Single-Use Still News
Disposable processing continues to provide versatility and ease-of-use for downstream operations. “Turning around existing purification equipment faster is critical to eliminating capacity constraints and bottlenecks,” says Paul Chapman, vp for downstream processing at Millipore. “Increasing the facility’s total throughput means not spending an inordinate amount of time on cleaning and validation steps.”
Recent advances extending the reach of disposables from upstream operations to clarification and chromatography, and even to viral filtration and final formulation, put upstream “on the road to realizing a fully disposable purification process, at least for the 2–3 kg scale.”
Millipore’s single-use product line reflects the versatility and scale of which Chapman speaks. The company’s Mobius FlexReady line combines single-use filters and assemblies with process-ready hardware platforms for media/buffer prep, clarification, tangential flow filtration (TFF), and virus filtration. FlexReady products allow users to install equipment, configure applications, and validate processes quickly from development-scale through small-scale commercial manufacturing, he adds.
Watching disposables make their way into relatively complex downstream unit operations is encouraging. Tangential flow (also called crossflow) filtration (TFF) is a preferred method for concentrating protein solutions, buffer exchanges, and fractionation by molecular weight. Where normal flow filtration directs fluids into the membrane under pressure, TFF works by pumping the process fluid across the membrane surface. Lower fouling in TFF comes at the cost of a recirculation loop.
Earlier this year Pall obtained the rights to a new type of TFF, single-pass TFF (SPTFF), from SPF Innovations (spfinnovations.com). Pall claims the technique provides high concentration factors and high recovery. And, while it is not yet available in fully disposable format, SPTFF caused considerable stir at its debut at “Interphex 2009”, according to the company.
SPTFF operates similarly to TFF, but instead of concentrating through one membrane, product is transferred to sequential membranes where it becomes progressively more concentrated. Thus SPTFF eliminates the recirculation loop, reduces mixing or foaming issues, and has lower hold-up volumes for easier recovery.
SPTFF allows for in-line processing and easier integration with other process steps, for example, chromatography and in-line concentration. Residence times are on the order of minutes vs. several hours for conventional TFF, which generates lower shear exposure and enables operation at elevated temperature to reduce viscosity, reports marketing director Ian Sellick. “SPTFF is a derivation of a technology that everybody uses, but in a more functionally simple format that saves significant costs.”
Dr. Grund goes so far as to call the deployment and integration of disposables the big downstream processing story over the past 12 months. “There has been a good deal of discussion recently on when fully disposable downstream equipment makes sense, and when stainless steel might be more appropriate.”
GE’s ReadyToProcess™ line of disposable equipment includes the Wave disposable bioprocess Cellbag™, packed ready to use chromatography columns, filters, membranes, tubing and connectors. Also in this product line are ÄKTA™ready preparative chromatography systems built for process scale-up and production for early clinical phases. These systems operate with ready-to-use, disposable flow paths.
ReadyToProcess is based on the emerging need among bioprocessors, at least at small and mid-sized scales, for agility and flexibility—plug and play is the term GE applies. Not all the equipment needs to be disposable. “You probably would not want to use all the components only once, but even where you don’t you can at least plug them in rather quickly,” Dr. Grund says.