Today, nearly 97% of biopharmaceutical manufacturers use single-use technologies.1 Not only are manufacturers implementing single-use technologies, but also the range of applications for which these technologies
are being used is expanding. Single-use technologies are now being implemented for critical steps involving direct product
contact. This gives new importance to the way these technologies are selected, implemented, and used. Issues of qualification,
validation, and sterilization have greater implication when entire product batches are at stake.
The following are answers to several questions that broadening implementation of single-use technologies has raised among
biopharmaceutical manufacturers. These questions and answers also provide an accurate view of the limits and benefits of single-use
processing, and insight into the future direction of this processing paradigm.
Hélène Pora, PhD
Q Where are single-use technologies currently being used in biopharmaceutical processing?
A Single-use technologies have traditionally been used for small-scale buffer filtration, media preparation, and storage. Recent
innovations have made a wider range of single-use technologies available for most downstream purification applications and
production scales. These include mixing technologies, cell culture bioreactors, membrane and column chromatography, tangential
flow filtration systems, and formulation and filling technologies.
Q What are the limits in scale of operation?
A Single-use technologies are now common in full-scale production operations, and range in size from just a few milliliters
to several thousand liters. Disposable bioprocess bags can accommodate up to approximately 3,000 L of fluid and disposable
bioreactors have been used for production purposes up to 500 L of cell culture.
Although not all single-use technologies are fully scaleable, a growing number are being introduced for use in commercial
production. Advances in disposable membrane chromatography are pushing this technology beyond pilot-scale applications into
commercial production. Even at commercial scale, however, single-use technologies may have capacity limitations. The 3,000–L
bioprocess bags are one example. As non-rigid containers, both their integrity and ability to be handled beyond this size
come into question.
Q What are the limits of operating pressure and temperature associated with single-use systems?
A Single-use systems can withstand comparatively less pressure than stainless steel systems. However, exact limits depend on
the material composition of the system and the tubing attachment method. In general, bioprocess bags and tubing cannot withstand
more than a few psi (<0.5 bar) of pressure. However, tubing can be reinforced to withstand greater pressures. Most capsule
filters can be used with up to 45 psi (3 bar) pressure and a limited few can withstand up to 90 psi (6.5 bar) pressure.
Liquid generally moves through single-use systems by way of gravity, but in some cases a peristaltic pump is also used. Although
operating pressure limits do not impact processing performance, there is a certain resistance to change in the biopharmaceutical
industry that can make addressing pressure differences more difficult.
Biopharmaceutical manufacturers also must consider the temperature limits of single-use technologies when selecting new components
and systems. Disposable components are generally suitable for standard biopharmaceutical operating temperatures, which range
between 4 and 40 °C. However, some bags, tubing, and connectors may not meet low temperature requirements for storage. Most
biopharmaceutical drugs are stored at –30 °C but some products (e.g., cells) require storage at –80 °C. It is critical that
biopharmaceutical manufacturers validate all components in the assembly to ensure that they meet the complete range of temperature
requirements. Although stainless steel systems have no temperature limitations, integral parts such as seals often do, and
therefore must be validated to temperature specifications.