October 18-21, 2015
The fields of biopharmaceutical processing and cell therapy are adopting single-use, closed systems throughout their workflows to enhance sterility, minimize waste wash effluent and enable manufacturing flexibility compared to traditional stainless steel bioreactors. One of the key single-use technologies in use is the rocking bioreactor, comprising a polymer film bag (outfitted with ports and sensors) mounted to a tray capable of mixing the contents of the bag and a control system (controlling temperature, agitation, and potentially media perfusion).
One of the challenges encountered in rocking bioreactor bags is the fact that upon inflation/filling with media, the originally flat bioreactor bags often develop folds and dimples due to their inflated geometry. These deformations tend to be inconsequential at small volumes and low agitation rates/times, but can lead to flex fatigue failures such as whitening, delamination and through-cracking under more extreme conditions. In practice, these failures are dependent on a number of factors including bag material and volume, mounting geometry, rocking angle and rate, and the duration of culture, making a systematic study of the material properties controlling this behavior difficult and time-consuming.
Several flex fatigue testing systems exist in the literature, including Gelbo and Sonntag-Universal, but none of these effectively model the unique geometry and stresses of the rocking bioreactor geometry. To this end, we have developed accelerated test methods to analyze the flexural fatigue behavior of multilayer rocking bioreactor films. These methods enable quality control testing of film lots, and have the potential to compare different film compositions with a rapid and reproducible test, thereby facilitating development of new films.
Our test method models the local geometry surrounding the fold/dimple in a rocking bioreactor in a small sample of film, and cycles the sample to accelerate flexural fatigue at the dimple site. Initial results indicate the ability to accelerate film failure from tens of days on a rocking bioreactor platform (using a full bioreactor bag) to tens of hours using less than ten square inches of film. We will discuss the effects of various experimental parameters on film failure, optimization of test procedures and correlation with rocking bioreactor testing in the field.
Donald Buckley, K. Amanda Misner, Terry Saunders, Andrew Burns, Hongyi Zhou, Eugene Boden, Susan Burke, Ross Acucena, and Mark Roberts, "Flexural fatigue behavior of rocking bioreactor films" in "Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications", Ekta Mahajan, Genentech, Inc., USA Gary Lye, University College London, UK Eds, ECI Symposium Series, (2015). http://dc.engconfintl.org/biopoly/17