A new dimension in single use cell culture performance
When working with cell culture, there are many critical parameters to determine: the selection of culture media, the optimization of cell culture conditions, and most importantly, the avoidance of contamination. Pall understands these process requirements and has developed a novel single-use bioreactor system that allows users to focus on optimizing the application rather than on the mechanics of bioreactor installation and operation.
CELL CULTURE SOLUTIONS
Pall has a comprehensive portfolio of advanced single-use solutions for cell culture applications
Biocontainer and baffled tote with square design and bottom mounted, large format impeller with direct mechanical connection to drive motor
Excellent mixing and mass transfer characteristics, efficient for either upflow or downflow operations
Biocontainer packaging integrates tubing, filters, and aseptic connectors in foam inserts; color coded connections to system utilities (air, sensor and liquid lines)
Packaging protects biocontainer during transport and facilitates rapid installation
Biocontainer designed with 9 liquid feed ports, headspace and direct media spare ports, up to 4 conventional probe ports, 2 sampling ports, 2 vents with integrated filters, ring sparger, gas overlay and open pipe sparger
Fully configurable biocontainer suitable for production operations from simple batch to complex fed batch applications
Full function process controller with graphical user interface, 4 thermal mass flow controllers, 4 pumps, PID control for key process parameters (temperature, pH, dissolved oxygen), software 21 CFR 11 capable
Very easy operation in production environments, fully capable for GMP environment operations and easy compliance with electronic batch records and documentation requirements
Controller software with OPC capability
Choice of turnkey operation or integration into site level supervisory and control systems, with full 21 CFR 11 capability in either mode
The Allegro STR 200 single-use bioreactor has been developed and tested for mammalian cell culture for the production of biopharmaceuticals and vaccines. Typical applications include:
Culture of suspension cells
Seed expansion for larger scale bioreactors
Pilot scale production
Production for clinical trials
With all product contact surfaces being single-use components, the demands on maintenance, such as cleaning and cleaning validation, are minimal. This makes single-use bioreactors the first choice for flexible manufacturing sites, as found in process development, vaccine production or CMO plants.
The special format of the Allegro STR 200 single-use bioreactor offers excellent mixing and gas transfer and provides an ideal environment for mammalian cells. The cell growth rates and viabilities confirm that the Allegro STR 200 bioreactor is an excellent platform for mammalian cell culture in the pharmaceutical industry. Allegro film is qualified per USP <87> Biological Reactivity Tests, in vitro (MEM cytotoxicity) and has been demonstrated to be free of known cytotoxic leachables such as bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP).
The Allegro STR 200 single-use bioreactor is designed for working volumes between 60 and 200 liters. The biocontainer is mounted on load cells to measure the exact amount of liquid that is added into the reactor and for automated filling and dosing. The temperature in the bioreactor is controlled with a heater. It has enough heat transfer capacity to heat a full 200 liter load within 12 hours from 4 °C to 37 °C. The controller will automatically regulate the temperature to the required set point.
Ease of Installation
In many of the current single-use bioreactors designs, there is risk of damage to the bioreactor bag during transportation and installation. It is therefore very important that the bag is properly packaged and the interaction of the operator with the equipment is well defined. Pall has performed an industrial design study to optimize packaging and set-up of the bioreactor.
Pall has optimized the procedures for installing the biocontainer into the bioreactor and running the cell culture. On the inside of the bioreactor door a pictographic guide leads the operator through all steps to setup and connect the biocontainer to the controller. All connections are clearly identified with color tags and labels and numbered in the order of installation, ensuring simple, quick set-up. The components that are mounted to the top of the biocontainer remain in their foam packaging until the biocontainer is fully inflated to avoid any damage on the bioreactor system. Sensors verify the critical operations and actuate locks once certain checkpoints are met.
The Allegro STR 200 single-use bioreactor is delivered as a turn-key system. The controller maintains four peristaltic pumps to control liquid addition into the biocontainer during the reactor run. Sensors can be connected to monitor the cell culture run and record the data in a batch protocol. The controller has a well-structured user interface and maintains all the controls to run operations according to the US Code of Federal Regulations (21 CFR, Part 11).
All user interaction can be performed on the ergonomic color touch screen interface, which is integrated into the controller. The interface is well structured and offers quick access to all relevant functions. This proven user interface design is common to all current Pall automated systems.
Data transfer and automation
The user interface has all the technical features as required in 21 CFR 11. A separate document is available that lists all the requirements and explains how they were solved on the Allegro STR 200 bioreactor. The collected batch data can be manually transferred via USB flash memory. With the in-built OPC server it is also possible to collect the batch data automatically with any SCADA system during the reactor operation.
One of the key components in the Allegro STR 200 single-use bioreactor is the Allegro STR 200 biocontainer. It is made of the same fully transparent, low extractables film as all other Allegro processing systems. The biocontainers are 100% integrity tested in manufacturing. Due to the unique self-expanding design of the Allegro biocontainer, there is no need for the operator to manually adjust the position of the biocontainer inside the reactor during installation, further reducing the risk of damaging the biocontainer during use. All ports and connections are labelled with color number tags, providing guidance on how to set up and connect the biocontainer to the hardware.
Impeller and Sparger Assembly
As in the range of Allegro single-use mixers, the impeller seal housing is mounted at the bottom of the biocontainer. It connects the single-use impeller to the bioreactor motor. The ring sparger is mounted around it. There are three gas lines connected to the impeller and sparger assembly, one providing sterile gas to the ring sparger, another providing sterile gas to the open pipe sparger (optional) and the third allowing a seal leak test for the mechanical seals on the impeller seal housing.
All tubing and equipment on the Allegro STR 200 biocontainer can be customized to fit the exact needs of your process. The biocontainer is equipped with all needed connection ports:
1 gas overlay inlet that is usually equipped with a sterilizing grade gas filter
2 vent ports that are usually equipped with heated sterilizing grade vent filters
1 gas inlet to the ring sparger that is usually equipped with a sterilizing grade filter
1 gas inlet to the open pipe sparger that is usually equipped with a sterilizing grade filter
9 ports for liquid addition into the biocontainer
1 port for the temperature sensor
4 ports for aseptic insertion of conventional sensors
2 sample ports
1 bottom drain port
Pall's single-use systems design team will help design the right biocontainer setup that fits your needs.
The Allegro STR 200 single-use bioreactor has been developed according to the latest GMP guidelines and is manufactured and tested to the Pall quality system. It has been designed for GMP production.
The Allegro STR 200 bioreactor is delivered with complete documentation. The documentation contains the hardware descriptions, instructions for use and a set of certificates for the initial test work and calibration.
A Validation Guide is available for the Allegro STR 200 bioreactor. The Validation Guide covers all the basic validation work that Pall has performed on the bioreactor system. It also contains guidance on how to qualify the bioreactor.
Pall also provides an on-site qualification service, using a prepared set of documents that allow a relatively simple qualification that is fully compliant to GAMP. Following recent GMP guideline recommendations, a full qualification run (OQ1) on the first manufactured systems has been performed. Customers will receive copies of the procedures and results of this qualification run, meaning they need only repeat a shorter qualification (OQ2) on the installed bioreactor.
Electronic Records (21 CFR 11)
The Allegro STR 200 bioreactor controller offers all the technical features that are required to run the system compliant to 21 CFR 11. An administrator can set up users and define user rights and passwords. The passwords safety complies with the requirement in 21 CFR 11 for electronic signatures. The electronic records are saved in a protected format and options for backup to external systems are available. The controller also offers an OPC interface to fully control the operations on the bioreactor from an external SCADA system.
Preventive Maintenance and Service Offerings
The Allegro STR 200 single-use bioreactors are well supported with extensive servicing offers. Pall has a global network of technicians and engineers available to assist with qualification, installation, training, technical support up to preventive maintenance and on-site repairs.
Cell Culture Performance
The Allegro STR 200 single use bioreactor brings a new dimension to cell culture processes. Pall has taken extra care during the development of the bioreactor to optimize it for mammalian cell culture. The baffled cubical design features excellent mixing and makes maximal use of the bioreactor footprint for cell culture volumes from 60 to 200 liters. The hard mounted, large bottom impeller accounts for fast mixing times at low impeller speed. The whole design allows very high cell densities and viabilities in both batch and fed-batch cell cultures.
One of the key features of a bioreactor for mammalian cell culture is excellent mixing at relatively low impeller speed. The large pitch-blade impeller achieves excellent mixing without having a negative impact on cell viability.
The Allegro STR 200 single-use bioreactor offers both gas additions through a sparger or as overlay. It allows users to achieve very high k La values that are ideal for mammalian cell culture.