New Single-Use Bioreactor Technology Emphasizes Ease-of-Use and Intelligent Process Control

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An updated bioreactor based on rocking technology has more advanced controls but is easier for biopharmaceutical manufacturers to use.

Single-use bioreactors come in all shapes and sizes that fit the variety of manufacturing conditions required for different biopharmaceutical production processes. WAVE Bioreactor technology, which was first introduced in 1996, has a unique rocking motion that provides for efficient mixing without the need for the use of internal stirrers. The industry has changed a lot in the last 17 years, though, and single-use bioreactor technology has evolved with it. To meet these changing needs of the biopharmaceutical industry, GE Healthcare Life Sciences has updated the WAVE Bioreactor system.

Changing needs
 “We realize that the biopharmaceutical industry today constantly needs to develop to meet new regulatory requirements. It also now relies on many different types of cell-culture processes and is looking to leverage advanced process analytical technology while also increasing product yield and reducing turnover time. To meet these changing needs, we have developed a new WAVE Bioreactor system that builds on the functionality of the original bioreactor but is more advanced and yet easier to use,” says Cecilia Annerén, product manager with GE Healthcare Life Sciences. “Most importantly, she adds, “we have incorporated accurate and intelligent controls for numerous process parameters, many more automated functions, and a user-friendly interface that includes several data analysis and reporting options.”

More than just rocking
The ReadyToProcess WAVE 25 single-use bioreactor system consists of a rocker, a gas mixer, and a pump, all operated by software installed on a client computer. The rocker is used together with one of three trays that support disposable bioreactor cultivation chambers with working volumes up to 25 L. As with the original WAVE Bioreactor system, the rocker provides mixing through rocking and temperature and weight measurement through integrated sensors and load cells, respectively. The gas mixer delivers gas of a defined composition to the culture and is used, together with optical sensors in the bioreactor, for online control of culture pH and dissolved oxygen (DO).


The sensors in the disposable bioreactor and the rocker are very important features of the new system, according to Annerén, because they are combined with advanced feed-back loops for the monitoring and adjustment of process parameters. The system can determine, for example, the appropriate heating rate depending on the culture mass/volume in the bioreactor, and will implement a more aggressive heating rate for large volumes. In addition, the amount of acid or base needed to maintain a particular pH level is automatically determined based on the current pH level, the molarity of the base or acid being used, the size of the tubing, and the feed rate of the pump.

In addition, the system has a new tilt position to facilitate sampling and harvest, and its rounded corners make for easier cleaning. “While the new features seem simple, they can have a big impact on the operators using the bioreactor. For example, the tilt position eliminates the need for heavy lifting when harvesting the bag, and the wide top-opening of the lid enables complicated manipulations of the bag without removing the lid,” Annerén notes. Furthermore, it is now possible to adjust the speed, angle, and motion of rocking. The latter parameter is new for the upgraded system and determines the acceleration profile, which at low settings creates a gentler wave motion that is suitable for cells on microcarriers and at higher settings creates the more aggressive waves that are required for robust cells with a higher oxygen uptake rate, according to Annerén.

Easy to use
In addition to the new design of the tray, the software that comes with the system, which was originally developed for use with GE Healthcare Life Science’s chromatography equipment, has been adapted specifically for operation of the updated rocking bioreactor and incorporates many features that are designed for user friendliness. “It was very important to us that, even though we have incorporated very advanced functionality into the new bioreactor, it continues to be extremely easy to operate, so that anyone can rapidly learn how to use it without the need for extensive training,” Annerén comments.

Therefore, the graphical interface was designed to be intuitive and provides real-time information. In addition, a library of predefined control parameters tailored for different cultivation volumes has been included so that suitable parameters can be automatically determined for a run, which can reduce the set-up time and provide accurate and stable control of the process, according to Annerén. She adds that the system can also be set up to automatically monitor reactions and respond to changing reaction conditions in order to optimize performance, and there is a method-development function that allows operators to establish automated operations, such as daily feeding at a given time. Finally, the software allows the setting of alarm conditions for any of several essential parameters (heating, gas flow, carbon dioxide pH, and DO) and can update the user with optional e-mail notifications. “Improving efficiency and productivity are primary goals for many biopharmaceutical manufacturers, and the automated features that have been incorporated into the software for the updated WAVE bioreactor are intended to help achieve these goals,” Annerén notes.

Areas of interest
While the first-generation WAVE Bioreactor has commonly been used in seed-train applications and small-scale production, there is, according to Annerén, growing interest from the process development community in the newer bioreactor. “Because it is so easy to adjust a wide variety of process parameters and monitor the changes in the culture conditions in real time, it is possible to very rapidly gather a large amount of data and evaluate the performance of a given biopharmaceutical process under numerous different conditions. As a result, process development times can be reduced, which is a major goal for all pharmaceutical manufacturers,” she observes.

Another feature of the updated system that is attracting attention for both process development and commercial manufacturing is the ability to carry out perfusion culturing easily and accurately. “Perfusion is definitely being more widely used, so we made a point of developing the new bioreactor so that perfusion can be easily achieved at many scales,” says Annerén. In fact, the optional pump can operate over a very wide range of flow rates from 0.1 L to up to 144 L per day. In addition, there is an optional autocalibration feature that enables automatic calibration of the pump flow rate if desired.