Processing pharmaceuticals and other materials requiring sterile conditions poses complex and seemingly contradictory demands on mixing technology. Equipment should avoid threats of contamination while affording easy cleaning and simple set-up and minimizing downtime for validation and process engineering. In addition, mixers should provide high output from a small footprint.
Vendors are meeting these challenges in a variety of ways. A couple are particularly focusing on single-use, i.e., disposable, mixing systems, which represent one of the biggest growth areas.
For instance, GE Healthcare, Chalfont St. Giles, U.K. and Piscataway, N.J., touts its Wave Bioreactor single-use system as virtually eliminating the need for cleaning and validation while avoiding cross-contamination (www.ChemicalProcessing.com/articles/2006/017.html).
Materials to be mixed only contact a pre-sterilized disposable bag mounted on a special rocking platform (Figure 1). Its motion induces waves in the fluid that provide mixing and gas transfer.
The technology is used extensively in fermentation processes -- including for production of monoclonal antibodies and viruses, insect cell culture and cGMP manufacturing. Scales range from bench-top systems as small as 100-ml to production-scale units of 500-l working volume.
However, the bag is quite complex due to the need for aeration, inoculation, sampling and acid/base addition. So GE now has launched a simpler single-use bag for basic liquid mixing applications. The M Bag does away with the need for a mixing tank or a conventional mixer and, like the Wave Bioreactor, also obviates cleaning, sterilization and validation. The bags, which range in size from 20-l to 600-l, come with a large screw-cap port for the easy addition of powders and other solids, as well as fill and sample lines. They also can be customized to suit an end user's individual processes. If larger-scale more-aggressive mixing is required, GE offers versions with a built-in impeller.
Demand also is growing for more sensing technologies.The company already offers dissolved oxygen, pH, carbon dioxide and oxygen sensors via miniature fiber-optic microprobes. "The ultimate goal here would be to integrate every probe that you might want in the bag to give all the required data in real-time. Going forward, there is a lot of interest in RFID too, as the wireless format makes everything much easier for operators," says Rich Ferraro, senior product manager.
While originally developed to avoid cleaning and validation issues, today the technology has evolved into a route for flexible manufacturing. "Remember that it avoids large capex [capital expenditure] and the hardware is generally off-the-shelf, too," he notes.
Ferraro believes that some innovations developed for use by bioprocessing and pharmaceutical companies eventually will find their way into mainstream chemical processing as the focus there also shifts to more flexible manufacturing techniques.
"In chemicals processing you run into issues that you don't see in bioprocessing -- for example, the different fluid viscosities and solids loadings as seen in slurries. There is only so much shear force or energy input that a disposable impeller or Wave format can do in these situations before you run into performance issues," he admits. "We'll need a more elegant yet cost-effective solution going forward for the fine chemical or small molecule industries and some companies are already working on this."