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.
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.
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.
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.
Figure 1. Mustang XT5000 chromatography capsules are modular and easily plug together for high capacity systems or multi-step
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.
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.