According to Paul Priebe, who manages process filtration and disposables at Sartorius (www.sartorius.com), “virtually all” bioprocessors are specifying or considering disposable equipment. Priebe sees the trend as part of a natural evolution, as more and more unit operations become available in disposable formats. He notes that enabling technologies, particularly membrane chromatography, sterile connecting, welding and sealing devices, aseptic agitation systems, and disposable sensors are paving the way for robust, integrated unit operations with fully disposable fluid paths that provide the benefits of disposability without sacrificing performance. Moreover, systems are evolving for complete disposability in traditionally hardware-intensive unit operations.
“This started several years ago with disposable bioreactors, but now traditional hardware and systems companies are getting into the game,” says Priebe. Sartorius recently partnered with Wave AG (www.wavebiotech.ch) to combine the Sartorius Biostat control system with a disposable, rocking bioreactor bag. The Sartorius system incorporates two disposable optical chemical sensors for pH and dissolved oxygen, both with feedback control, controllers for oxygen, nitrogen, CO2, and mass flow, and a pressure transmitter to monitor and control gas flow.
Disposables are already ubiquitous in media and buffer preparation, crossflow filtration, concentration and diafiltration, low-pH viral inactivation, and ion exchange chromatography. Disposable separations, in the form of ion exchange membrane chromatography, are fine for removing trace contaminants.
Unfortunately, disposable affinity chromatography remains elusive and probably will be for several years. One workaround may be to switch to relatively low-cost resins, for example substituting hydroxyapatite for Protein A. Developing chromatography media inexpensive enough to use only once would probably entail a tradeoff in capacity, but the trend of high protein titers, which continues unabated, creates a situation where media capacity will struggle to catch up, or keep up, with titers.
“It’s a race between capacity and titers,” says Rich Richieri, Sr. vp of manufacturing for Avid Biosciences, a subsidiary of Peregrine Pharmaceuticals (www.peregrineinc.com). And at least for now, titers are winning.
Buffer prep is the operation where disposables save the most time and generate the most economic payback for companies like Avid. In the past year the company replaced a Q resin column, which required packing, qualifying, and cleaning, with a membrane absorber. Avid is also beginning to look closely at disposable bioreactors, where the company expects to see savings equal to or greater than that for buffers. “Single-use reactors are going to be a game changer for contract manufacturers,” Richieri says. “Not just because they’re disposable, but for their impact on process footprint and facilities.”
For unit operations where single use is not economically feasible, such as affinity chromatography, Priebe believes that disposables can play a support role. Protein A affinity chromatography may be too expensive to use only once, but treating bioprocess fluids with a flow-through disposable chromatography device before the capture step dramatically increases the efficiency of Protein A media. And the column may be connected to a skid that utilizes a disposable fluid path.
“These support equipment designs will allow processors to utilize and benefit from disposables while maintaining much of the feel and control that they have had in traditional systems,” Priebe adds.
Denise DiTomasso, technical marketing manager at SAFC Biosciences (www.safcbiosciences.com), reports that while adoption of disposables in downstream processing is rising, manufacturers remain skeptical for some applications where single-use surfaces come into contact with a “live” protein. Such concerns arise, to some degree, from the relative lack of regulatory guidance on proper use of disposable equipment.
“We can demonstrate product safety to our satisfaction, but what will the FDA ask for or expect? Manufacturers are doing the best they can, but there are still many unknowns.” She cites initiatives from the Bioprocess Systems Alliance, an organization of vendors and suppliers, to develop workable guidelines. “But in the end regulatory agencies will need to provide input,” she notes. SAFC sells sterile, single-use, polyethylene process kits based on its BIOEAZE™ bags, which range in size from 1 L up to 1,000 L.