In your opinion do you think that there is another bDtBPP type compound that we haven’t identified yet or do you think the key leachables have been identified and are being addressed.

Answer

IIt is difficult to make predictions because there are many variable factors to consider, such as differences in the level of sensitivity of cell lines. In addition, the types of compounds present in a single-use assembly that have the potential to become leachables will vary from system to system and are highly dependent upon the materials of construction used in the assembly and the processing conditions they have been exposed to. That being said, it is possible to make some predictions of what compounds may be extracted from a given material based upon the chemical composition. For example, the films used in single-use bioprocess assemblies are often composed of several layers of polymers, such as polyethylene, polyester, nylon, and ethylene vinyl alcohol copolymers. Small molecule additives may be needed for processing and performance. Some common types of additives include antioxidants and slip agents. In addition, residual monomers and chemical degradants resulting from film processing may also remain in the film and have the potential to be extracted. The information provided by supplies about the materials of construction and the extractables profile for a single-use system can be leveraged to assess the potential structure-activity relationship for the chemical compounds and the specific cell line being used. Over the past several years, we at GE Healthcare have advanced our understanding of the film chemistry that affects cell growth and have expanded our supply chain management strategy to allow us to better trace the composition of our films. We have taken substantial steps in our scientific evaluation of films, combining the chemical and physical attribute testing with cell culture growth performance. For example, the Bioclear™ 11 film used in WAVE Cellbag™ bioreactors has been designed to have a low antioxidant profile for better compatibility with certain sensitive cell lines.