The Challenges of Adopting Single-Use Technology

Insights on single-use systems implementation and exploitation in biopharmaceutical manufacturing and processing, based on a QbD approach.
Nov 02, 2012

During the past three decades, single-use technology (SUT) has evolved many fold. From its origins with filter housings and bioprocess containers to today, disposable process applications practically cover the entire spectrum of biopharmaceutical manufacturing, from cell banking to fill/finish (1, 2). It's of interest to consider a commonly used industry definition for single-use systems (SUS) as defined by the Bio-Process Systems Alliance: "Single-use systems consist of fluid path components to replace reusable stainless steel components. The most typical systems are made up of bag chambers, connectors, tubing and filter capsules. For more complex unit operations such as cross flow filtration or cell culture, the single-use systems will include other functional components such as agitation systems, and single-use sensors" (3).

This is a basic definition, and in practice, should be modified to take into account other simple systems, including bottles, syringes, pipettes, and culture flasks such as rollers, T-flasks, and erlenmeyers. Nevertheless, it remains a straightforward reminder of what SUS are.

The application of this technology for the manufacture of biopharmaceuticals represents a major technology innovation in the 21st century and can bring a number of advantages, such as:

  • improvements in process, operational efficiency, and throughput
  • avoidance of cross contamination
  • avoidance of sterilization-in-place (SIP) and cleaning-in-place (CIP) processes and their validation
  • favorable or reduced capital investment
  • faster facility set-up time (4).

It's important to examine the shift in process paradigm surrounding SUS. Traditional multi-use biotech processes use fixed stainless-steel upstream and downstream systems of various sizes in fixed facilities that can take three to four years to build and start (1, 5). The change of process paradigm with SUS means that their inherent flexibility and impact on plant design, exploited together with a just-in-time production and supply-chain approach, as part of a manufacturing strategy will likely render some classical production philosophies obsolete (5, 6). It's not surprising that industry surveys are projecting that the trend towards adoption of SUT will continue, with rapid growth in this market (7).

While SUS are innovative, they cannot always provide an acceptable manufacturing strategy at a full industrial scale. For example, for monoclonal antibodies (mAbs), single-use bioreactors (SUBs) of 2000 L are available and "off the shelf" and fully integrated plants at a similar scale such as the KUbio (GE Healthcare) integrated concept are offered by one large supplier (8, 9). Nevertheless, a number of hurdles still stand in the way of larger scale SUS, such as component design and/or the risk of failure where the single-use bag lacks structural integrity or suffers easily from fissures or pinholes created during deployment. For these reasons, it seems likely that stainless-steel systems will remain as the large-scale production tool (10–16000 L).

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