Single-Use Solutions

The increasing popularity of “single-use” or disposable bioreactors for upstream processing can be understood by considering a typical biotechnology manufacturing facility. The infrastructure required to implement traditional glass/steel bioreactors is substantial, and the time and expense required to validate it can be significant. The requirement that both the bioreactor itself and its ingress and egress tubing use inert materials such as 316-L electropolished stainless steel results in a large capital investment and long lead times for components. In addition to mitigating the capital cost of steel systems, single-use systems bring the additional benefits of shorter preparation and sterilization times, lower purified water volumes for cleaning vessels between growth runs, and significantly reduced maintenance times. Additionally, single-use bioreactors and the associated plastic tubing lend themselves to being reconfigured and validated quickly and efficiently as manufacturing or process requirements change, allowing end users to build flexible multiproduct facilities.

Whether a single-use bioreactor is a “rocker” (e.g., GE/Wave Biotech) or “stirred-tank” (e.g., Thermo Scientific/HyClone, XCellerex, ATMI/Artellis) system, its basic function remains to provide a controlled environment for optimal growth and product formation by organisms present in the growth medium. To that end, a measurement and automation system is required to provide stable (or well-controlled changes in) process parameters such as pH, dissolved oxygen, temperature, pressure, agitation rate, as well as liquid and gas handling.

Disposable sensors can be preinserted into a single-use bioreactor bag and gamma irradiated with the bag so the entire system arrives sterile and the time from unpacking the bag to inoculation is minimized. Single-use sensors having RFID tags that contain relevant calibration parameters minimize operator time and the risk of sensor breakage or a sterility breach during insertion into the bag. Today, disposable sensors for dissolved oxygen, temperature, and pressure measurements are becoming common; robust, disposable pH and cell density sensors are expected to be available by 2009.

Automation systems used with disposable bioreactors must be highly reconfigurable to adapt to the different processes that can be run in a single system. Furthermore, these automation systems must be user friendly and plug-and-play, with a wide variety of external equipment such as pumps, scales, and offline analyzers. Ideally, an automation system should allow rapid scalability of a process through advanced process models and smart algorithms as well as ease of data collection and analysis. As more companies involved in bioprocessing realize that they can scale their ideas into clinical production but choose to outsource their manufacturing, the automation system must also allow for process technology transfer between different facilities and types of reactors.

As the average titer (measured in grams of product per liter of culture, g/L) produced continues to increase, the size of bioreactor vessels required in manufacturing will decrease. This trend will further accelerate the transition to single-use bioreactors in production environments. With adoption of fully disposable facilities, the advent of scalable bioprocesses (from research through GMP manufacturing) is imminent.