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Advantages of Leveraging Disposable Bag Technologies for Process and Facility Optimization

October 20, 2011

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The Major Efficiencies of Disposable Technologies

Single-useBio-container Systems

Traditional Multi-use Technologies (Stainless, Glass, etc.)

Reduction of capital equipment/facility footprint needs

Less requirement for Steam-In-Place (SIP) and Clean-In-Place (CIP) processes

Reduction in validation requirements (equipment/cleaning) etc.

Increased speed-t0-market of products and therapies

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Advantages of Single-Use Process Systems

Product integrity

Ease of use

Production capacity and efficiency is increased

Systems are purchased as needed

Efficient utilization of space

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Typical Quality Expectations

ISO 13985 Certified

All manufacturing is under cGMP guidelines.

Bioprocessing products meet the following:

- Class VI Biological tests for Plastics <USP88>

- Physiochemical tests for plastics <USP661>

- Cytotoxicity <USP87>

- Cell Growth Inhibition

- Hemolytic Effects

Oxidizable Substances

A “Certificate of Conformance” is issued with every product.

All components used in manufacturing are lot number traceable.

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General Facility Considerations

Accessibility, ergonomic requirements

Dimensional clearances, ramps, flooring types

Proximity of scales, coolers, utilities, etc.

SIP, CIP availability

Grey space locations

Operating space requirements

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Major Bioprocess Flow Applications

Media

Formulation,

Filtration, Filling

Cell-culture,

FermentationHarvest,

Separation,

Concentration

Purification

Bulk Storage

and Transport

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Manufacturing

Disposable bag manufacturing is typically in a class 10,000 clean room.

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Scalability of Closed, Single-Use Systems 50ml to 3,000L

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Square tube (usually gusset)

design

50, 100, 200, 500, 1000L and larger

standard chamber sizes

Top / Bottom drain / dip-Tube

designs

Impellers, probes, etc. can also be

included in chambers

Typical Offerings of Large Single-use Bags


Common Single-Use Application Requirements


Medium Formulation & Filling


Filling of Process Fluids

Filter

Tank Liner

Product Bags

Flow path samples

Sterility/purge bag


Filling of Process Fluids: Critical Considerations

Pre-filtration needs

Mixing validation

Formulation and filtration time

Flow rate and pressure

Product stability and compatibility

Filter integrity testing

Sterile/Aseptic connections/seals

Sampling needs/timing and locations


Polling Question

How do you currently fill reagents and /or product

in large-volume batches?

– Closed-system manifolds

– Open aseptic transfer

– Sterile docking of individual bags

– Steam-in-place (SIP) piping to receiving tank


Bioreactor/Culturing Applications

Nutrient or

Supplement Vessel

Bioreactor

Harvest Vessel


Bioreactor Cell-culture Application Critical Concerns

Oxygenation

Sensing (pH, DO, etc.)

Flow requirements

Agitation, mixing

Pressure

Foaming, venting

Nutrient and/or Product Adsorption


Centrifugation & Filtration Concentration


Centrifugation & Filtration Concentration Critical Considerations

Shear from fluid transfer

Foaming issues (trapping protein and shear)

Flow requirements

Tubing hoop strength and/or cavitation

predisposition

Spalling (Internal shedding) of tubing


Chromatography Purification

Buffer A

Buffer B Fraction collection bags


Chromatography Purification: Critical Considerations

Air Entrapment

Adsorption

Flow requirements

Chemical compatibility

Secondary fluid containment


Bulk Storage & Transport


Cold Chain and Freezing Bag with Cassette

Label pouch integral with design

Protective cassette for cryogenic temperature

storage


Bulk Storage and Transportation

Long-term

Storage/Transportation of

Large-Volume Bulk Product

or Intermediates

Frozen or Refrigerated

Processing and

Transportation


Polling Question 2

What are the working volumes that you currently

freeze?

- Less than 1 Liter

- 1 Liter to 5 Liters

- Between 5 and 20 Liters

- More than 20 Liters


Polling Question 3

To what temperature are you exposing your

material?

- Down to -30°C

- Between -31°C and -80°C

- Between -81°C and -196°C


Harvest Collection, Storage & Transport Critical Considerations

Fluid containment

Glass Transition Temperature (Freezing or

refrigerated applications)

Product integrity and stability

Thaw time/conditions

Secure Labeling and Tamper Evidence

Transportation validation

― Bag design, fill volume, support vessel and

shipping configuration

― Secant modulus

Thank you for your participation!

Thank you for your participation!

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