Disposable bags are widely used in the biotechnology industry. The two main purposes are to store cell-culture media and to
grow cells for inoculum or production. Several groups have reported growth inhibition resulting from the use of such products.
This report shows independent data from four companies, using several different cell lines and growth media, and suggests
a method that can be implemented for quality control at disposable-bag vendors.
Recently, a group of engineers and scientists within the cell-culture process-development community convened the first inaugural
Cell-Culture Industry Forum (CCIF), which was held in Longmont, Colorado, in February 2011. More than 30 individuals from
nine companies met over three days to present topics related to the common challenges and problems within the large-scale
cell-culture industry. A highlighted theme at the first forum was the observation of cell growth inhibition, presumably resulting
from the use of disposable bags. Disposables are widely used in the biotechnology industry for numerous bioprocessing functions.
Extractables and leachables from disposables are frequently discussed (1). Two of the functions of disposable bags in the
industry are to store cell-culture media and to grow cells within the bags at all steps of cell culture-based manufacturing.
At the meeting, as well as described in other forums (2–6), it was clear that cell growth was sometimes affected by the use
of disposables for these applications. A subteam was formed after the CCIF adjourned to further discuss and act upon these
Photo Credit: Nicholas Rigg/Getty Images
This paper describes collaboration in which four of the participating CCIF companies jointly assessed cell growth inhibition
resulting from the use of disposable cell-culture bags (hereafter referred to as bags). The assessments are meant to uncover
subtle effects on cell growth when medium is warmed in bags prior to use in cell-culture steps. Developing a widely applicable
growth test is not a trivial exercise—it should be cell line- and media-independent so that vendors can apply it with confidence
and avoid unwanted false-positive results. To that end, data are shown from these four companies, encompassing many different
cell lines grown in four independent and proprietary media in which cell growth effects are apparent when water used for media
preparation is warmed in the bags prior to use. The method described has leveraged strategies developed at each company as
part of their ongoing work in disposable-bag selection. It is implementable across bag vendors and can potentially uncover
problematic bag lots as well as identify when bag-film changes lead to inhibition of cell growth.