October 18-21, 2015
Currently, biocompatibility assays based on USP Class VI or ISO 10993 standards are known to be unsuitable for evaluating the impact of SU technologies on biopharmaceutical processes. Although growth inhibiting substances like bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP) have been present in raw materials of plastics, this specific substance has not been identified until recently (Hammond et al,. 2013) due to the insensitivity of commonly used cell lines. Up to today, the majority of plastic materials used in single-use containers for cell cultivation or media applications do not have the level of raw material control which is needed to ensure batch-to-batch consistency.
While a cell line and corresponding media system has been identified that can detect detrimental concentrations of bDtBPP (DECHEMA study, R. Eibl et al., 2014) it is has been unclear if this system is capable to detect other growth inhibiting substances as well. Therefore, cytotoxic substances that impact DNA replication and the cellular energy metabolism have been tested on several lines, including cell lines recommended for cytotoxicity studies and CHO cell lines for biopharmaceutical production. Data presented showing the impact on cell growth and viability of those cell lines. Based on this data a recommendation for a cell based raw material test is given, providing a suitable screening tool for unknown cell affecting compounds
Eike Jurkiewicz and Alexander Tappe, "Assessing cell lines for cell growth assays as alternative for existing cytotoxicity assays" 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). https://dc.engconfintl.org/biopoly/39