The Evolution of Single-Use Technologies in Aseptic Processing

The authors describe the origins of single-use components and explain their application to aseptic processes. They also show how disposable devices have changed over time and offer a glimpse of the future.
Apr 02, 2010
Volume 34, Issue 4

For the past decade, the development and approval of biological drugs has increased rapidly. This increase highlights the significance of aseptic processing because biologics commonly cannot be heat sterilized. Because aseptic processing receives greater regulatory scrutiny than heat sterilization does, the industry developed, in addition to risk-management and risk-analysis activities, new processing equipment and technologies to overcome potential weaknesses (1). These technologies' main purpose was the avoidance of human intervention, which is one of the most substantial risks in aseptic processing. The technologies included environmental-containment solutions such as isolators and restricted-access barrier systems, and new filling strategies such as blow–fill–seal. Disposable solutions have changed, and their applications have broadened, during the past several years.

The most far-reaching changes in the technology's early days affected processing equipment, which gradually was converted into single-use equipment (2). The benefits of single-use equipment not only enable a potentially higher sterility-assurance level within process steps than was possible before, but also enable production-utilization enhancements, cost savings, and end-user protection. Single-use equipment does not require setup times of 8–10 h or copious amounts of water for cleaning purposes (3). Furthermore, it protects end users from contact with potentially hazardous fluids. This article will focus on recent advances in single-use technologies.

The development of single-use equipment

The first disposable process parts to be used were tubing sets. They were followed by filtration devices called capsule filters. Capsule filters were only available in small effective-filtration-area units, commonly between 0.5 and 2 ft2. The introduction of single-use components for mixing and fluid containment required larger filter capsules, and end users requested small-scale pleated devices for scaling studies. These two factors led the filter-capsule range to be expanded to an area of 0.1 to 30 ft2 (4–6). Current filter capsules are gamma-sterilizable and commonly connected to tubing sets or bag assemblies (see Figure 1).

Figure 2
Single-use technology for mixing and holding tanks also emerged (e.g., single-use bag devices). Single-use bags are available in volumes of 20 to 3000 L and can replace glass vessels, carboys, and stainless-steel tanks. Before single-use bags could be introduced into the production process, they needed to demonstrate mechanical stability, chemical resistance, a barrier to oxygen transfer, and low leachable levels, even when the bags were gamma sterilized at 50 kGy. New polymeric films laminated onto each other made these characteristics possible and have become common (see Figure 2).

Single-use bags are used most often in an assembly format, either with or without a filter, as part of a multibag system. The entire assembly is gamma irradiated in the packaging and is ready to use.

Single-use systems, though, are not restricted to bags and filters. Various equipment components are available that can be combined into a single-use system or process step. Such equipment components include the following:

  • Mixing systems of various designs and volumes
  • Sensors (e.g., for dissolved oxygen, pH, and conductivity)
  • Sterile fluid-transfer connectors and tubing
  • Fluid-sampling devices
  • Bioreactors of different designs, volumes, and agitation technologies)
  • Aseptic-transfer systems for fluids and solids
  • Freeze–thaw bags
  • Ultra- and diafiltration
  • Membrane-chromatography (e.g., ion exchange) columns (7, 8)
  • Viral-clearance and ultraviolet-inactivation filters.

lorem ipsum