Product description
Single-use bioreactor bags are disposable cell-culture vessels designed for upstream pharmaceutical and biotechnology processes. They provide the sterile product-contact environment required for inoculation, feeding, aeration, sampling, monitoring and harvesting without a reusable stainless steel culture vessel forming the primary fluid-contact surface.
Configurations are available for both rocking-mode and stirred-tank bioreactor systems, covering process development, seed train expansion and larger-scale manufacturing applications.
Depending on the bioreactor platform, bags can incorporate optical pH and dissolved-oxygen sensors, gas sparging, exhaust filtration, thermowells, sampling lines, feed and harvest tubing and optional cell-retention components for perfusion processes.
Technical overview
Rocking bioreactor bags are designed for installation on a rocking platform where the movement of the tray generates mixing and gas transfer within the flexible bag. Standard nominal bag volumes include 2 L, 10 L, 20 L and 50 L.
Stirred-tank single-use bioreactor bags are designed for larger-scale cultivation and incorporate dedicated aeration, sensor and process-line interfaces. Configurations cover nominal volumes from approximately 50 L to 2,000 L.
Both concepts can be configured around different cultivation strategies, including seed expansion, batch, fed-batch and suitable perfusion processes.
Operating principle
Rocking-mode bioreactor bags
The flexible bioreactor bag is installed on a compatible rocking platform. Controlled rocking motion creates wave-induced circulation within the liquid, providing mixing and supporting gas transfer without a conventional internal stirred-tank impeller.
Rocking bags are particularly suited to smaller upstream volumes, seed train expansion and applications where a compact single-use culture system is preferred.
Configurations can range from a basic fluid-path design to systems with integrated optical pH and dissolved-oxygen sensors. Perfusion configurations can additionally incorporate a cell-retention membrane.
Stirred-tank bioreactor bags
Stirred-tank bioreactor bags are installed inside a compatible vessel or support system and provide the disposable product-contact surface for large-scale cell culture.
Gas is introduced through integrated sparging elements while dedicated process lines provide inoculation, feed, sampling and harvest functions. Exhaust gas is handled through a filtered exhaust line.
Integrated pH and dissolved-oxygen measurement interfaces support process monitoring, while a thermowell provides a dedicated temperature-measurement interface.
Material options
The bioreactor bags are manufactured from a multilayer bioprocess film developed for cell-culture applications requiring mechanical strength, biocompatibility and compatibility with gamma sterilisation.
The exact proprietary film formulation is configuration-specific and should be confirmed as part of the technical documentation for the selected bioreactor bag.
Additional fluid-path materials can include pharmaceutical-grade tubing, polymer fittings, sensor interfaces, filters and connection components selected according to the bioreactor configuration.
Available micron ratings
Not applicable to the bioreactor bag itself. The flexible bag is a cell-culture vessel rather than filtration media and therefore does not have a filtration micron rating.
Stirred-tank configurations use dedicated gas-sparging elements. Available aeration-hole sizes include:
- 20 µm micro-sparging
- 0.5 mm macro-sparging
- 1 mm macro-sparging
These dimensions relate to aeration rather than liquid filtration.
Perfusion configurations can also incorporate a cell-retention membrane. Membrane selection should be specified separately according to the cell line, cultivation mode and required retention performance.
Design and construction
Rocking-mode configurations
Standard rocking-mode bags are available in:
- 2 L nominal volume
- 10 L nominal volume
- 20 L nominal volume
- 50 L nominal volume
| Nominal bag volume | Minimum working volume | Maximum working volume |
|---|---|---|
| 2 L | 0.2 L | 1 L |
| 10 L | 1 L | 5 L |
| 20 L | 2 L | 10 L |
| 50 L | 5 L | 25 L |
Three principal rocking-mode configurations are available:
- Basic: standard process lines without integrated pH or dissolved-oxygen sensors.
- Process monitoring: configuration with integrated optical pH and dissolved-oxygen sensors.
- Perfusion: process-monitoring configuration with an additional integrated cell-retention membrane.
Optical pH and dissolved-oxygen monitoring
Suitable rocking configurations can incorporate optical pH and dissolved oxygen measurement.
| Parameter | Control range | Measurement range |
|---|---|---|
| pH | 6.0–8.0 | 4.5–8.5 |
| Dissolved oxygen | 0–100% | 0–250% |
Perfusion configurations
Rocking bioreactor bags can be configured for perfusion culture using an integrated cell-retention membrane.
This enables continuous or semi-continuous removal of spent medium while retaining cells within the culture system. External hollow-fiber retention concepts can also be considered depending on the process.
Stirred-tank configurations
Stirred-tank single-use bioreactor bags are available across a scale range from approximately 50 L to 2,000 L.
Standard configurations incorporate process interfaces for:
- Cell inoculation
- Media and nutrient feeding
- Sampling
- Product harvest
- Gas inlet and sparging
- Filtered exhaust
- pH measurement
- Dissolved-oxygen measurement
- Temperature measurement
Aeration and sparging
Stirred-tank configurations use dedicated aeration elements for gas delivery into the culture.
Available sparging concepts include combinations of micro- and macro-sparging, with standard aeration-hole dimensions of 20 µm, 0.5 mm and 1 mm.
Sparger configuration and distribution are selected according to bioreactor scale and process requirements such as oxygen transfer, carbon-dioxide stripping, shear sensitivity and cell density.
Process monitoring
Stirred-tank configurations incorporate pH and dissolved-oxygen measurement interfaces. Depending on vessel size, multiple sensor interfaces can be used to support process monitoring.
A thermowell is also incorporated for process-temperature measurement.
Pressure and exhaust management
Suitable configurations can incorporate a single-use pressure sensor and dedicated filtered exhaust line.
Additional backup filtration or exhaust-port configurations can be included where required by the process design.
Sterilisation and supply condition
Single-use bioreactor bags are supplied sterile and ready for installation into the compatible bioreactor system.
Standard configurations are sterilised using gamma irradiation in the 25–45 kGy range and are individually protected using double-layer PE packaging.
Quality and documentation
The available bioreactor bags are manufactured under ISO Class 7 cleanroom conditions and each bag is integrity tested prior to release.
Available conformity and quality documentation can include:
- USP <788> Particulate Matter
- USP <87> Cytotoxicity
- USP <88> Biological Reactivity
- USP <85> bacterial endotoxin information
- FDA 21 CFR 177–182 material conformity information
- Animal-derived component-free material statements
- TSE / BSE documentation
- Certificate of Analysis / Certificate of Quality
- Bag integrity test documentation
- Gamma sterilisation documentation
- Validation documentation where applicable
Exact conformity and validation documentation should be confirmed for the selected bioreactor platform and fluid-path configuration.
Typical applications
- Seed train expansion
- Batch cell culture
- Fed-batch cell culture
- Perfusion cell culture
- Suspension cell culture
- Adherent cell culture
- CHO cell culture
- HEK293 cell culture
- BHK21 cell culture
- Hybridoma culture
- SF9 insect-cell culture
- Vero cell culture
- Monoclonal antibody production
- Vaccine manufacturing
- Cell and gene therapy processes
- Upstream process development
- Commercial upstream manufacturing
Key benefits
- Multiple bioreactor platforms: rocking-mode and stirred-tank bag configurations support different upstream scales and cultivation strategies.
- Scale range from development to manufacturing: rocking bags cover small upstream volumes while stirred-tank configurations extend to approximately 2,000 L.
- Integrated process monitoring: suitable configurations incorporate pH and dissolved-oxygen sensors.
- Perfusion capability: rocking bags can incorporate an integrated cell-retention membrane.
- Controlled aeration: stirred-tank configurations provide dedicated micro- and macro-sparging options.
- Complete process fluid path: inoculation, feeding, sampling, harvest and exhaust lines can be incorporated into the disposable assembly.
- Pre-sterilised: standard configurations are gamma irradiated and supplied ready for use.
- Single-use processing: the disposable product-contact system reduces reliance on cleaning and sterilisation of a reusable primary culture vessel.
Configuration and quotation
Bioreactor bag selection should begin with the bioreactor platform and required working volume rather than nominal bag size alone.
For technical configuration and quotation, provide the following information where available:
- Rocking-mode or stirred-tank bioreactor platform
- Existing bioreactor equipment where applicable
- Nominal bag volume
- Minimum working volume
- Maximum working volume
- Cell line
- Suspension or adherent culture
- Batch, fed-batch or perfusion process
- Expected cell density
- Required oxygen-transfer performance
- CO₂ stripping requirement
- Shear-sensitivity considerations
- pH sensor requirement
- Dissolved-oxygen sensor requirement
- Perfusion or cell-retention requirement
- Required feed lines
- Sampling configuration
- Harvest configuration
- Required tubing and connectors
- Required conformity and validation documentation
- Prototype or qualification quantity
- Estimated annual demand
Where an existing bioreactor platform is already in use, equipment model, required working volume and existing bag specification provide the best starting point for technical review.