IMPACT OF TUBING ON PROCESS FLUIDS
The primary concern for the tubing's impact on process fluids are biocompatibility, leachables, adsorption–absorption, and
permeability of gas and light (particularly ultraviolet light). Biocompatibility is typically assessed by applying the USP
Biological Reactivity Tests to the tubing material after a "worst case" sterilization process, either in vivo (<87>, cytotoxicity) (2), or in vitro for Class VI (<88>, implantable) plastics (3). Other standard tests may include pyrogenicity. Recommended standard reference
tests for tubing are described in the BPSA component quality test matrices guide (4).
Potential leachables are initially assessed by considering extractables determined under exaggerated process conditions, such
as higher temperatures, more aggressive solvents, and longer contact times. The maximum sterilization process conditions should
also be included (typically >125 °C steam autoclave or 50 kGy gamma irradiation) because these factors can increase the level
of process leachables from some tubing. Similarly, the impact of heat welding on leachables should also be included in extractables
assessments. For more information on determination of tubing extractables data, see the 2008 and 2010 BPSA extractables guides
Adsorption, where target molecules bind to tubing contact surfaces, is a primary concern with protein molecules, but the relative
smallsurface area to volume ratio typically limits protein concentration losses to only highly dilute solutions. Absorption,
where target molecules migrate into the tubing solid phase itself, are a greater concern with small molecules such as preservatives,
which are generally limited to final formulations, but should be assessed for tubing used at that stage of the process. Low
permeability tubing (for gases and light) can also provide reduced absorption of small molecules.
Although particles in tubing used in upstream processes (media, buffers and intermediates) upstream of filters have not been
a major concern, applying single-use systems to aseptic vaccine manufacturing or in post-filtration formulation and filling
of biopharmaceuticals has raised concerns about the potential impact of particles from tubing fill lines on final dosages.
Extrusion of tubing is generally a low particle-generating process, but handling, cutting, joining, and environmental conditions
for single-use system assembly can have an impact. Particle levels from tubing in systems used downstream of final filtration
should be considered in critical applications.