Disposables Solve Tomorrow's Manufacturing Problems

A large chromatography membrane capsule, a multi-component system, and a new aseptic connector can be applied to widen manufacturing bottlenecks.
Jul 01, 2005
Volume 18, Issue 7

Disposable technology has been used effectively as a process solution for over 25 years and new uses and applications are constantly being developed. The key to all applications is the ability to pre-sterilize components and systems with gamma radiation and package them against contamination.

Disposable (or single-use) processing provides a number of benefits, such as elimination or reduction of cleaning and cleaning validation; reduction of cross-contamination risk; less operator error; and minimization of capital expenditures and space requirements. Each of these advantages benefit drug companies differently. For example, biotech start-ups are seeking to avoid capital costs associated with hard-piped systems, while the use of disposables helps contract manufacturers eliminate cross-contamination.

Ian Sellick
Disposable technologies also deliver unique benefits to specific drug manufacturing processes. The expected surge in FDA-approved large-molecule drugs, like gene therapies and cancer vaccines, looms ominously over predictions for a manufacturing capacity crunch beginning around 2008. This article addresses some of the latest developments in disposables technology.

HIGH-CAPACITY CHROMATOGRAPHY Traditional chromatography technologies used to capture and polish macromolecules are inefficient. A new ion-exchange chromatography membrane-capsule has been developed which is more convenient, more reliable, and quicker to use compared with chromatography resins because it is provided in a unit that does not require any packing of media. Ion-exchange chromatography membranes are known for their ability to polish (remove) large molecules at high dynamic flowrates, but they have not been available in the high-capacity range needed to perform large-scale capture (bind and elute) steps.

Figure 1. Mustang XT5000 chromatography capsules are modular and easily plug together for high capacity systems or multi-step processes.
The new 5-L membrane capsule (Mustang XT5000) removes contaminants such as DNA, viruses, endotoxins, and host cell proteins from product feeds (Figure 1). It enables good resolution with high yields and minimal elution volumes for capture of large biomolecules due to characteristics of the membrane, a uniform flow path, and the low ratio of total volume to membrane volume. The capsule is ideal for new drugs and therapies that utilize recombinant proteins, plasmids, and other viral vectors as well as blood plasma fractions.

Ion-exchange membrane chromatography allows biomolecules to access all binding sites by direct fluid convection. Because the binding is not diffusion limited, high dynamic binding and sharp breakthrough curves are achieved over a wide range of flowrates and molecular sizes. By contrast, resin chromatography is limited due to the speed with which large molecules diffuse through the pore structure of the media. Capital investments in hard-piped columns, coupled with the recurring expense of resins, column packing, cleaning, and cleaning validation make this chromatography method very costly when compared to membrane capsules.

MULTI-COMPONENT ASSEMBLIES Disposable technologies are available for virtually every aspect of biopharmaceutical manufacturing and can be bundled into pre-assembled, pre-sterilized systems. The benefits of disposable processing multiply as single-use technologies expand from stand-alone devices to multi-component assemblies.

Multi-component disposable systems are used for filtration, clarification, purification, and separation applications for numerous vaccines, monoclonal antibodies, and other therapies. Disposable components used in these systems include wide-ranging configurations of direct flow filtration (DFF) filters, tangential flow filtration (TFF) cassettes, chromatography membrane capsules, depth filters, aseptic connection devices, tubing, adaptors, clamps, and bags. These systems can be supplied pre-sterilized (by gamma irradiation) and pre-assembled to eliminate the need for sterilization and sterilization validation procedures. This reduces maintenance costs of sterilization equipment as well as time and labor associated with validation documentation. These bundled solutions can literally be taken out of the box and placed onto the manufacturing floor, reducing the potential for cross-contamination and operator exposure to hazardous biological materials.

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