible
Packing with any matrix possible by user
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DSP – chromatography (Columns)

Pre-packed columns
Single use flow path systems
Separation matrix is always process specific
Limited room for customer specific solutions
Limited scalability
Limited range of process parameter
Flow path is customized
Customized solutions require commitment to min. order sizes
More manual interactions

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DSP – TFF systems

The filtration matrix and type is always process specific

Limited room for customer specific solutions
Limited scalability
Limited range of process parameter
Minimum system volume/dead volume
Flow path is customized
More operator interactions
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Recent developments
Single use pump heads

Single use valves

Single use centrifuges

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Other Developments / Needs
 Aseptic re-connections
 Welding
 Proprietary solutions
 All for operations in clean room environments

 Aseptic connections in hybrid systems (steel – plastic)

 Customized solutions for steaming through connections involve
manual manipulation of sterilized tubing, e.g. by adding a valve

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Example: Tech Transfer from USA to Europe

Initial Concept, use of disposables except bioreactor for microbial fermentation:

 Small equipment dedicated clean steam generator for fermenter and
autoclave
 No central WFI or PW generation, storage and distribution
 5-7 FTE

process transfer and challenge:

 2-3 FTE in Europe
 Cleaning, sterilization and decontamination concept made 2 autoclaves and a
washing machine, and in process waste water inactivation necessary
 Waste water inactivation

 WFI & PW storage and distribution and clean steam was needed despite
single use technology.

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Hybrid solutions
 Most clients require a hybrid solution combining single use and hard piped
installations.

 Because clients expect customized equipment for biotech applications

(sensors, flow path, shear stress ….)
 Because clients require interfacing with other sites/customers 
coordination of interfaces
 Changing an existing process may have regulatory consequences (time
and costs)

 Most clients refurbish an existing building or need to integrate into the site
infrastructure (e.g. warehousing)

 Infrastructure for cleaning and sanitization of non-disposable material still

needed

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Our Conclusions
 As independent planner we evaluates the aspects mentioned to
develop the best solution for the respective project, primarily reflecting
the process needs, the production model and the given situation on
site.
 Serving many customers, we use the feedback and experience from
various projects and processes to integrate this knowledge into new
projects.
 Either technology has its Pros and Cons, and it is most critical to
understand and observe its limits.
 The unbiased contact to the suppliers is valuable.
 Knowing the possibilities, following new developments and
understanding the client’s processes

 finding the best solution

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Vielen Dank

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