S62: A leachable compound in plastic bioprocess equipment that is detrimental to cell growth

The biopharmaceutical industry is rapidly moving cell culture and other upstream fluid-mixing operations out of traditional hard-piped stainless steel vessels and into plastic-lined bioreactors and plastic bags.  While this move yields many benefits, the introduction of a new set of materials into biomanufacturing processes forces the industry (and regulatory bodies) to pose new questions about the suitability of these materials. In the course of evaluating leachable compounds from plastic bioprocessing materials, we have discovered one compound, bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP), that can interfere with CHO cell culture at low concentrations (below the parts-per million range).  bDtBPP is generated by breakdown of Irgafos® 168, an antioxidant that is commonly used in polyolefin formulations. These findings, including experiments exploring the parameters that influence the formation and leaching of bDtBPP, will be discussed.